Heterogeneous reactions on the aerosol particle surface in the atmosphere play important roles in air pollution, climate change, and global biogeochemical cycles. However, the reported uptake coefficients of heterogen...Heterogeneous reactions on the aerosol particle surface in the atmosphere play important roles in air pollution, climate change, and global biogeochemical cycles. However, the reported uptake coefficients of heterogeneous reactions usually have large variations and may not be relevant to real atmospheric conditions. One of the major reasons for this is the use of bulk samples in laboratory experiments, while particles in the atmosphere are suspended individually. A number of technologies have been developed recently to study heterogeneous reactions on the surfaces of individual particles. Precise measurements on the reactive surface area, volume, and morphology of individual particles are necessary for calculating the uptake coefficient, quantifying reactants and products, and understanding the reaction mechanism better. In this study, for the first time we used synchrotron radiation X-ray computed tomography（XCT） and micro-Raman spectrometry to measure individual CaCO_3 particle morphology, with sizes ranging from 3.5–6.5 μm. Particle surface area and volume were calculated using a reconstruction method based on software threedimensional（3-D） rendering. The XCT was first validated with high-resolution fieldemission scanning electron microscopy（FE-SEM） to acquire accurate CaCO_3 particle surface area and volume estimates. Our results showed an average difference of only 6.1% in surface area and 3.2% in volume measured either by micro-Raman spectrometry or X-ray tomography. X-ray tomography and FE-SEM can provide more morphological details of individual Ca CO3 particles than micro-Raman spectrometry. This study demonstrated that X-ray computed tomography and micro-Raman spectrometry can precisely measure the surface area, volume, and morphology of an individual particle.展开更多
Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-...Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.展开更多
Arsenic speciation in freshwater fish is crucial for providing meaningful consumption guidelines that allow the public to make informed decisions regarding its consumption.While marine fish have attractedmuch research...Arsenic speciation in freshwater fish is crucial for providing meaningful consumption guidelines that allow the public to make informed decisions regarding its consumption.While marine fish have attractedmuch research interest due to their higher arsenic content,research on freshwater fish is limited due to the challenges in quantifying and identifying arsenic species present at trace levels.We describe here a sensitivemethod and its application to the quantification of arsenic species in freshwater fish.Arsenic species from fish tissues were extracted using a methanol/water mixture(1:1 vol.ratio)and ultrasound sonication.Anion-exchange high-performance liquid chromatography(HPLC)enabled separation of arsenobetaine(AsB),inorganic arsenite(iAs^(Ⅲ)),dimethylarsinic acid(DMA),monomethylarsonic acid(MMA),inorganic arsenate(iAs^(Ⅴ)),and three new arsenic species.Inductively coupled plasma mass spectrometry(ICPMS)provided highly sensitive and specific detection of arsenic.A limit of detection of 0.25μg/kg(wet weight fish tissue)was achieved for the five target arsenic species:AsB,iAs^(Ⅲ),DMA,MMA,and iAs^(Ⅴ).A series of experimentswere conducted to ensure the accuracy and validity of the analytical method.The method was successfully applied to the determination of arsenic species in lakewhitefish,northern pike,and walleye,with AsB,DMA,and iAs^(Ⅴ) being frequently detected.Three new arsenic species were detected,but their chromatographic retention times did not match with those of any available arsenic standards.Future research is necessary to elucidate the identity of these new arsenic species detected in freshwater fish.展开更多
Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity am...Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity among cancer cells,which exhibit varying degrees of metabolic reprogramming and thus may result in differential contributions to drug resistance.A home-built single-cell quantitative mass spectrometry(MS)platform,which integrates micromanipulation and electro-osmotic sampling,was developed to quantitatively profile the tricarboxylic acid(TCA)cycle metabolites at the single-cell level.Using this platform,the metabolic profiles of drug-sensitive MCF-7 breast cancer cells and their drug-resistant derivative MCF-7/ADR cells were compared.This results revealed a selective upregulation of downstream TCA cycle metabolites includingα-ketoglutarate,succinate,fumarate,and malate in drug-resistant cancer cells,while early TCA metabolites remained largely unchanged.Furthermore,notable variations in the abundance of the metabolites were observed in individual cells.The comparative analysis also revealed that not all MCF-7/ADR cells exhibit the same degree of metabolic deviation from the parental line in the metabolites during resistance acquisition.The observed metabolic profiles indicate enhanced glutaminolysis,altered mitochondrial electron transport chain activity,and increased metabolic flexibility in drug-resistant cancer cells that support their survival under chemotherapeutic stress.The findings further suggest the potential for incorporating cellular metabolic heterogeneity into future drug resistance studies.展开更多
The acidity of atmospheric aerosols influences fundamental physicochemical processes that affect climate and human health.We recently developed a novel and facilewater-probebased method for directly measuring of the p...The acidity of atmospheric aerosols influences fundamental physicochemical processes that affect climate and human health.We recently developed a novel and facilewater-probebased method for directly measuring of the pH for micrometer-size droplets,providing a promising technique to better understand aerosol acidity in the atmosphere.The complex chemical composition of fine particles in the ambient air,however,poses certain challenges to using a water-probe for pH measurement,including interference from interactions between compositions and the influence of similar compositions on water structure.To explore the universality of our method,it was employed to measure the pH of ammonium,nitrate,carbonate,sulfate,and chloride particles.The pH of particles covering a broad range(0–14)were accurately determined,thereby demonstrating that our method can be generally applied,even to alkaline particles.Furthermore,a standard spectral library was developed by integrating the standard spectra of common hydrated ions extracted through the waterprobe.The library can be employed to identify particle composition and overcome the spectral overlap problem resulting from similar effects.Using the spectral library,all ions were identified and their concentrations were determined,in turn allowing successful pH measurement of multicomponent(ammonium-sulfate-nitrate-chloride)particles.Insights into the synergistic effect of Cl^(–),NO_(3)^(–),and NH_(4)^(+)depletion obtained with our approach revealed the interplay between pH and volatile partitioning.Given the ubiquity of component partitioning and pH variation in particles,the water probemay provide a new perspective on the underlying mechanisms of aerosol aging and aerosol–cloud interaction.展开更多
The performance and price of copper-based micro linear products are determined by the diameter uniformity.How to accurately detect the wire diameter of long-length copper based micro linear products without cutting or...The performance and price of copper-based micro linear products are determined by the diameter uniformity.How to accurately detect the wire diameter of long-length copper based micro linear products without cutting or damage has always been a technical concern for production enterprises.Herein,a novel approach was developed for nondestructive detection of the average diameter at any given segment of a long copper wire by assessing the adsorption capacity of arginine on its surface.The amount of adsorbent on the surface of the copper wire exhibits a positive correlation with the area,which can be detected by extractive electrospray ionization mass spectrometry(EESI-MS)after online elution with ammonia.The experimental results demonstrated that the analysis can be completed within 15 min,with a good linear relationship between copper wires with different diameters and the adsorption capacity of arginine.The linear correlation coefficient R2was 0.995,the relative standard deviation was 1.10%-2.81%,and the detection limit reached 2.5μm(length of segment=4 cm),showing potential applications for facile measurement of the average diameter of various metal wires.展开更多
Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus,the pathological mechanism of which remains unclear yet.Disturbed lipid metabo...Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus,the pathological mechanism of which remains unclear yet.Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases.However,the lipidome signature of human myometrium,which could be crucial in the development of adenomyosis,remains unknown.In this study,we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultraperformance liquid chromatography(UPLC)coupled with triple quadrupole(QqQ)-mass spectrometry(MS).A total of 317 lipid species were successfully quantified in the myometrial tissues from women with(n=38)or without(n=65)adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital(Bejing,China).Up to 83 lipid species showed significant alternations in content between the two groups.These lipid aberrations involved multiple metabolic pathways,and emphasized inflammation,cell migration,and immune dysregulation upon adenomyosis.Moreover,receiver operating characteristic(ROC)curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve(AUC)of 0.906.Desorption electrospray ionization MS imaging(MSI)further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue.Collectively,these results extremely improved our understanding on the molecular basis of adenomyosis,and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.展开更多
RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.Howe...RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.However,to the best of our knowledge,RNA modifications in peripheral white blood cells(immune cells)have not been systematically investigated before.Here we utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS)for the quantification of 19 chemical modifications in total RNA and 17 chemical modifications in small RNA in peripheral white blood cells from breast cancer patients and healthy controls.We found out 13 RNA modifications were up-regulated in total RNA samples of breast cancer patients.For small RNA samples,only N6-methyladenosine(m^(6)A)was down-regulated in breast cancer patients(P<0.0001).Receiver operating characteristic(ROC)curves analysis showed that N4-acetylcytidine(ac^(4)C)in total RNA had an area under curve(AUC)value of 0.833,and m^(6)A in small RNA had an AUC value of 0.994.Our results further illustrated that RNA modifications may play vital roles in immune cell biology of breast cancer,and may act as novel biomarkers for the diagnosis of breast cancer.展开更多
[Objectives]This study was conducted to quickly qualitatively and quantitatively analyze the residues of 10 plant growth regulators(PGRs)in bean sprouts.[Methods]Using bean sprouts as the test material,a high-performa...[Objectives]This study was conducted to quickly qualitatively and quantitatively analyze the residues of 10 plant growth regulators(PGRs)in bean sprouts.[Methods]Using bean sprouts as the test material,a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was established to determine the residual levels of 10 PGRs in bean sprouts.[Results]Under optimized conditions,the retention time of the 10 PGRs ranged from 6.45 to 11.43 min.When the mass concentration ranged from 0.005 to 0.05μg/ml,all PGRs exhibited good linearity,with correlation coefficients(r)≥0.9991.The limits of detection(LODs,S/N=3)were in the range of 0.30-0.92μg/kg,and the limits of quantification(LOQs)were in the range of 0.50-2.10μg/kg.The average recovery values at three concentration levels ranged from 80%to 105.8%,with relative standard deviations(RSD s,n=6)of 2.8%-7.5%.[Conclusions]This method is simple and accurate,and provides technical reference for food safety monitoring.展开更多
[Objective]The paper aimed to effectively reduce the occurrence of bacterial resistance associated with breeding practices and to mitigate food safety risks by controlling the illegal use of veterinary drugs in self-f...[Objective]The paper aimed to effectively reduce the occurrence of bacterial resistance associated with breeding practices and to mitigate food safety risks by controlling the illegal use of veterinary drugs in self-formulated feed at the source.[Method]A screening database comprising 274 illegally added chemical drugs in self-formulated feed was established utilizing ultra-performance liquid chromatography coupled with quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(HPLC-Q-Exactive Focus/MS).Subsequently,253 batches of self-formulated feed samples from various farms in Hebei Province were screened and quantitatively analyzed.[Result]The screening results indicated the presence of 8 pharmaceutical components across 10 batches of self-formulated feed samples,with a detection rate of 3.2%and concentrations ranging from 0.06 to 28851.8μg/g.[Conclusion]The application of high-resolution mass spectrometry is feasible and highly significant for the risk monitoring of illegally added drugs in self-formulated feed.展开更多
[Objectives]This study was conducted to establish a detection method for the simultaneous determination of 18 perfluorinated compounds(PFCs)in milk tea by ultra-high performance liquid chromatography-tandem mass spect...[Objectives]This study was conducted to establish a detection method for the simultaneous determination of 18 perfluorinated compounds(PFCs)in milk tea by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS).[Methods]The samples were first subjected to precipitation of proteins by potassium ferrocyanide solution and zinc acetate solution,and then extracted by acetonitrile and detected by LC-MS/MS.Next,sodium chloride was added,and after vortex centrifugation,the acetonitrile layer was dried by blowing with nitrogen.Subsequently,1 ml of methanol was added to prepare a test solution.An ACQUITY UPLC BEH C18(2.6 m,2.1 mm×100 mm)chromatographic column was used for liquid phase separation,and gradient elution was performed using 10 mmol ammonium acetate solution-acetonitrile as the mobile phase.The MS detection adopted the MRM mode for acquisition,positive and negative ion mode switching for simultaneous determination,and external standard method for quantification.[Results]In the linear ranges of the target substances,the correlation coefficients R^(2)were all greater than 0.99.The detection limits of the method was in the range of 0.001-0.05μg/kg,and the quantitation limits were in the range of 0.03-0.20 ng/L.The recovery values ranged from 72.8%to 110.5%.[Conclusions]This method has high sensitivity and good accuracy,and thus strong practical value.展开更多
Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this...Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this article,the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry(TC-ESI-MS^(n))is applied to investigate interactions between ubiquitin and two flavonol molecules,respectively.The combination of collision-induced dissociation(CID)and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges.While structural changes of proteins disturbed by small molecules are unseen in ESI-MS^(n),TC-ESI-MS^(n)allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions,meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data,and the characteristics of structural intermediates.展开更多
Proteins are indispensable to all biological systems and drive life processes through activities that are intricately linked to their three-dimensional(3D)structures.Traditional proteomics often provides static snapsh...Proteins are indispensable to all biological systems and drive life processes through activities that are intricately linked to their three-dimensional(3D)structures.Traditional proteomics often provides static snapshots of protein expression,leaving unanswered questions about how proteins respond to stimuli and affect cellular functions.Limited proteolysis coupled with mass spectrometry(LiP-MS)has emerged as a powerful technique for exploring protein structure and function under near-natural conditions.Studies have revealed that LiP-MS is invaluable for structural and functional proteomics because it offers novel insights into protein dynamics.In this review,we summarise the current applications of LiP-MS in diverse areas such as the discovery and identification of drug targets,metabolite action mechanisms,proteome dynamics,protein interactions,and disease biomarkers.We also address the critical challenges in ongoing research and discuss their broader implications for advancing our understanding of protein biology and drug discovery.LiP-MS holds significant promise for accelerating biomarker and therapeutic target development as well as advancing molecular biology research in animals,plants,and microorganisms.展开更多
BACKGROUND Cardiovascular disease(CVD)and associated sequalae remain the leading cause of disability worldwide.Ischemic heart disease(IHD)and heart failure are the most common etiologies of morbidity and mortality wor...BACKGROUND Cardiovascular disease(CVD)and associated sequalae remain the leading cause of disability worldwide.Ischemic heart disease(IHD)and heart failure are the most common etiologies of morbidity and mortality worldwide.This is due to the poor diagnostic and management methods for heart failure and IHD.Early detection of related risk factors through modern strategies is underestimated and requires further research.AIM To interpret data from the published literature on volatile organic compounds(VOC),including all the methods used to analyze exhaled breath in patients with IHD and heart failure.METHODS Searches for specific keywords were performed on Scopus and PubMed.A total of 20 studies were identified in breath analysis and IHD and heart failure.The study is registered in PROSPERO(Registration No.CRD42023470556).RESULTS Considering the articles found,more research is required to gain a full understanding of the role of VOCs in IHD and heart failure.However,the existing literature demonstrates that cardiac metabolic changes can be expressed in exhaled air.The number of papers found is extremely low,making interpretation extremely difficult.CONCLUSION Exhaled breath analysis can be a novel biomarker for the diagnosis and prevention of heart failure and IHD.Exhaled breath analysis can be used as a mirror to reflect the metabolic changes related to IHD and heart failure.展开更多
Polygonati rhizoma is often used in Chinese medicine and as food.In this study,atmospheric pressure matrixassisted laser desorption ionization and quadruple-time-of-flight(MALDI-Q-TOF)mass spectrometry techniques were...Polygonati rhizoma is often used in Chinese medicine and as food.In this study,atmospheric pressure matrixassisted laser desorption ionization and quadruple-time-of-flight(MALDI-Q-TOF)mass spectrometry techniques were applied to P.rhizoma samples from Polygonatum cyrtonema Hua species.Positive ions were mainly detected in the mass range of m/z 200-600,while negative ions were mainly observed in the mass range of m/z 100-450.A total of 263 components were identified and the spatial distribution and changes in saccharides contents during the steaming process of P.rhizoma were investigated.Monosaccharide and disaccharide exhibit a relatively uniform distribution,while the oligosaccharides were mainly found in the bast of fresh P.rhizoma.Although the contents of monosaccharide and disaccharide were increased during steaming,that of trisaccharide,tetrasaccharide,and pentasaccharide were decreased.We used the 5 saccharide types with the greatest variation in content as variables for the principal component analysis(PCA)and cluster analysis.Both PCA and cluster analysis showed that these 5 saccharides can be used as markers in the steaming process of the P.rhizoma.Present study of mass spectrometry imaging provides novel insights into the spatiotemporal accumulation patterns of saccharides in P.rhizoma,improving our understanding of the steaming process.展开更多
The investigation of reaction kinetics is the key to understanding the nature of reaction processes.However,monitoring fast photochemical reactions by mass spectrometry remains challenging.Herein,we developed an optic...The investigation of reaction kinetics is the key to understanding the nature of reaction processes.However,monitoring fast photochemical reactions by mass spectrometry remains challenging.Herein,we developed an optical focusing inductive electrospray(OF-iESI)mass spectrometry platform for real-time and in-situ photoreaction monitoring.Coaxial irradiation from back of nanoelectrospray emitter with a taper section was utilized,so the emitter could act as optical lens to help achieving much larger optical power density at emitter tip compared to other sections,which allowed for in-situ reaction monitoring of photoreactions.Through theoretical calculations,the highest optical power density region volume was ca.45 nL.We also integrated a controller for the laser source(450 nm),enabling the modulation of pulse duration(>1 ms).This facilitates the study of photochemical reaction kinetics.The in-situ capability of this device was proved by capturing the short-lived photogenerated intermediates during the dehydrogenation of tetrahydroquinoline.This device was further used to investigate the kinetics of triplet energy transfer based Paternò-Büchi reaction.The reaction order has hitherto remained undetermined while the result of OF-iESI suggested it followed pseudo-second-order reaction kinetics.The short-lived donor-acceptor collision complex intermediate was also successfully identified by tandem mass spectrometry.展开更多
OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-perfo...OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Network pharmacology was employed was integrated with UPLC-Q-TOF-MS to predict SZF targets for the treatment of UAN,which were subsequently validated through in vivo experiments.Sixty male Bagg Albino Laboratory-Bred Mouse,substrain c mice were randomly allocated into six groups:Normal,Model,Febuxostat,and three SZF dosage groups.Except for the Normal group,all mice were administered potassium oxonate(250 mg/kg)and adenine(50 mg/kg)via gavage to induce UAN.Four hours postadministration,the Febuxostat group received Febuxostat(6 mg/kg),while the SZF groups received low(0.234 g/kg),medium(0.468 g/kg),or high(0.936 g/kg)doses of SZF.The Normal and Model groups were given an equivalent volume of saline.All treatments were conducted over a period of four weeks.Urine and blood samples were collected for biochemical analysis,and kidney tissues were subjected to histopathological examination and Western blot analysis.RESULTS:Nine prototype compounds and 30 metabolites were identified in SZF serum.Network pharmacology analysis revealed 195 drug targets and 1608 disease targets,with 76 common drug-disease targets,including signal transducer and activator of transcription 3(STAT3),proto-oncogene tyrosine-protein kinase Src(SRC),matrix metalloproteinase-9(MMP9),Caspase 3,and toll-like receptor 4(TLR4)as key targets.Gene Ontology analysis identified 325 biological processes,48 cellular components,and 72 molecular functions,while Kyoto Encyclopedia of Genes and Genomes analysis identified 113 pathways.Molecular docking demonstrated strong binding affinities between active compounds and their targets.In the animal study,SZF treatment alleviated pathological damage and improved serum and urine biochemical markers compared to the Model group(P<0.05,P<0.01,P<0.001).Western blot analysis showed a significant reduction in phosphorylated-STAT3,phosphorylatedSRC,MMP9,TLR4,and Caspase3 expression in renal tissues of SZF-treated mice(P<0.001).CONCLUSION:SZF may exert therapeutic effects on UAN through multiple targets and pathways.展开更多
Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce th...Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.展开更多
The escalating diversity of per-and polyfluoroalkyl substances(PFAS),arising from both intentional synthesis and inadvertent generation and release,has led to increasingly complex environmental PFAS compositions.In re...The escalating diversity of per-and polyfluoroalkyl substances(PFAS),arising from both intentional synthesis and inadvertent generation and release,has led to increasingly complex environmental PFAS compositions.In recent years,unknown PFAS have been frequently identified in the environment.However,the structural diversity and lack of corresponding reference standards pose significant challenges for the detection and identification of PFAS.Traditional targeted screening methods are often inadequate for detecting these compounds,making nontargeted analysis(NTA)using high-resolution mass spectrometry(HRMS)essential for identifying unknown or suspected contaminants.Nevertheless,existing NTA techniques still face limitations in comprehensively characterizing the full spectrum of PFAS in the environment.Continuous optimization and development of sample preparation methods,instrumental analytical techniques,data processing algorithms,and software are gradually expanding the coverage of NTA for diverse PFAS.This review summarizes recent advances in HRMS-based NTA methodologies for PFAS,encompassing sample preparation,separation techniques,HRMS instrument and data acquisition modes,PFAS screening strategies,and NTA data processing approaches.Furthermore,the review discusses the current challenges and prospects of PFAS NTA,such as an in-depth exploration of gas chromatography-HRMS(GC-HRMS)applications in NTA,and the utilization of machine learning(ML)models for efficient processing of complex NTA datasets.Addressing these challenges will significantly enhance the accuracy and efficiency of PFAS identification in the environment,providing a scientific basis for the regulation and control of PFAS in the future.展开更多
BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extend...BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extended period to address hypertension,with the syndrome known as Yin deficiency and Yang hyperactivity syndrome(YDYHS)frequently observed in individuals with elevated blood pressure.This syndrome is characterized by symptoms including dizziness,tinnitus,irritability,and insomnia,which are thought to result from an imbalance between Yin,representing the cooling and nourishing aspects,and Yang,denoting the active and warming aspects of the body.Despite the prevalent application of TCM in clinical settings,the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.AIM To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry(GC-MS)to elucidate the distinctive blood metabolite pattern in this patient population.METHODS GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls.Chemometric methods,including principal component analysis and partial least squares discriminant analysis,were employed to identify potential biochemical patterns.Simultaneously,the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways.Using variable importance in projection and receiver operating characteristic curve analyses,potential biomarkers were extracted to assess their clinical utility.RESULTS Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers(4-hydroxybenzoic acid,pectin,1,2,3-trihydroxybenzene,D-ribose,3-hydroxybutyric acid,quinic acid,L-lysine,oleic acid,2-hydroxybutyric acid,linoleic acid,citric acid,alpha-tocopherol,D-glucuronic acid,glycerol,N-acetyl-L-aspartic acid,betamannosylglycerate,indolelactic acid,L-glutamic acid,D-maltose,L-aspartic acid)and four metabolic pathways(linoleic acid metabolism;alanine,aspartate and glutamate metabolism;D-glutamine and D-glutamate metabolism;arginine biosynthesis).The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls.The area under the curve values ranged from 0.750 to 0.866.Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.CONCLUSION The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group,highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients.These findings may serve as an important material basis for understanding the occurrence and development of the disease,providing a scientific foundation for future clinical diagnosis.展开更多
基金supported by the Chinese Ministry of Science and Technology(No.2008AA062503)the National Natural Science Foundation Committee of China(Nos.41421064,20637020)the China Postdoctoral Science Foundation(No.20100470166)
文摘Heterogeneous reactions on the aerosol particle surface in the atmosphere play important roles in air pollution, climate change, and global biogeochemical cycles. However, the reported uptake coefficients of heterogeneous reactions usually have large variations and may not be relevant to real atmospheric conditions. One of the major reasons for this is the use of bulk samples in laboratory experiments, while particles in the atmosphere are suspended individually. A number of technologies have been developed recently to study heterogeneous reactions on the surfaces of individual particles. Precise measurements on the reactive surface area, volume, and morphology of individual particles are necessary for calculating the uptake coefficient, quantifying reactants and products, and understanding the reaction mechanism better. In this study, for the first time we used synchrotron radiation X-ray computed tomography（XCT） and micro-Raman spectrometry to measure individual CaCO_3 particle morphology, with sizes ranging from 3.5–6.5 μm. Particle surface area and volume were calculated using a reconstruction method based on software threedimensional（3-D） rendering. The XCT was first validated with high-resolution fieldemission scanning electron microscopy（FE-SEM） to acquire accurate CaCO_3 particle surface area and volume estimates. Our results showed an average difference of only 6.1% in surface area and 3.2% in volume measured either by micro-Raman spectrometry or X-ray tomography. X-ray tomography and FE-SEM can provide more morphological details of individual Ca CO3 particles than micro-Raman spectrometry. This study demonstrated that X-ray computed tomography and micro-Raman spectrometry can precisely measure the surface area, volume, and morphology of an individual particle.
基金supported by the Natural Science Foundation of Hubei Provincial Department of Education(D20232101)Shandong Second Medical University 2024 Affiliated Hospital(Teaching Hospital)Scientific Research Development Fund Project(2024FYQ026)+3 种基金the innovative Research Programme of Xiangyang No.1 People’s Hospital(XYY2023ZY01)Faculty Development Grants of Xiangyang No.1 People’s Hospital Affiliated to Hubei University of Medicine(XYY2023D05)Joint supported by Hubei Provincial Natural Science Foundation and Xiangyang of China(2025AFD091)Traditional Chinese Medicine Scientific Research Project of Hubei Provincial Administration of Traditional Chinese Medicine(ZY2025D019).
文摘Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.
基金supported by Alberta Health,Alberta Innovates,the Canada Research Chairs Program,the Canadian Institutes of Health Research,and the Natural Sciences and Engineering Research Council of Canada。
文摘Arsenic speciation in freshwater fish is crucial for providing meaningful consumption guidelines that allow the public to make informed decisions regarding its consumption.While marine fish have attractedmuch research interest due to their higher arsenic content,research on freshwater fish is limited due to the challenges in quantifying and identifying arsenic species present at trace levels.We describe here a sensitivemethod and its application to the quantification of arsenic species in freshwater fish.Arsenic species from fish tissues were extracted using a methanol/water mixture(1:1 vol.ratio)and ultrasound sonication.Anion-exchange high-performance liquid chromatography(HPLC)enabled separation of arsenobetaine(AsB),inorganic arsenite(iAs^(Ⅲ)),dimethylarsinic acid(DMA),monomethylarsonic acid(MMA),inorganic arsenate(iAs^(Ⅴ)),and three new arsenic species.Inductively coupled plasma mass spectrometry(ICPMS)provided highly sensitive and specific detection of arsenic.A limit of detection of 0.25μg/kg(wet weight fish tissue)was achieved for the five target arsenic species:AsB,iAs^(Ⅲ),DMA,MMA,and iAs^(Ⅴ).A series of experimentswere conducted to ensure the accuracy and validity of the analytical method.The method was successfully applied to the determination of arsenic species in lakewhitefish,northern pike,and walleye,with AsB,DMA,and iAs^(Ⅴ) being frequently detected.Three new arsenic species were detected,but their chromatographic retention times did not match with those of any available arsenic standards.Future research is necessary to elucidate the identity of these new arsenic species detected in freshwater fish.
基金supported by National Natural Science Foundation of China(22374080,22174068,21722504)Primary Research&Development Plan of Jiangsu Province(BK20221303,BE2022796)+1 种基金Open Foundation of State Key Laboratory of Reproductive Medicine(SKLRM-2022BP1,JX116GSP20240507)Science and Technology Development Fund of NJMU(NJMUQY2022003)。
文摘Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity among cancer cells,which exhibit varying degrees of metabolic reprogramming and thus may result in differential contributions to drug resistance.A home-built single-cell quantitative mass spectrometry(MS)platform,which integrates micromanipulation and electro-osmotic sampling,was developed to quantitatively profile the tricarboxylic acid(TCA)cycle metabolites at the single-cell level.Using this platform,the metabolic profiles of drug-sensitive MCF-7 breast cancer cells and their drug-resistant derivative MCF-7/ADR cells were compared.This results revealed a selective upregulation of downstream TCA cycle metabolites includingα-ketoglutarate,succinate,fumarate,and malate in drug-resistant cancer cells,while early TCA metabolites remained largely unchanged.Furthermore,notable variations in the abundance of the metabolites were observed in individual cells.The comparative analysis also revealed that not all MCF-7/ADR cells exhibit the same degree of metabolic deviation from the parental line in the metabolites during resistance acquisition.The observed metabolic profiles indicate enhanced glutaminolysis,altered mitochondrial electron transport chain activity,and increased metabolic flexibility in drug-resistant cancer cells that support their survival under chemotherapeutic stress.The findings further suggest the potential for incorporating cellular metabolic heterogeneity into future drug resistance studies.
基金supported by the National Natural Science Foundation of China(No.91844000)China Postdoctoral Science Foundation(No.2020M670048).
文摘The acidity of atmospheric aerosols influences fundamental physicochemical processes that affect climate and human health.We recently developed a novel and facilewater-probebased method for directly measuring of the pH for micrometer-size droplets,providing a promising technique to better understand aerosol acidity in the atmosphere.The complex chemical composition of fine particles in the ambient air,however,poses certain challenges to using a water-probe for pH measurement,including interference from interactions between compositions and the influence of similar compositions on water structure.To explore the universality of our method,it was employed to measure the pH of ammonium,nitrate,carbonate,sulfate,and chloride particles.The pH of particles covering a broad range(0–14)were accurately determined,thereby demonstrating that our method can be generally applied,even to alkaline particles.Furthermore,a standard spectral library was developed by integrating the standard spectra of common hydrated ions extracted through the waterprobe.The library can be employed to identify particle composition and overcome the spectral overlap problem resulting from similar effects.Using the spectral library,all ions were identified and their concentrations were determined,in turn allowing successful pH measurement of multicomponent(ammonium-sulfate-nitrate-chloride)particles.Insights into the synergistic effect of Cl^(–),NO_(3)^(–),and NH_(4)^(+)depletion obtained with our approach revealed the interplay between pH and volatile partitioning.Given the ubiquity of component partitioning and pH variation in particles,the water probemay provide a new perspective on the underlying mechanisms of aerosol aging and aerosol–cloud interaction.
基金supported by the National Natural Science Foundation of China(No.22422402)National Key Research and Development Program of China(No.2022YFF0705300)Key Research and Development Program of Jiangxi Province(No.20232BBG70004)。
文摘The performance and price of copper-based micro linear products are determined by the diameter uniformity.How to accurately detect the wire diameter of long-length copper based micro linear products without cutting or damage has always been a technical concern for production enterprises.Herein,a novel approach was developed for nondestructive detection of the average diameter at any given segment of a long copper wire by assessing the adsorption capacity of arginine on its surface.The amount of adsorbent on the surface of the copper wire exhibits a positive correlation with the area,which can be detected by extractive electrospray ionization mass spectrometry(EESI-MS)after online elution with ammonia.The experimental results demonstrated that the analysis can be completed within 15 min,with a good linear relationship between copper wires with different diameters and the adsorption capacity of arginine.The linear correlation coefficient R2was 0.995,the relative standard deviation was 1.10%-2.81%,and the detection limit reached 2.5μm(length of segment=4 cm),showing potential applications for facile measurement of the average diameter of various metal wires.
基金supported by the National High Level Hospital Clinical Research Funding,China(Grant Nos.:2022-PUMCH-A-204 and 2022-PUMCH-C-031)the National Natural Science Foundation of China(Grant No.:82274336).
文摘Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus,the pathological mechanism of which remains unclear yet.Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases.However,the lipidome signature of human myometrium,which could be crucial in the development of adenomyosis,remains unknown.In this study,we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultraperformance liquid chromatography(UPLC)coupled with triple quadrupole(QqQ)-mass spectrometry(MS).A total of 317 lipid species were successfully quantified in the myometrial tissues from women with(n=38)or without(n=65)adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital(Bejing,China).Up to 83 lipid species showed significant alternations in content between the two groups.These lipid aberrations involved multiple metabolic pathways,and emphasized inflammation,cell migration,and immune dysregulation upon adenomyosis.Moreover,receiver operating characteristic(ROC)curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve(AUC)of 0.906.Desorption electrospray ionization MS imaging(MSI)further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue.Collectively,these results extremely improved our understanding on the molecular basis of adenomyosis,and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.
基金supported by National Natural Science Foundation of China(Nos.21927810,22336004 and 22176167).
文摘RNA modifications play vital regulatory roles in biological systems.Dysregulated RNA modifications themselves or their regulators are associated with various diseases,including cancers and immune related diseases.However,to the best of our knowledge,RNA modifications in peripheral white blood cells(immune cells)have not been systematically investigated before.Here we utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS)for the quantification of 19 chemical modifications in total RNA and 17 chemical modifications in small RNA in peripheral white blood cells from breast cancer patients and healthy controls.We found out 13 RNA modifications were up-regulated in total RNA samples of breast cancer patients.For small RNA samples,only N6-methyladenosine(m^(6)A)was down-regulated in breast cancer patients(P<0.0001).Receiver operating characteristic(ROC)curves analysis showed that N4-acetylcytidine(ac^(4)C)in total RNA had an area under curve(AUC)value of 0.833,and m^(6)A in small RNA had an AUC value of 0.994.Our results further illustrated that RNA modifications may play vital roles in immune cell biology of breast cancer,and may act as novel biomarkers for the diagnosis of breast cancer.
基金Supported by Outstanding Talent Development Program of Hebei ProvinceTangshan Talent Funding Project(A202202005).
文摘[Objectives]This study was conducted to quickly qualitatively and quantitatively analyze the residues of 10 plant growth regulators(PGRs)in bean sprouts.[Methods]Using bean sprouts as the test material,a high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method was established to determine the residual levels of 10 PGRs in bean sprouts.[Results]Under optimized conditions,the retention time of the 10 PGRs ranged from 6.45 to 11.43 min.When the mass concentration ranged from 0.005 to 0.05μg/ml,all PGRs exhibited good linearity,with correlation coefficients(r)≥0.9991.The limits of detection(LODs,S/N=3)were in the range of 0.30-0.92μg/kg,and the limits of quantification(LOQs)were in the range of 0.50-2.10μg/kg.The average recovery values at three concentration levels ranged from 80%to 105.8%,with relative standard deviations(RSD s,n=6)of 2.8%-7.5%.[Conclusions]This method is simple and accurate,and provides technical reference for food safety monitoring.
基金Supported by the Earmarked Fund for Hebei Agriculture Research System(HBCT2024260407)。
文摘[Objective]The paper aimed to effectively reduce the occurrence of bacterial resistance associated with breeding practices and to mitigate food safety risks by controlling the illegal use of veterinary drugs in self-formulated feed at the source.[Method]A screening database comprising 274 illegally added chemical drugs in self-formulated feed was established utilizing ultra-performance liquid chromatography coupled with quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(HPLC-Q-Exactive Focus/MS).Subsequently,253 batches of self-formulated feed samples from various farms in Hebei Province were screened and quantitatively analyzed.[Result]The screening results indicated the presence of 8 pharmaceutical components across 10 batches of self-formulated feed samples,with a detection rate of 3.2%and concentrations ranging from 0.06 to 28851.8μg/g.[Conclusion]The application of high-resolution mass spectrometry is feasible and highly significant for the risk monitoring of illegally added drugs in self-formulated feed.
基金Supported by Natural Science Foundation of Hunan Province(2024JJ8266).
文摘[Objectives]This study was conducted to establish a detection method for the simultaneous determination of 18 perfluorinated compounds(PFCs)in milk tea by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS).[Methods]The samples were first subjected to precipitation of proteins by potassium ferrocyanide solution and zinc acetate solution,and then extracted by acetonitrile and detected by LC-MS/MS.Next,sodium chloride was added,and after vortex centrifugation,the acetonitrile layer was dried by blowing with nitrogen.Subsequently,1 ml of methanol was added to prepare a test solution.An ACQUITY UPLC BEH C18(2.6 m,2.1 mm×100 mm)chromatographic column was used for liquid phase separation,and gradient elution was performed using 10 mmol ammonium acetate solution-acetonitrile as the mobile phase.The MS detection adopted the MRM mode for acquisition,positive and negative ion mode switching for simultaneous determination,and external standard method for quantification.[Results]In the linear ranges of the target substances,the correlation coefficients R^(2)were all greater than 0.99.The detection limits of the method was in the range of 0.001-0.05μg/kg,and the quantitation limits were in the range of 0.03-0.20 ng/L.The recovery values ranged from 72.8%to 110.5%.[Conclusions]This method has high sensitivity and good accuracy,and thus strong practical value.
基金supports by the National Natural Science Foundation of China(No.22174037)the Joint Funds of the Hunan Provincial Natural Science Foundation of China(No.2023JJ50255)+1 种基金Changsha Science and Technology Project(No.Z202269490128)National Key Research and Development Program of China(No.2023YFF0613400)are appreciated.
文摘Traditional electrospray ionization tandem mass spectrometry(ESI-MS^(n))has been a powerful tool in diverse research areas,however,it faces great limitations in the study of protein-small molecule interactions.In this article,the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry(TC-ESI-MS^(n))is applied to investigate interactions between ubiquitin and two flavonol molecules,respectively.The combination of collision-induced dissociation(CID)and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges.While structural changes of proteins disturbed by small molecules are unseen in ESI-MS^(n),TC-ESI-MS^(n)allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions,meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data,and the characteristics of structural intermediates.
基金supported by the National Natural Science Foundation of China(Grant No.:22304002).
文摘Proteins are indispensable to all biological systems and drive life processes through activities that are intricately linked to their three-dimensional(3D)structures.Traditional proteomics often provides static snapshots of protein expression,leaving unanswered questions about how proteins respond to stimuli and affect cellular functions.Limited proteolysis coupled with mass spectrometry(LiP-MS)has emerged as a powerful technique for exploring protein structure and function under near-natural conditions.Studies have revealed that LiP-MS is invaluable for structural and functional proteomics because it offers novel insights into protein dynamics.In this review,we summarise the current applications of LiP-MS in diverse areas such as the discovery and identification of drug targets,metabolite action mechanisms,proteome dynamics,protein interactions,and disease biomarkers.We also address the critical challenges in ongoing research and discuss their broader implications for advancing our understanding of protein biology and drug discovery.LiP-MS holds significant promise for accelerating biomarker and therapeutic target development as well as advancing molecular biology research in animals,plants,and microorganisms.
基金Supported by the Government Assignment to Philipp Kopylov,No.1023022600020-6Russian Science Foundation Grant to Philipp Kopylov,No.24-15-00549the Ministry of Science and Higher Education of the Russian Federation within the Framework of State Support for the Creation and Development of World-Class Research Center to Basheer Marzoog and Peter Chomakhidze,No.075-15-2022-304.
文摘BACKGROUND Cardiovascular disease(CVD)and associated sequalae remain the leading cause of disability worldwide.Ischemic heart disease(IHD)and heart failure are the most common etiologies of morbidity and mortality worldwide.This is due to the poor diagnostic and management methods for heart failure and IHD.Early detection of related risk factors through modern strategies is underestimated and requires further research.AIM To interpret data from the published literature on volatile organic compounds(VOC),including all the methods used to analyze exhaled breath in patients with IHD and heart failure.METHODS Searches for specific keywords were performed on Scopus and PubMed.A total of 20 studies were identified in breath analysis and IHD and heart failure.The study is registered in PROSPERO(Registration No.CRD42023470556).RESULTS Considering the articles found,more research is required to gain a full understanding of the role of VOCs in IHD and heart failure.However,the existing literature demonstrates that cardiac metabolic changes can be expressed in exhaled air.The number of papers found is extremely low,making interpretation extremely difficult.CONCLUSION Exhaled breath analysis can be a novel biomarker for the diagnosis and prevention of heart failure and IHD.Exhaled breath analysis can be used as a mirror to reflect the metabolic changes related to IHD and heart failure.
基金funded by the Science and Technology Innovation Program of Hunan Province(2022RC1224,2022ZYC010)the Changsha Science and Technology Program(kh2004018)the Training Program for Excellent Young Innovators of Changsha(kq2206064)。
文摘Polygonati rhizoma is often used in Chinese medicine and as food.In this study,atmospheric pressure matrixassisted laser desorption ionization and quadruple-time-of-flight(MALDI-Q-TOF)mass spectrometry techniques were applied to P.rhizoma samples from Polygonatum cyrtonema Hua species.Positive ions were mainly detected in the mass range of m/z 200-600,while negative ions were mainly observed in the mass range of m/z 100-450.A total of 263 components were identified and the spatial distribution and changes in saccharides contents during the steaming process of P.rhizoma were investigated.Monosaccharide and disaccharide exhibit a relatively uniform distribution,while the oligosaccharides were mainly found in the bast of fresh P.rhizoma.Although the contents of monosaccharide and disaccharide were increased during steaming,that of trisaccharide,tetrasaccharide,and pentasaccharide were decreased.We used the 5 saccharide types with the greatest variation in content as variables for the principal component analysis(PCA)and cluster analysis.Both PCA and cluster analysis showed that these 5 saccharides can be used as markers in the steaming process of the P.rhizoma.Present study of mass spectrometry imaging provides novel insights into the spatiotemporal accumulation patterns of saccharides in P.rhizoma,improving our understanding of the steaming process.
基金financially supported by the National Natural Science Foundation of China(Nos.22104112 and 22374110)the Fundamental Research Funds for the Central Universities。
文摘The investigation of reaction kinetics is the key to understanding the nature of reaction processes.However,monitoring fast photochemical reactions by mass spectrometry remains challenging.Herein,we developed an optical focusing inductive electrospray(OF-iESI)mass spectrometry platform for real-time and in-situ photoreaction monitoring.Coaxial irradiation from back of nanoelectrospray emitter with a taper section was utilized,so the emitter could act as optical lens to help achieving much larger optical power density at emitter tip compared to other sections,which allowed for in-situ reaction monitoring of photoreactions.Through theoretical calculations,the highest optical power density region volume was ca.45 nL.We also integrated a controller for the laser source(450 nm),enabling the modulation of pulse duration(>1 ms).This facilitates the study of photochemical reaction kinetics.The in-situ capability of this device was proved by capturing the short-lived photogenerated intermediates during the dehydrogenation of tetrahydroquinoline.This device was further used to investigate the kinetics of triplet energy transfer based Paternò-Büchi reaction.The reaction order has hitherto remained undetermined while the result of OF-iESI suggested it followed pseudo-second-order reaction kinetics.The short-lived donor-acceptor collision complex intermediate was also successfully identified by tandem mass spectrometry.
基金National Science Foundation of China:Mechanistic Study on How Shizhi Fang Promotes Mitocytosis of Renal Tubular Epithelial Cells to Alleviate Hyperuricemia-Induced Kidney Injury(82274415)National Science Foundation of China:Mechanistic Study on Shizhi Fang in Lowering Uric Acid Based on Extracellular Signal-regulated Kinases 1 and 2-mediated Transcriptional Regulation of the Uric Acid Transporter Urate Transporter 1(82474434)。
文摘OBJECTIVE:To elucidate the potential mechanisms of Shizhi Fang(SZF,矢志方)in the treatment of uric acid nephropathy(UAN).METHODS:SZF-containing serum was prepared from six male rats and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Network pharmacology was employed was integrated with UPLC-Q-TOF-MS to predict SZF targets for the treatment of UAN,which were subsequently validated through in vivo experiments.Sixty male Bagg Albino Laboratory-Bred Mouse,substrain c mice were randomly allocated into six groups:Normal,Model,Febuxostat,and three SZF dosage groups.Except for the Normal group,all mice were administered potassium oxonate(250 mg/kg)and adenine(50 mg/kg)via gavage to induce UAN.Four hours postadministration,the Febuxostat group received Febuxostat(6 mg/kg),while the SZF groups received low(0.234 g/kg),medium(0.468 g/kg),or high(0.936 g/kg)doses of SZF.The Normal and Model groups were given an equivalent volume of saline.All treatments were conducted over a period of four weeks.Urine and blood samples were collected for biochemical analysis,and kidney tissues were subjected to histopathological examination and Western blot analysis.RESULTS:Nine prototype compounds and 30 metabolites were identified in SZF serum.Network pharmacology analysis revealed 195 drug targets and 1608 disease targets,with 76 common drug-disease targets,including signal transducer and activator of transcription 3(STAT3),proto-oncogene tyrosine-protein kinase Src(SRC),matrix metalloproteinase-9(MMP9),Caspase 3,and toll-like receptor 4(TLR4)as key targets.Gene Ontology analysis identified 325 biological processes,48 cellular components,and 72 molecular functions,while Kyoto Encyclopedia of Genes and Genomes analysis identified 113 pathways.Molecular docking demonstrated strong binding affinities between active compounds and their targets.In the animal study,SZF treatment alleviated pathological damage and improved serum and urine biochemical markers compared to the Model group(P<0.05,P<0.01,P<0.001).Western blot analysis showed a significant reduction in phosphorylated-STAT3,phosphorylatedSRC,MMP9,TLR4,and Caspase3 expression in renal tissues of SZF-treated mice(P<0.001).CONCLUSION:SZF may exert therapeutic effects on UAN through multiple targets and pathways.
基金supported by the Qi-Huang Chief Scientist Program of the National Administration of Traditional Chinese Medicine(2020)the National Key Research and Development Program of China(No.2022YFC3501705)+1 种基金Shanghai Sailing Program(No.23YF1447500)the China Postdoctoral Science Foundation(No.2023M732335).
文摘Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.
基金jointly supported by the National Natural Science Foundation of China(No.22320102005,22036007)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0750200)+1 种基金the Provincial Key Laboratory Innovation Research Center Construction Project(ZCX202401)the Zhejiang Provincial Research Institute Support Fund Project in 2025。
文摘The escalating diversity of per-and polyfluoroalkyl substances(PFAS),arising from both intentional synthesis and inadvertent generation and release,has led to increasingly complex environmental PFAS compositions.In recent years,unknown PFAS have been frequently identified in the environment.However,the structural diversity and lack of corresponding reference standards pose significant challenges for the detection and identification of PFAS.Traditional targeted screening methods are often inadequate for detecting these compounds,making nontargeted analysis(NTA)using high-resolution mass spectrometry(HRMS)essential for identifying unknown or suspected contaminants.Nevertheless,existing NTA techniques still face limitations in comprehensively characterizing the full spectrum of PFAS in the environment.Continuous optimization and development of sample preparation methods,instrumental analytical techniques,data processing algorithms,and software are gradually expanding the coverage of NTA for diverse PFAS.This review summarizes recent advances in HRMS-based NTA methodologies for PFAS,encompassing sample preparation,separation techniques,HRMS instrument and data acquisition modes,PFAS screening strategies,and NTA data processing approaches.Furthermore,the review discusses the current challenges and prospects of PFAS NTA,such as an in-depth exploration of gas chromatography-HRMS(GC-HRMS)applications in NTA,and the utilization of machine learning(ML)models for efficient processing of complex NTA datasets.Addressing these challenges will significantly enhance the accuracy and efficiency of PFAS identification in the environment,providing a scientific basis for the regulation and control of PFAS in the future.
基金Supported by the Projects of Design and Statistics of Clinical Trials in Traditional Chinese Medicine,No.A YXC2022-01-0110Exploring the Mechanism by which Pingyang Yuyin Granules Improve Hypertensive Kidney Injury Based on the'Balance'Theory of PPARγ/HGF and TGF-β1/Smads Signaling Pathways,No.Y2022ZR09.
文摘BACKGROUND Hypertension is a significant global health concern and serves as a critical risk factor for cardiovascular diseases,stroke,and renal failure.Traditional Chinese Medicine(TCM)has been utilized for an extended period to address hypertension,with the syndrome known as Yin deficiency and Yang hyperactivity syndrome(YDYHS)frequently observed in individuals with elevated blood pressure.This syndrome is characterized by symptoms including dizziness,tinnitus,irritability,and insomnia,which are thought to result from an imbalance between Yin,representing the cooling and nourishing aspects,and Yang,denoting the active and warming aspects of the body.Despite the prevalent application of TCM in clinical settings,the metabolic mechanisms underlying the YDYHS in the context of hypertension remain inadequately elucidated.AIM To explore the differential plasma metabolites and associated pathways in hypertensive patients with YDYHS using gas chromatography-mass spectrometry(GC-MS)to elucidate the distinctive blood metabolite pattern in this patient population.METHODS GC-MS was used to analyze plasma samples from 51 hypertensive patients with YDYHS and 20 healthy controls.Chemometric methods,including principal component analysis and partial least squares discriminant analysis,were employed to identify potential biochemical patterns.Simultaneously,the high-quality Kyoto Encyclopedia of Genes and Genomes metabolic pathways database was used to identify associated metabolic pathways.Using variable importance in projection and receiver operating characteristic curve analyses,potential biomarkers were extracted to assess their clinical utility.RESULTS Metabolomic profiling of hypertensive patients with YDYHS identified 20 potential biomarkers(4-hydroxybenzoic acid,pectin,1,2,3-trihydroxybenzene,D-ribose,3-hydroxybutyric acid,quinic acid,L-lysine,oleic acid,2-hydroxybutyric acid,linoleic acid,citric acid,alpha-tocopherol,D-glucuronic acid,glycerol,N-acetyl-L-aspartic acid,betamannosylglycerate,indolelactic acid,L-glutamic acid,D-maltose,L-aspartic acid)and four metabolic pathways(linoleic acid metabolism;alanine,aspartate and glutamate metabolism;D-glutamine and D-glutamate metabolism;arginine biosynthesis).The identified differential metabolites may serve as potential biomarkers for distinguishing hypertensive patients with YDYHS from healthy controls.The area under the curve values ranged from 0.750 to 0.866.Receiver operating characteristic curve analysis showed that these differential metabolites can effectively classify hypertensive patients with YDYHS and healthy individuals.CONCLUSION The metabolomic analysis revealed a distinct blood metabolite pattern in hypertensive patients with YDYHS compared to the healthy control group,highlighting the potential role of the identified 20 biomarkers and four metabolic pathways in these patients.These findings may serve as an important material basis for understanding the occurrence and development of the disease,providing a scientific foundation for future clinical diagnosis.
