Substance Identification in Anti-Doping Control by Means of Mass Spectrometry. Data Reduction and Decision Criteria

A real doping case for which the national-level reviewing body deemed it probable that a misidentification of the national-level athlete’s sample occurred at the WADA accredited laboratory, thus making the athlete in this case strictly anonymous, is used to discuss criteria for data reduction and tolerance windows in GC-MS and LC-MS/MS. Stricter criteria for data reduction would remedy the present ambiguities.

Stepped-up development of accelerator mass spectrometry method for the detection of ^(60)Fe with the HI-13 tandem accelerator

The Moon provides a unique environment for investigating nearby astrophysical events such as supernovae.Lunar samples retain valuable information from these events,via detectable long-lived“fingerprint”radionuclides such as^(60)Fe.In this work,we stepped up the development of an accelerator mass spectrometry(AMS)method for detecting^(60)Fe using the HI-13tandem accelerator at the China Institute of Atomic Energy(CIAE).Since interferences could not be sufficiently removed solely with the existing magnetic systems of the tandem accelerator and the following Q3D magnetic spectrograph,a Wien filter with a maximum voltage of±60 kV and a maximum magnetic field of 0.3 T was installed after the accelerator magnetic systems to lower the detection background for the low abundance nuclide^(60)Fe.A 1μm thick Si_(3)N_(4) foil was installed in front of the Q3D as an energy degrader.For particle detection,a multi-anode gas ionization chamber was mounted at the center of the focal plane of the spectrograph.Finally,an^(60)Fe sample with an abundance of 1.125×10^(-10)was used to test the new AMS system.These results indicate that^(60)Fe can be clearly distinguished from the isobar^(60)Ni.The sensitivity was assessed to be better than 4.3×10^(-14)based on blank sample measurements lasting 5.8 h,and the sensitivity could,in principle,be expected to be approximately 2.5×10^(-15)when the data were accumulated for 100 h,which is feasible for future lunar sample measurements because the main contaminants were sufficiently separated.

Ultra-soft Desorption Assisted Mass Spectrometry using Picosecond Infrared Laser for the Detection of lons in the Liquid Surface

To identify the species in liquid surface using mass spectrometry,we must eliminate or reduce interferences during the vaporization or desorption of the species from the liquid surface.It is much more challenging to isolate the ionic,larger species from the liquid surface,because of the frangible structures and the higher solvation energies of those species.Here we demonstrate a new mass spectrometry in which the ionic species at the liquid surface can be desorbed with ultrasoft infrared picosecond laser pulses while the liquid surface is not breached.This laser desorption assisted mass spectrometry is not only a powerful tool to detect the fragile species but also promising to investigate vibrational energy transfer dynamics in the liquid surface.

Dual mass spectrometry imaging and spatial metabolomics to investigate the metabolism and nephrotoxicity of nitidine chloride

Evaluating toxicity and decoding the underlying mechanisms of active compounds are crucial for drug development.In this study,we present an innovative,integrated approach that combines air flowassisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI),time-of-flight secondary ion mass spectrometry(ToF-SIMS),and spatial metabolomics to comprehensively investigate the nephrotoxicity and underlying mechanisms of nitidine chloride(NC),a promising anti-tumor drug candidate.Our quantitive AFADESI-MSI analysis unveiled the region specific of accumulation of NC in the kidney,particularly within the inner cortex(IC)region,following single and repeated dose of NC.High spatial resolution ToF-SIMS analysis further allowed us to precisely map the localization of NC within the renal tubule.Employing spatial metabolomics based on AFADESI-MSI,we identified over 70 discriminating endogenous metabolites associated with chronic NC exposure.These findings suggest the renal tubule as the primary target of NC toxicity and implicate renal transporters(organic cation transporters,multidrug and toxin extrusion,and organic cation transporter 2(OCT2)),metabolic enzymes(protein arginine N-methyltransferase(PRMT)and nitric oxide synthase),mitochondria,oxidative stress,and inflammation in NC-induced nephrotoxicity.This study offers novel insights into NC-induced renal damage,representing a crucial step towards devising strategies to mitigate renal damage caused by this compound.

Improved isochronous mass spectrometry with tune measurement

In conventional isochronous mass spectrometry(IMS)performed on a storage ring,the precision of mass measurements for short-lived nuclei depends on the accurate determination of the revolution times(T)of stored ions.However,the resolution of T inevitably deteriorates due to the magnetic rigidity spread of the ions,limiting the mass-resolving power.In this study,we used the betatron tunes Q(the number of betatron oscillations per revolution)of the ions and established a correlation between T and Q.From this correlation,T was transformed to correspond to a fixed Q with higher resolution.Using these transformed T values,the masses of ^(63)Ge,^(65)As,^(67)Se,and ^(71)Kr agreed well with the mass values measured using the newly developed IMS(Bρ-IMS).We also studied the systematics of Coulomb displacement energies(CDEs)and found that anomalous staggering in CDEs was eliminated using new mass values.This method of T transformation is highly effective for conventional IMS equipped with a single time-of-flight detector.

Mass Spectrometry-based Deep Coverage Proteome:Evaluation of Cellular Protein Extraction Methods

The current study comprehensively evaluates four different protein extraction methods based on urea,sodium dodecyl sulfate(SDS),anionic surfactants(BT),and total RNA extractor(Trizol),aiming to optimize the sample preparation workflow for mass spectrometry-based proteomics.Using HeLa cells as an example,we found that the method employing the mass spectrometry-compatible surfactant BT reagent significantly reduces the total time consumed for protein extraction and minimizes protein losses during the sample preparation process.Further integrating the four protein extraction methods,we identified over 7000 proteins from HeLa cells without relying on pre-fractionation techniques,and 2990 of them were quantified using label-free quantification.It is worth noting that the BT and SDS methods demonstrate higher efficiency in extracting membrane proteins,while the Urea and Trizol methods are more effective in extracting proteins from nuclear and cytoplasmic fractions.In summary,this study provides a novel solution for deep proteome coverage,particularly in the context of cellular protein extraction,by integrating mass spectrometry-compatible surfactants with traditional extraction methods to effectively enhance protein identification numbers.

Bacterial Protein Profiling——Comparison of Three Mass Spectrometry Methodologies

Profiling the protein composition of bacteria is essential for understanding their biology,physiology and interaction with environment.Mass spectrometry has become a pivotal tool for protein analysis,facilitating the examination of expression levels,molecular masses and structural modifications.In this study,we compared the performance of three widely-used mass spectrometry methods,i.e.,matrix-assisted laser desorption/ionization(MALDI)protein fingerprinting,top-down proteomics and bottom-up proteomics,in the profiling of bacterial protein composition.It was revealed that bottom-up proteomics provided the highest protein coverage and exhibited the greatest protein profile overlap between bacterial species.In contrast,MALDI protein fingerprinting demonstrated superior detection reproducibility and effectiveness in distinguishing between bacterial species.Although top-down proteomics identified fewer proteins than bottom-up approach,it complemented MALDI fingerprinting in the discovery of bacterial protein markers,both favoring abundant,stable,and hydrophilic bacterial ribosomal proteins.This study represents the most systematic and comprehensive comparison of mass spectrometry-based protein profiling methodologies to date.It provides valuable guidelines for the selection of appropriate profiling strategies for specific analytical purposes.This will facilitate studies across various fields,including infection diagnosis,antimicrobial resistance detection and pharmaceutical target discovery.

Determination of Ten Kinds of Alpha-2 Agonists Residues in Animal Derived Food by UHPLC-Triple Quadrupole/Composite Linear Ion Trap Mass Spectrometry

[Objectives]The paper was to establish an ultra high performance liquid chromatography-quadrupole/linear ion trap complex mass spectrometry for the determination of 10 kinds ofα2-receptor agonists in animal derived food.[Methods]The samples were extracted with sodium carbonate buffer solution and ethyl acetate,and analyzed by mass spectrometry after solid phase extraction and high performance liquid chromatography separation.[Results]Ten kinds ofα2-receptor agonists showed a good linear relationship in the range of 1-100μg/mL,with the average recovery of over 69%and the relative standard deviation less than 8.32%.The detection limit of 10 kinds of α_(2)-receptor agonists was up to 1μg/kg.[Conclusions]The method has good selectivity and strong anti-interference ability,and can meet the requirements of 10 kinds ofα2-receptor agonists residues in animal derived food.

Research on the Upper Limit of Accuracy for Predicting Theoretical Tandem Mass Spectrometry

In recent years, numerous theoretical tandem mass spectrometry prediction methods have been proposed, yet a systematic study and evaluation of their theoretical accuracy limits have not been conducted. If the accuracy of current methods approaches this limit, further exploration of new prediction techniques may become redundant. Conversely, a need for more precise prediction methods or models may be indicated. In this study, we have experimentally analyzed the limits of accuracy at different numbers of ions and parameters using repeated spectral pairs and integrating various similarity metrics. Results show significant achievements in accuracy for backbone ion methods with room for improvement. In contrast, full-spectrum prediction methods exhibit greater potential relative to the theoretical accuracy limit. Additionally, findings highlight the significant impact of normalized collision energy and instrument type on prediction accuracy, underscoring the importance of considering these factors in future theoretical tandem mass spectrometry predictions.

Βρ-defned isochronous mass spectrometry at the storage ring CSRe

A novel technique of isochronous mass spectrometry(IMS),termed Bρ-defned IMS,was developed at the experimental cooler-storage ring CSRe in Lanzhou for the frst time.Two time-of-fight detectors were installed in a straight section of the CSRe,thereby enabling simultaneous measurements of the velocity and revolution time of each stored short-lived ion.This technique boosts the broadband precision,efciency,sensitivity,and accuracy of mass measurements of short-lived exotic nuclides.Using Bρ-defned IMS,the masses of^(22)Al,^(62)Ge,^(64)As,^(66)Se,and^(70)Kr were measured for the frst time,and the masses of^(65)As,^(67)Se,and other 21 nuclides were redetermined with improved accuracy.Mass data have been used in studies of relevant issues regarding nuclear structures and nuclear astrophysics.Herein,we review the development of experimental techniques and main physical results and outline plans for future experiments.

Mapping conformational changes on bispecific antigen-binding biotherapeutic by covalent labeling and mass spectrometry

Biotherapeutic's higher order structure(HOS)is a critical determinant of its functional properties and conformational relevance.Here,we evaluated two covalent labeling methods:diethylpyrocarbonate(DEPC)-labeling and fast photooxidation of proteins(FPOP),in conjunction with mass spectrometry(MS),to investigate structural modifications for the new class of immuno-oncological therapy known as bispecific antigen-binding biotherapeutics(BABB).The evaluated techniques unveiled subtle structural changes occurring at the amino acid residue level within the antigen-binding domain under both native and thermal stress conditions,which cannot be detected by conventional biophysical techniques,e.g.,near-ultraviolet circular dichroism(NUV-CD).The determined variations in labeling uptake under native and stress conditions,corroborated by binding assays,shed light on the binding effect,and highlighted the potential of covalent-labeling methods to effectively monitor conformational changes that ultimately influence the product quality.Our study provides a foundation for implementing the developed techniques in elucidating the inherent structural characteristics of novel therapeutics and their conformational stability.

Determination of 14 Organophosphorus Pesticide Residues in Mutton by Gel Permeation Chromatography-Gas Chromatography-Mass Spectrometry(GPC-GC-MS)

[Objectives]This study was conducted to purify mutton samples by gel permeation chromatography(GPC).[Methods]Fourteen organophosphorus pesticide residues in samples were qualitatively and quantitatively analyzed by gas chromatography-mass spectrometry(GC-MS)in selective ion scanning mode(SIM).[Results]The organophosphorus pesticide standard solutions showed good linearity in the mass concentration range of 0.1-10.0μg/ml with correlation coefficients(r)not lower than 0.999,and the detection limits(S=3 N)ranged from 0.01 to 0.05 mg/kg.The average recovery values were in the range of 80.2%-99.7%,with relative standard deviations(RSDs,n=3)in the range of 1.8%-6.3%,at the addition levels of 0.5,1.0 and 2.0 mg/kg.[Conclusions]The method is simple,sensitive and accurate,and can be used for the determination of organophosphorus pesticide residues in mutton.

Chemical profiling of bioactive compounds in the methanolic extract of wild leaf and callus of Vitex negundo using gas chromatographymass spectrometry

BACKGROUND The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques for drug therapy.Vitex negundo(V.negundo),a perennial herb belonging to the Varbanaceae family,is extensively used in conventional medication.AIM To determine the existence of therapeutic components in leaf and callus extracts from wild V.negundo plants using gas chromatography-mass spectrometry(GCMS).METHODS In this study,we conducted GC-MS on wild plant leaf extracts and correlated the presence of constituents with those in callus extracts.Various growth regulators such as 6-benzylaminopurine(BAP),2,4-dichlorophenoxyacetic acid(2,4-D),α-naphthylacetic acid(NAA),and di-phenylurea(DPU)were added to plant leaves and in-vitro callus and grown on MS medium.RESULTS The results clearly indicated that the addition of BAP(2.0 mg/L),2,4-D(0.2 mg/mL),DPU(2.0 mg/L)and 2,4-D(0.2 mg/mL)in MS medium resulted in rapid callus development.The plant profile of Vitex extracts by GC-MS analysis showed that 24,10,and 14 bioactive constituents were detected in the methanolic extract of leaf,green callus and the methanolic extract of white loose callus,respectively.CONCLUSION Octadecadienoic acid,hexadecanoic acid and methyl ester were the major constituents in the leaf and callus methanolic extract.Octadecadienoic acid was the most common constituent in all samples.The maximum concentration of octadecadienoic acid in leaves,green callus and white loose callus was 21.93%,47.79%and 40.38%,respectively.These findings demonstrate that the concentration of octadecadienoic acid doubles in-vitro compared to in-vivo.In addition to octadecadienoic acid;butyric acid,benzene,1-methoxy-4-(1-propenyl),dospan,tridecanedialdehyde,methylcyclohexenylbutanol,chlorpyrifos,n-secondary terpene diester,anflunine and other important active compounds were also detected.All these components were only available in callus formed in-vitro.This study showed that the callus contained additional botanical characteristics compared with wild plants.Due to the presence of numerous bioactive compounds,the medical use of Vitex for various diseases has been accepted and the plant is considered an important source of therapeutics for research and development.

Anterior mediastinal masses and thymic cysts

Cystic lesions of the anterior mediastinum in children suggest a well-known group of benign lesions that are comparatively frequent.Thymic cysts(TCs)are mostly positioned in the anterior mediastinum and some patients in the neck.Benign TCs classified as congenital intra-thoracic mesothelial cysts are commonly asymptomatic and have slight clinical significance.Multilocular TC,which can mimic another anterior mediastinal cystic tumor and is seen in adults,is more clinically important.It is a sporadic mediastinal lesion thought to arise in the course of acquired inflammation.Congenital mediastinal cysts represent 3%-6%of all mediastinal tumors and 10%-18%of radiologically reported mediastinal masses.Mediastinal TCs are uncommon and it is hard to know their true incidence.About 60%of cases with mediastinal TCs are asymptomatic,and the remainder of patients complains of nonspecific symptoms(e.g.,chest pain,dyspnea,or cough).The literature suggests that most cysts are benign,but an indefinite percentage may have a neoplastic process and result in significant compressive symptoms over time.Clinical symptoms of TCs vary depending on the location.In addition,frequent symptoms at the appearance of enlarged benign thymic and mediastinal cysts generally contain compressive symptoms(e.g.,respiratory distress,thymic pain,and symptoms related to Horner syndrome,hoarseness,dysphonia,dyspnea,orthopnea,wheezing,and fever).Many TCs have cystic density and a neat border and are simple to diagnose with radiological imaging.However,some TCs are hard to identify before surgery and may be misidentified as thymomas depending on their site and computed tomography results.Excision by thoracotomy,median sternotomy,or video-assisted techniques is essential for conclusive diagnosis,management,and abolition of relapse of anterior mediastinal masses and TCs.Histopathologic examination may be required after surgery.Considering the extent of the mass and the preliminary inability to make a definitive diagnosis,en bloc excision of the cyst was thought to be preferred to circumvent likely complications(e.g.,perforation,spillage of the contents,or incomplete excision).

Optimizing distribution of multiple tuned mass dampers for building structures with inverse element exchange method

Multiple tuned mass dampers(MTMDs)reduce dynamic response with multiple specified frequencies of building structures.Many optimization algorithms for placement design exist,though they rarely conform to code-based verification nor produce high quality solutions without high computational effort and high complexity.This study proposes an inverse element exchange method(IEEM)with multi-level programming and compares it to a single tuned mass damper(STMD)and uniform distribution of multiple tuned mass dampers in the frequency and time domains.A ten-story shear building is used for the numerical case study.The results show that the proposed method can offer improvement over the STMD,uniform distribution of multiple tuned mass dampers,and distribution optimized by genetic algorithms(GA)with regard to minimizing the interstory drift ratio(IDR)in both the frequency and time domains and the time consumption for optimization.

Effect of surface crack on the bearing capacity of strip footing placed on rock mass

In hilly regions,the existence of surface cracks in rock mass induces a potential threat to structural stability.Thus,the present research aims to explore the impact of surface cracks on the loadbearing capacity of strip footing placed on the rock mass.By taking into account the various boundary constraints across the surface of crack edges,the study investigates the presence of two categories of surface cracks,namely(1)separated crack,and(2)fine crack.The lower bound limit analysis is employed in conjunction with the finite element method(LBFELA)to conduct the numerical analysis.In order to evaluate rock mass yielding,the power conic programming(PCP)method is utilized to implement the generalized Hoek-Brown(GHB)failure criterion.The stability of the strip footing is analyzed by determining the bearing capacity factor(Nσγ),which is presented in the form of design charts by varying the strength parameters of rock,including the Geological Strength Index(GSI),Hoek-Brown material parameter(mi),Disturbance factor(D),and Normalised Uniaxial Compressive Strength(σci/γB),whereγis the unit weight of rock mass,and B is the width of strip footing.The study also investigates the impact of cracks on strip footings,considering different positions of the crack(LC)and depths of the crack(DC).The results demonstrate that the influence of the fine crack is only noticeable until the LC/B ratio reaches 6.However,for the separated crack,its impact remains significant even when the LC/B ratio exceeds 16.The appearance of fine crack at the edge of the footing results in a decrease in the magnitude Nσγof up to 45%,indicating a substantial reduction in the stability of the footing.The failure patterns are presented and discussed in detail for various cases in this study to examine the effect of surface cracks on the strip footing and to address the extent of the plastic collapse.

Cross-sectional study of the association between triglyceride glucose-body mass index and obstructive sleep apnea risk

BACKGROUND The triglyceride glucose-body mass index(TyG-BMI)is a novel indicator of insulin resistance(IR).Obstructive sleep apnea(OSA)is a prevalent disorder characterized by recurrent complete or partial collapse of the pharyngeal airway during sleep;however,the relationship between these two conditions remains unexplored.We hypothesized that a higher TyG-BMI is associated with the occurrence of OSA.AIM To assess the association between TyG-BMI and OSA in adults in the United States.METHODS A cross-sectional study was conducted utilizing data from the National Health and Nutrition Examination Surveys spanning from 2005-2008 to 2015-2018.TyGBMI was calculated as Ln[triglyceride(mg/dL)×fasting blood glucose(mg/dL)/2]×BMI.Restricted cubic splines were used to analyze the risk of TyG-BMI and OSA occurrence.To identify potential nonlinear relationships,we combined Cox proportional hazard regression with smooth curve fitting.We also conducted sensitivity and subgroup analyses to verify the robustness of our findings.RESULTS We included 16794 participants in the final analysis.Multivariate regression analysis showed that participants with a higher TyG-BMI had a higher OSA incidence.After adjusting for all covariates,TyG-BMI was positively correlated with the prevalence of OSA(odds ratio:1.28;95%confidence interval:1.17,1.40;P<0.001);no significant nonlinear relationship was observed.Subgroup analysis showed no strong correlation between TyG-BMI and OSA in patients with diabetes.The correlation between TyG-BMI and OSA was influenced by age,sex,smoking status,marital status,hypertensive stratification,and obesity;these subgroups played a moderating role between TyGBMI and OSA.Even after adjusting for all covariates,there was a positive association between TYG-BMI and OSA prevalence.CONCLUSION A higher TyG-BMI index is linked to higher chances of developing OSA.As TyG-BMI is an indicator of IR,managing IR may help reduce the risk of OSA.

Association between body mass index and lumbar spine volumetric bone mineral density in diabetic and non-diabetic patients

BACKGROUND The association between body mass index(BMI)and bone mineral density(BMD)has shown inconsistent results,varying by sex and skeletal site.Despite normal or elevated bone mass,individuals with type 2 diabetes have an increased risk of hip and vertebral fractures.AIM To assess lumbar spine trabecular volumetric BMD(vBMD)across different BMI categories in individuals with and without diabetes.METHODS This cross-sectional study included 966 men over 50 years old and 1001 postmenopausal women from the Pinggu Metabolic Disease Study.The vBMD of lumbar vertebrae 2 through 4 was measured using quantitative computed tomography.Total adipose tissue,subcutaneous adipose tissue(SAT),visceral adipose tissue(VAT),and lumbar skeletal muscle area were also quantified.RESULTS In men with obesity(P=0.038)and overweight(P=0.032),vBMD was significantly higher in the diabetes group compared to non-diabetic men.After adjusting for age and sex,no significant saturation effect between BMI and BMD was found in participants with diabetes or in women without diabetes.However,a BMI threshold of 22.33 kg/m²indicated a saturation point for vBMD in nondiabetic men.Independent predictors of vBMD in men included age(r=-0.387,P<0.001),BMI(r=0.130,P=0.004),and VAT(r=-0.145,P=0.001).For women,significant predictors were age(r=-0.594,P<0.001),BMI(r=0.157,P=0.004),VAT(r=-0.112,P=0.001),and SAT(r=-0.068,P=0.035).CONCLUSION The relationship between BMI and trabecular vBMD differs in individuals with and without diabetes.Overweight and obese men with diabetes exhibit higher vBMD.

Determination on Heavy Metals Content of Achyranthes bidentata Blume. through Inductively Coupled Plasma Mass Spectrometry (ICP-MS)

[Objective] The inductively coupled plasma mass spectrometry(ICP-MS)was constructed to determine the contents of lead,cadmium,mercury and arsenic in Archyranthes bidentata Blume.[Method]Under the optimum operation condition of ICP-MS,the samples were digested by microwave.The element 114In was taken as an internal standard element to compensate body effect and ICP-MS method was used to determine the contents of lead,cadmium,mercury and arsenic.[Result]For the determined elements,the correlation coefficient(r)of standard curve was over 0.9995 and recovery rate was from 96.7% to 106.4% while RSD was less than 11.2%.The result of determination showed that the heavy metal content in Archyranthes bidentata Blume.beyond standard was serious.[Conclusion]The constructed ICP-MS method with simple operation,rapid response,accuracy and high sensitivity in this experiment could be used for quality control of Chinese medicinal materials by detecting heavy metal contents in different Chinese medicinal materials from original places.

Study on Methanol Oxidation at Pt and PtRu Electrodes by Combining in situ Infrared Spectroscopy and Differential Electrochemical Mass Spectrometry

Methanol oxidation reaction （MOR） at Pt and Pt electrode surface deposited with various amounts of Ru （denoted as PtxRuy, nominal coverage y is 0.17, 0.27, and 0.44 ML） in 0.1 mol/L HClO4＋0.5 mol/L MeOH has been studied under potentiostatic conditions by in situ FTIR spectroscopy in attenuated-total-reflection con guration and di erential electro-chemical mass spectrometry under controlled flow conditions. Results reveal that （i） CO is the only methanol-related adsorbate observed by IR spectroscopy at all the Pt and PtRu electrodes examined at potentials from 0.3 V to 0.6 V （vs. RHE）; （ii） at Pt0.56Ru0.44, two IR bands, one from CO adsorbed at Ru islands and the other from COL at Pt substrate are detected, while at other electrodes, only a single band for COL adsorbed at Pt is observed; （iii） MOR activity decreases in the order of Pt0.73Ru0.27〉Pt0.56Ru0.44〉Pt0.83Ru0.17〉Pt; （iv） at 0.5 V, MOR at Pt0.73Ru0.27 reaches a current e ciency of 50% for CO2 production, the turn-over frequency from CH3OH to CO2 is ca. 0.1 molecule/（site sec）. Suggestions for further improving of PtRu catalysts for MOR are provided.