In this study, a new technique was developed using rapid ultra-performance liquid chromatography (UPLC)-based separation coupled with electrochemical detection by a boron-doped diamond (BDD) electrode for the detectio...In this study, a new technique was developed using rapid ultra-performance liquid chromatography (UPLC)-based separation coupled with electrochemical detection by a boron-doped diamond (BDD) electrode for the detection and quantification of three commonly used parabens (methylparaben (MP), ethylparaben (EP) and propylparaben (PP)). We aimed to reduce the analysis time by using UPLC coupled with a short reverse phase C 18 monolithic column (25 mm×4.6 mm). Operating the monolithic column at low back-pressure resulted in high flow rates. A mobile phaseconsisting of a 25:75 (v/v) ratio of acetonitrile:0.05 Mphosphate buffer (pH 5) at a flow rate of 2.5 mL·min?1 was used to perform the separation. The amperometric detection with the BDD electrode was found to be optimal and reliably reproducible at a detection potential of 1.5 V vs. Ag/AgCl. Under these conditions, the separation of the three targetanalytes (MP, EP and PP) was achieved in 2 min and was linear within a sample concentration range of 0.1 to 50.0 mg·L?1 (r2 values of 0.9970, 0.9994 and 0.9994 for MP, EP and PP, respectively). This method was successfully applied to determine the concentrations of each parabeninsix real samples with therecoveries ranging from of 80.3% - 98.9% for all three parabensfrom samples spiked at 12, 22 and 32 mg·L?1. Therefore, the proposed method can be used as an alternative rapid and selective method for the determination of paraben levels in real samples.展开更多
A highly sensitive, selective, and precise ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for simultaneous quantification of itraconazole and hydroxy itraconazole i...A highly sensitive, selective, and precise ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for simultaneous quantification of itraconazole and hydroxy itraconazole in human plasma by a single liquid-liquid extraction step. The precursor to product ion transitions of m/z 705.3/392.3, m/z 721.2/408.3 and m/z 708.2/435.4 were used to detect and quantify itraconazole, hydroxy itraconazole and itraconazole-d3 respectively. The lower limit of quantitation was found to be 0.500 ng/mL for itraconazole and 1.00 ng/mL for hydroxy itraconazole. The mean recoveries for itraconazole and hydroxy itraconazole were found to be 100.045% and 100.021%, respectively. This developed method with a chromatographic run time of 2.0 min was successfully applied to a bioequivalence study of 100 mg itraconazole capsule.展开更多
A method was developed for the detection of seven microcystins(microcystin-LR, RR, YR, LA, LY, LW and LF) in surface water using automatic solid-phase extraction(A-SPE) coupled with ultra-performance liquid chromatogr...A method was developed for the detection of seven microcystins(microcystin-LR, RR, YR, LA, LY, LW and LF) in surface water using automatic solid-phase extraction(A-SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS). The automated solid-phase extraction system was used to extract microcystins(MCs) from water samples. UPLC-MS/MS was used to determine MCs concentrations in just 5 min. Method detection limits were from 0.3 to 0.9 ng/L, microcystin recoveries ranged from 83.8% to 114%, and the relative standard deviation(RSD) varied from 5.6% to 12.5%. This analytical approach was found to be simple, highly sensitive, accurate, which required little manual operation. Additionally, to validate this analytical method, A-SPE+UPLC-MS/MS was applied to characterize the concentration of MCs in Taihu Lake, Wuxi, China.展开更多
Centrifugal ultrafiltration after methanol extraction of whole plasma was used as an optimal condition for the preparation of blood plasma before metabonomic studies. The plasma samples from 102 lung cancer patients a...Centrifugal ultrafiltration after methanol extraction of whole plasma was used as an optimal condition for the preparation of blood plasma before metabonomic studies. The plasma samples from 102 lung cancer patients and 34 healthy volunteers were prepared with this approach. With ultra-performance liquid chromatography（UPLC） coupled with quadrupole time-of-flight mass spectrometry（Q-TOF MS） analysis, the samples were investigated in order to find potential disease biomarkers. After data acquisition, orthogonal signal correction partial least squares models were built to differentiate the healthy volunteers from lung cancer patients and to identify metabolites that showed significantly different expression between the two groups. Several metabolite ions were identified as potential biomarkers according to the variable importance in the project（VIP） value in both ion modes. Five lysophosphatidylcholines were further identified as specifically lysoPC 16：0, isomer of lysoPC 16：0, lysoPC 18：0, lysoPC 18：1 and lysoPC 18：2. These results suggest that UPLC coupled with Q-TOF MS is an effective technique for the analysis of plasma metabolites in metabonomic studies.展开更多
The residual clothianidin in rice was determined by Agilent ultra-performance liquid chromatography-tandem mass spectrometry, quantified by external standard method, adjusted the elution gradient of mobile phase and t...The residual clothianidin in rice was determined by Agilent ultra-performance liquid chromatography-tandem mass spectrometry, quantified by external standard method, adjusted the elution gradient of mobile phase and the parameters of ion monitoring and analysis, and compared the precision of recovery and repeatability of parallel standard addition. The experimental results showed that the clothianidin residue in rice was ultrasonically extracted by 0.1% acetic acid-acetonitrile and purified by matrix dispersed solid-phase extractant, and the linearity of the test was good. The correlation coefficient R was greater than or equal to 0.999, and the quantitative limit was 0.010mg/kg. The recoveries of clothianidin residue were 96.9% and 95.0% respectively, and the repeatability precision RSD was 1.48%. In this paper, the recovery and precision of parallel standard addition for determination of clothianidin residues in rice by Agilent ultra-performance liquid chromatography-tandem mass spectrometry were studied. Good results were obtained, which could provide reference for the detection of pesticide residues in other cereals.展开更多
N-nitrosodimethylamine （NDMA） and several other N-nitrosamines have been detected as disinfection by-products in drinking waters in many countries around the world. An ultra-performance liquid chromatography- tandem...N-nitrosodimethylamine （NDMA） and several other N-nitrosamines have been detected as disinfection by-products in drinking waters in many countries around the world. An ultra-performance liquid chromatography- tandem mass spectrometry method with solid phase extraction sample preparation was developed to study the occurrence of N-nitrosamines in several water treatment plants and distribution systems in China. Isotope labeled N-nitrosodi-n-propylamine-dl4 （NDPA-dl4） was selected as the internal standard for quantification. The solid phase extraction procedures including pH, enrichment process and MS/MS parameters including capillary voltage, cone gas flow, cone voltage, collision energy were optimized to give average recoveries of 26% to 112% for nine N- nitrosamine species. The instrument detection limits were estimated to range from 0.5 to 5μg.L-1 for the nine N- nitrosamine species. NDMA and several other N-nitrosa- mines were found at fairly high concentrations in several water treatment plants and distribution systems. NDMA was found in all locations, and the highest concentrations in cities B, G, T, and W were 3.0, 35.7, 21.3, and 19.7 ng. L 1, respectively. A wide range of N-nitrosamines concentrations and species were observed in different locations. Higher concentrations of N-nitrosamines were detected in distribution systems that were further away from the treatment plants, suggesting that the contact time between the residual disinfectant and natural organic matter may play an important role in the formation of these compounds.展开更多
Background：Tuberculosis （TB） is a chronic wasting inflammatory disease characterized by multisystem involvement,which can cause metabolic derangements in afflicted patients.Metabolic signatures have been exploited ...Background：Tuberculosis （TB） is a chronic wasting inflammatory disease characterized by multisystem involvement,which can cause metabolic derangements in afflicted patients.Metabolic signatures have been exploited in the study of several diseases.However,the serum that is successfully used in TB diagnosis on the basis of metabolic profiling is not by much.Methods：Orthogonal partial least-squares discriminant analysis was capable of distinguishing TB patients from both healthy subjects and patients with conditions other than TB.Therefore,TB-specific metabolic profiling was established.Clusters of potential biomarkers for differentiating TB active from non-TB diseases were identified using Mann-Whitney U-test.Multiple logistic regression analysis of metabolites was calculated to determine the suitable biomarker group that allows the efficient differentiation of patients with TB active from the control subjects.Results：From among 271 participants,12 metabolites were found to contribute to the distinction between the TB active group and the control groups.These metabolites were mainly involved in the metabolic pathways of the following three biomolecules：Fatty acids,amino acids,and lipids.The receiver operating characteristic curves of3D,7D,and 11D-phytanic acid,behenic acid,and threoninyl-γ-glutamate exhibited excellent efficiency with area under the curve （AUC） values of 0.904 （95% confidence interval [CI]：0.863-0.944）,0.93 （95% CI：0.893-0.966）,and 0.964 （95% CI：0.941-0.988）,respectively.The largest and smallest resulting AUCs were 0.964 and 0.720,indicating that these biomarkers may be involved in the disease mechanisms.The combination of lysophosphatidylcholine （18∶0）,behenic acid,threoninyl-γ-glutamate,and presqualene diphosphate was used to represent the most suitable biomarker group for the differentiation of patients with TB active from the control subjects,with an AUC value of 0.991.Conclusion：The metabolic analysis results identified new serum biomarkers that can distinguish TB from non-TB diseases.The metabolomics-based analysis provides specific insights into the biology of TB and may offer new avenues for TB diagnosis.展开更多
Objective:To study the differences between the serum metabolites in patients with adenomatous polyps of the colon and yang-deficiency constitution and those without colon polyps and with balanced constitution,and look...Objective:To study the differences between the serum metabolites in patients with adenomatous polyps of the colon and yang-deficiency constitution and those without colon polyps and with balanced constitution,and look for biomarkers that can be used to distinguish between the two groups.Methods:General patient information was gathered,and Chinese medicine constitutions were collected in 940 patients who underwent electronic colonoscopy.A total of 119 patients with adenomatous polyps of the colon and yang-deficiency constitution were included in the experimental group,and 150 patients without colon polyps and with balanced constitution were included in the control group.Metabolomics analysis was performed on the fasting venous blood obtained from each patient in both groups.Principal component analysis and orthogonal partial least squares discriminant analysis were performed on the detection results,potential biomarkers were screened,metabolic pathway changes were determined,and the metabolic processes involved were discussed.Results:A total of 59 differential biomarkers between the experimental group and the control group were identified.The differential metabolites were found mainly in the glycerophospholipid metabolism pathway,and the bile acid 3-oxo-4,6-choladienoic acid was the biomarker that distinguished the experimental group from the control group.Conclusions:With the help of metabolomics analysis,the differential metabolites in patients with adenomatous polyps of the colon and yang-deficiency constitution and those in patients without colon polyps and with balanced constitution could be identified.The biomarker 3-oxo-4,6-choladienoic acid may have potential diagnostic value in patients with adenomatous polyp of the colon and yang-deficiency constitution.(Trial Registration No.NCT02986308)展开更多
Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline ...Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice;during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix Win Nonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in C_(max) of ferulic acid and formononetin, AUC_(all) of caffeic acid and ferulic acid, and AUC_(INF_obs) of ferulic acid. Conversely, an increase in the Vz_F_obs and MRT_(last) of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.展开更多
Objective:There are different geographic origins of Aconiti Kusnezoffii Radixs(AKRs)sold in the market with different quality.This study aims to establish a rapid analysis method to distinguish the different geographi...Objective:There are different geographic origins of Aconiti Kusnezoffii Radixs(AKRs)sold in the market with different quality.This study aims to establish a rapid analysis method to distinguish the different geographic origins of AKRs and to realize the rapid evaluation of their quality.Methods:An ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry(UPLC-Q-TOF MS)method was utilized to acquire the constituents'information of AKRs from different geographic origins.MSE data and Progenesis QI software were employed to identify the chemical constitutes.Principal component analysis(PCA)was applied to comparing MS data to find the chemical markers of AKRs from different geographic origins.Results:Twenty-three components were detected and 17 out of them were identified,including diester-diterpenoid alkaloids,monoester-diterpenoid alkaloids,and amine-diterpenoid alkaloids.Three pairs of isomers were detected and two of them were distinguished by the retention time of standard samples.Thirteen chemical markers were screened out through PCA and orthogonal partial least square discriminant analysis.Through detecting Napelline or isomer of Napelline(m/z 360.2530)and Aconifine(m/z 662.3170),AKRs from inner Mongolia autonomous could be screened.According to the existence of benzoylaconine(m/z 604.3108)and Indaconitine(m/z 630.3159),it could be confirmed that the AKRs are from Xinjiang Uygur autonomous.AKRs that cannot detect compounds above-mentioned could be from Liaoning or Shanxi Province.Conclusions:The chemical profile could be used not only to distinguish the AKRs from different geographic origins but also to identify the true and false of AKRs.This study lays a foundation for the study of efficacy and toxic of AKRs.展开更多
A rapid and high selective ultra-performance liquid chromatography(UPLC)with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin,paeoniflorin,picroside I,picroside II,s...A rapid and high selective ultra-performance liquid chromatography(UPLC)with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin,paeoniflorin,picroside I,picroside II,saikosaponin A,and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard.One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples.Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column(100 mm×2.1 mm,1.7μm)at a flow rate of 0.4 m L/min,using gradient mode containing 0.1%formic acid in water and acetonitrile were used as the Mobile phase A and B.Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components.Calibration curves showed good linearity(R^2>0.9908)over a wide concentration range for all compounds.The intra-and interday precision(relative standard deviation)ranged 2.4%–7.0%and 2.6%–8.0%,respectively.The accuracy(relative error)was from-13.0%to 13.2%at all quality control levels.The recovery ranged from 81.1%to 92.5%.The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan-Shu Yu-Fang.The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.展开更多
Background: Curcuma wenyujin rhizome(CWR) is a commonly used Chinese herbal medicine for treating blood stasis in China for 1000 of years. However, the underlying mechanism of CWR remains unclear. Aims and Objectives:...Background: Curcuma wenyujin rhizome(CWR) is a commonly used Chinese herbal medicine for treating blood stasis in China for 1000 of years. However, the underlying mechanism of CWR remains unclear. Aims and Objectives: The purpose of this study is to clarify the bioactive mechanism of CWR in treating blood stasis. Materials and Methods: In this study, pharmacological indexes, including hemorheology and four blood coagulation indexes were tested. Bile and urine metabolomics were engaged by UPLC-Q/TOF-MS. Multivariate statistical analysis were used to screen out differential endogenous metabolites. Results: The results indicated that CWR significantly ameliorated the hemorheology and coagulation functions of acute blood stasis(ABS) model rats. Moreover, 27 endogenous metabolites between the CWR group and the ABS group were screened, and the levels were all improved to certain degrees by CWR preadministration. Metabonomics results indicated that ABS was mainly related to linoleic acid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism, pentose and glucuronate intercereasonversions, steroid hormone biosynthesis, and primary bile acid biosynthesis. Conclusion: In a word, the metabolomics method is consistent with the holistic view of traditional Chinese medicine(TCM) that can be a powerful means to illustrate the biological activity mechanism of CWR in treating blood stasis and to offer research demonstration for further study on the effector mechanism of TCM.展开更多
Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Na...Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.展开更多
OBJECTIVE:To examine Hedan tablet(HDT,荷丹片)'s potential mechanisms in hyperlipidemic rats induced by a high-fat diet(HFD),as well as its regulatory effects and primary active constituents.METHODS:By using ultra-...OBJECTIVE:To examine Hedan tablet(HDT,荷丹片)'s potential mechanisms in hyperlipidemic rats induced by a high-fat diet(HFD),as well as its regulatory effects and primary active constituents.METHODS:By using ultra-performance liquid chromatography(UPLC)-quadrupole-time-of-flight(QTOF)-tandem mass spectrometry(MS/MS),the components of HDT that can enter the circulatory system were found,aiming to investigate its active constituents with pharmacological effects.Based on network pharmacology approaches,the relevant HDT targets in the therapy of hyperlipidemia were anticipated.The possible mechanism of HDT for hyperlipidemia treatment was verified by in-vivo experiments,and the main active components of HDT for hyperlipidemia treatment were analyzed via in-vitro experiments.RESULTS:UPLC-QTOF-MS/MS identified 30 components of HDT entering the circulatory system,primarily consisting of flavonoids,diterpenoids and alkaloids.The results of a network pharmacology study revealed that 30 active components mostly target 74 genes associated with hyperlipidemia.The primary active ingredients may include quercetin,kaempferol,and epicatechin,and the main gene targets may be tumor necrosis factor(TNF),interleukin-6(IL-6),interleukin 1 beta(IL-1β),etc.The results of animal experiments demonstrated that HDT can significantly regulate the blood lipid level in rats with HFD,improve the degree of inflammatory infiltration in rat liver cells,lower TNF-α,Creactive protein(CRP),IL-6,matrix metalloproteinase 9(MMP9) and malondialdehyde(MDA) levels while raising total superoxide dismutase(T-SOD) level.Meanwhile,HDT can considerably lower the expression of sterol regulatory element-binding transcription factor 2(SREBF2),3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR),and MMP9 while significantly increasing the expression of peroxisome proliferator-activated receptor alpha(PPAR-α) and PPAR-γ.In vitro study confirmed that quercetin and kaempferol could reduce the levels of IL-6,IL1B,MMP9 and HMGCR in the high-fat model of hepatoma G2 cells.CONCLUSIONS:The mechanism by which HDT treats hyperlipidemia involves modification of the lipid metabolism targets such as downregulating SREBF2,HMGCR and MMP9,and upregulating PPAR-α and PPAR-γ,as well as anti-inflammatory and antioxidant actions.This study provides a pharmacological and biological rationale for the use of HDT in clinical hyperlipidemia management.展开更多
XiaoShuanTongLuo （XSTL） is an important multi-herbal formula widely used as a traditional Chinese medicine （TCM）. In this paper, an ultra-performance liquid chromatography-electrospray ionization tandem mass spect...XiaoShuanTongLuo （XSTL） is an important multi-herbal formula widely used as a traditional Chinese medicine （TCM）. In this paper, an ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric method （UPLC-ESI-MS/MS） was developed for the simultaneous identification and quantification of 18 chemical constituents in the extract of XSTL. The analysis was performed in multiple-reaction monitoring （MRM） mode using positive and negative electrospray ionization （ESI）. A BEH C18 （2.1 mm× 100 mm, 1.7 μm） column with a gradient mobile phase of methanol-0.1% aqueous formic acid solution at a flow rate of 0.2 mL/min was used for separation. The standard curves of most components showed good linearity over the concentration range of 0.001-0.5 μg/mL with r = 0.9896-0.9996. The relative standard deviations （RSD） of intra-day and inter-day precision were all lower than 15% at low, middle, and high concentration levels. The RSD of stability analysis in 24 h were also lower than 15%. The validated method was employed to quantify 18 active components simultaneously in four different commercial brands of XSTL products in various dosage forms. The developed method was rapid, accurate, sensitive, and reproducible for the quality control of XSTL.展开更多
To establish a rapid and effective method for analysis and identification of the alkaloids from Ranunculus japoni- cus Thunb by ultra-performance liquid chromatogaraphy with quadruple-time-of-flight mass spectrometry ...To establish a rapid and effective method for analysis and identification of the alkaloids from Ranunculus japoni- cus Thunb by ultra-performance liquid chromatogaraphy with quadruple-time-of-flight mass spectrometry （UPLC/Q-TOF- MS） and discuss their fragmentation regularity, the UPLC/Q-TOF-MS was used to identify the alkaloids from Ranunculus japonicus Thunb by their MS data, tandem characteristic fragment ions and standards. In the end, 12 alkaloids were identi- fied from Ranunculus japonicus for the first time, and their fragmentation regularity was discussed. Thus, a rapid and effec- tive analysis and identification method for the alkaloids from Ranunculus japonicus by UPLC/Q-TOF-MS is established.展开更多
There exists an increasing need for precision measurement&pointing control and extreme motion stability for current and future space systems,e.g.,Ultra-Performance Spacecraft(UPS).Some notable technologies of real...There exists an increasing need for precision measurement&pointing control and extreme motion stability for current and future space systems,e.g.,Ultra-Performance Spacecraft(UPS).Some notable technologies of realizing Ultra-Pointing(UP)ability have been developed particularly for Ultra-accuracy Ultra-stability Ultra-agility(3 U)spacecraft over recent decades.Usually,Multilevel Compound Pointing Control Techniques(MCPCTs)are deployed in aerospace engineering,especially in astronomical observation satellites and Earth observation satellites.Modern controllers and/or algorithms,which are a key factor of MCPCTs for 3 U spacecraft,especially the jitter phenomena that commonly exist in a UPS Pointing Control System(PCS),have also been effectively used in some UP spacecraft for a number of years.Micro-vibration suppression approaches,however,are often proposed to deal with low-level mechanical vibration or disturbance in the microgravity environment that is common for UPS.This latter approach potentially is one of the most practical UP techniques for 3 U tasks.Some emerging advanced Disturbance-Free Payload(DFP)satellites that exploit the benefits of non-contact actuators have also been reported in the literature.This represents an interesting and highly promising approach for solving some challenging problems in the area.This paper serves as a state-of-the-art review of UP technologies and/or methods which have been developed,mainly over the last decade,specifically for or potentially could be used for 3 U spacecraft pointing control.The problems discussed in this paper are of reference significance to UPS and millisecond optical sensors,which are involved in Gaofeng Project,deep space exploration,manned space flight,and gravitational wave detection.展开更多
BACKGROUND Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver disease.Established non-invasive tests for monitoring fibrosis are lacking,and new bioma...BACKGROUND Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver disease.Established non-invasive tests for monitoring fibrosis are lacking,and new biomarkers of liver fibrosis and function are needed.AIM To depict the process of liver fibrosis and look for novel biomarkers for diagnosis and monitoring fibrosis progression.METHODS CCl4 was used to establish the rat liver fibrosis model.Liver fibrosis process was measured by liver chemical tests,liver histopathology,and Masson’s trichrome staining.The expression levels of two fibrotic markers includingα-smooth muscle actin and transforming growth factorβ1 were assessed using immunohistochemistry and real-time polymerase chain reaction.Dynamic changes in metabolic profiles and biomarker concentrations in rat serum during liver fibrosis progression were investigated using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.The discriminatory capability of potential biomarkers was evaluated by receiver operating characteristic(ROC)curve analysis.RESULTS To investigate the dynamic changes of metabolites during the process of liver fibrosis,sera from control and fibrosis model rats based on pathological results were analyzed at five different time points.We investigated the association of liver fibrosis with 21 metabolites including hydroxyethyl glycine,L-threonine,indoleacrylic acid,β-muricholic acid(β-MCA),cervonoyl ethanolamide(CEA),phosphatidylcholines,and lysophosphatidylcholines.Two metabolites,CEA andβ-MCA,differed significantly in the fibrosis model rats compared to controls(P<0.05)and showed prognostic value for fibrosis.ROC curve analyses performed to calculate the area under the curve(AUC)revealed that CEA andβ-MCA differed significantly in the fibrosis group compared to controls with AUC values exceeding 0.8,and can clearly differentiate early stage from late stage fibrosis or cirrhosis.CONCLUSION This study identified two novel biomarkers of fibrosis,CEA andβ-MCA,which were effective for diagnosing fibrosis in an animal model.展开更多
We investigated the antidepressant-like activity of Hemerocallis citrine Baroni extract(HCE)in a simulated microgravity(SMG)-induced rat model of depression using a metabolomics method.A rat model,generated via 14 d o...We investigated the antidepressant-like activity of Hemerocallis citrine Baroni extract(HCE)in a simulated microgravity(SMG)-induced rat model of depression using a metabolomics method.A rat model,generated via 14 d of SMG induction,was validated from the reduced sucrose preference and the enhanced immobility time in the forced swimming test.HCE and paroxetine reversed certain metabolite profiles.Anti-depressant effects of HCE might involve the regulation of several metabolic pathways,such as phenylalanine,glutamic acid,and tryptophan metabolism and changes in energy metabolism.5-Hydroxytryptophan,hippuric acid,phenylacetylglycine,citric acid,3-hydroxykynurenine,cyclic AMP,and L-DOPA profiles were altered upon HCE and paroxetine administration.Furthermore,glutamic acid was only regulated in the HCE group,while xanthurenic acid and deoxyuridine were reversed in the positive group,suggesting differences in the mechanisms between the positive drugs and HCE in improving glutamic acid metabolism.This study provided a theoretical foundation for the application of HCE in depression therapy.展开更多
Objective To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides(PSP)against kidney aging in D-galactose(D-gal)-induced aging mice,based on ultra-performance l...Objective To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides(PSP)against kidney aging in D-galactose(D-gal)-induced aging mice,based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive MS/MS).Methods A total of 36 C57 BL/6J mice were randomly allocated to six groups:control(CON),model(MOD),PSP low-dose(PSP-L),PSP medium-dose(PSP-M),PSP high-dose(PSP-H),and positive drug ascorbic acid(VC)groups.To create models of aging mice,D-gal was intraperitoneally administered to all other groups of mice except the CON group.After modeling,the appropriate Chinese medicine[PSP-L:150 mg/(kg·d),PSP-M:300 mg/(kg·d),PSP-H:600 mg/(kg·d)]or positive drug[ascorbic acid,300 mg/(kg·d)]was administered for intervention.Key markers of renal function in urine and serum of mice in each group,such as creatinine(Crea),urea nitrogen(BUN),and uric acid(UA)levels,as well as key indicators of oxidative stress in serum and kidney,including superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP.Hematoxylin and eosin(HE),periodic acid Schiff(PAS),andβ-galactosidase staining were used to assess the renal pathological changes.The metabolic profiles of serum,kidney,and urine samples from CON,MOD,and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS,and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites.Results Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators.Following the injection of PSP[PSP-H:600 mg/(kg·d)],the pathological indices associated with aging were adjusted to normal levels,renal function and oxidative stress were improved in aging mice,and renal pathological damage was markedly improved.Meanwhile,the potential biomarkers were identified by UPLCQ-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways,with P<0.05 as a threshold.The results showed that purine,sphingolipid,glycerophospholipid,tryptophan,and riboflavin metabolisms were the main metabolic pathways associated with aging.After administration of PSP,these pathological indices returned to normal levels,and biomarkers related to the aging process,such as adenosine monophosphate(AMP),tryptophan,and 5-hydroxytryptophan,also demonstrated,to some degree,reverse regulation(promoting synthesis).Conclusion Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice.PSP has been shown to protect against kidney aging by interfering with the purine,sphingolipid,glycerophospholipid,tryptophan,and riboflavin metabolisms in the kidney.展开更多
文摘In this study, a new technique was developed using rapid ultra-performance liquid chromatography (UPLC)-based separation coupled with electrochemical detection by a boron-doped diamond (BDD) electrode for the detection and quantification of three commonly used parabens (methylparaben (MP), ethylparaben (EP) and propylparaben (PP)). We aimed to reduce the analysis time by using UPLC coupled with a short reverse phase C 18 monolithic column (25 mm×4.6 mm). Operating the monolithic column at low back-pressure resulted in high flow rates. A mobile phaseconsisting of a 25:75 (v/v) ratio of acetonitrile:0.05 Mphosphate buffer (pH 5) at a flow rate of 2.5 mL·min?1 was used to perform the separation. The amperometric detection with the BDD electrode was found to be optimal and reliably reproducible at a detection potential of 1.5 V vs. Ag/AgCl. Under these conditions, the separation of the three targetanalytes (MP, EP and PP) was achieved in 2 min and was linear within a sample concentration range of 0.1 to 50.0 mg·L?1 (r2 values of 0.9970, 0.9994 and 0.9994 for MP, EP and PP, respectively). This method was successfully applied to determine the concentrations of each parabeninsix real samples with therecoveries ranging from of 80.3% - 98.9% for all three parabensfrom samples spiked at 12, 22 and 32 mg·L?1. Therefore, the proposed method can be used as an alternative rapid and selective method for the determination of paraben levels in real samples.
文摘A highly sensitive, selective, and precise ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for simultaneous quantification of itraconazole and hydroxy itraconazole in human plasma by a single liquid-liquid extraction step. The precursor to product ion transitions of m/z 705.3/392.3, m/z 721.2/408.3 and m/z 708.2/435.4 were used to detect and quantify itraconazole, hydroxy itraconazole and itraconazole-d3 respectively. The lower limit of quantitation was found to be 0.500 ng/mL for itraconazole and 1.00 ng/mL for hydroxy itraconazole. The mean recoveries for itraconazole and hydroxy itraconazole were found to be 100.045% and 100.021%, respectively. This developed method with a chromatographic run time of 2.0 min was successfully applied to a bioequivalence study of 100 mg itraconazole capsule.
基金Supported by the Environmental Monitoring and Research Foundation of Jiangsu Province(1621)the Taihu Lake Pollution Prevention and Control Project of Jiangsu Province(TH2016301)Postgraduate Research and Practice Innovation Program of Jiangsu Province in 2016(KYLX16_0813)
文摘A method was developed for the detection of seven microcystins(microcystin-LR, RR, YR, LA, LY, LW and LF) in surface water using automatic solid-phase extraction(A-SPE) coupled with ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS). The automated solid-phase extraction system was used to extract microcystins(MCs) from water samples. UPLC-MS/MS was used to determine MCs concentrations in just 5 min. Method detection limits were from 0.3 to 0.9 ng/L, microcystin recoveries ranged from 83.8% to 114%, and the relative standard deviation(RSD) varied from 5.6% to 12.5%. This analytical approach was found to be simple, highly sensitive, accurate, which required little manual operation. Additionally, to validate this analytical method, A-SPE+UPLC-MS/MS was applied to characterize the concentration of MCs in Taihu Lake, Wuxi, China.
基金Supported by the National Natural Science Foundation of China(No.30801513)the Knowledge Innovation Program of Chinese Academy of Sciences(No.KSCX2-YW-R-170)
文摘Centrifugal ultrafiltration after methanol extraction of whole plasma was used as an optimal condition for the preparation of blood plasma before metabonomic studies. The plasma samples from 102 lung cancer patients and 34 healthy volunteers were prepared with this approach. With ultra-performance liquid chromatography（UPLC） coupled with quadrupole time-of-flight mass spectrometry（Q-TOF MS） analysis, the samples were investigated in order to find potential disease biomarkers. After data acquisition, orthogonal signal correction partial least squares models were built to differentiate the healthy volunteers from lung cancer patients and to identify metabolites that showed significantly different expression between the two groups. Several metabolite ions were identified as potential biomarkers according to the variable importance in the project（VIP） value in both ion modes. Five lysophosphatidylcholines were further identified as specifically lysoPC 16：0, isomer of lysoPC 16：0, lysoPC 18：0, lysoPC 18：1 and lysoPC 18：2. These results suggest that UPLC coupled with Q-TOF MS is an effective technique for the analysis of plasma metabolites in metabonomic studies.
文摘The residual clothianidin in rice was determined by Agilent ultra-performance liquid chromatography-tandem mass spectrometry, quantified by external standard method, adjusted the elution gradient of mobile phase and the parameters of ion monitoring and analysis, and compared the precision of recovery and repeatability of parallel standard addition. The experimental results showed that the clothianidin residue in rice was ultrasonically extracted by 0.1% acetic acid-acetonitrile and purified by matrix dispersed solid-phase extractant, and the linearity of the test was good. The correlation coefficient R was greater than or equal to 0.999, and the quantitative limit was 0.010mg/kg. The recoveries of clothianidin residue were 96.9% and 95.0% respectively, and the repeatability precision RSD was 1.48%. In this paper, the recovery and precision of parallel standard addition for determination of clothianidin residues in rice by Agilent ultra-performance liquid chromatography-tandem mass spectrometry were studied. Good results were obtained, which could provide reference for the detection of pesticide residues in other cereals.
文摘N-nitrosodimethylamine （NDMA） and several other N-nitrosamines have been detected as disinfection by-products in drinking waters in many countries around the world. An ultra-performance liquid chromatography- tandem mass spectrometry method with solid phase extraction sample preparation was developed to study the occurrence of N-nitrosamines in several water treatment plants and distribution systems in China. Isotope labeled N-nitrosodi-n-propylamine-dl4 （NDPA-dl4） was selected as the internal standard for quantification. The solid phase extraction procedures including pH, enrichment process and MS/MS parameters including capillary voltage, cone gas flow, cone voltage, collision energy were optimized to give average recoveries of 26% to 112% for nine N- nitrosamine species. The instrument detection limits were estimated to range from 0.5 to 5μg.L-1 for the nine N- nitrosamine species. NDMA and several other N-nitrosa- mines were found at fairly high concentrations in several water treatment plants and distribution systems. NDMA was found in all locations, and the highest concentrations in cities B, G, T, and W were 3.0, 35.7, 21.3, and 19.7 ng. L 1, respectively. A wide range of N-nitrosamines concentrations and species were observed in different locations. Higher concentrations of N-nitrosamines were detected in distribution systems that were further away from the treatment plants, suggesting that the contact time between the residual disinfectant and natural organic matter may play an important role in the formation of these compounds.
文摘Background：Tuberculosis （TB） is a chronic wasting inflammatory disease characterized by multisystem involvement,which can cause metabolic derangements in afflicted patients.Metabolic signatures have been exploited in the study of several diseases.However,the serum that is successfully used in TB diagnosis on the basis of metabolic profiling is not by much.Methods：Orthogonal partial least-squares discriminant analysis was capable of distinguishing TB patients from both healthy subjects and patients with conditions other than TB.Therefore,TB-specific metabolic profiling was established.Clusters of potential biomarkers for differentiating TB active from non-TB diseases were identified using Mann-Whitney U-test.Multiple logistic regression analysis of metabolites was calculated to determine the suitable biomarker group that allows the efficient differentiation of patients with TB active from the control subjects.Results：From among 271 participants,12 metabolites were found to contribute to the distinction between the TB active group and the control groups.These metabolites were mainly involved in the metabolic pathways of the following three biomolecules：Fatty acids,amino acids,and lipids.The receiver operating characteristic curves of3D,7D,and 11D-phytanic acid,behenic acid,and threoninyl-γ-glutamate exhibited excellent efficiency with area under the curve （AUC） values of 0.904 （95% confidence interval [CI]：0.863-0.944）,0.93 （95% CI：0.893-0.966）,and 0.964 （95% CI：0.941-0.988）,respectively.The largest and smallest resulting AUCs were 0.964 and 0.720,indicating that these biomarkers may be involved in the disease mechanisms.The combination of lysophosphatidylcholine （18∶0）,behenic acid,threoninyl-γ-glutamate,and presqualene diphosphate was used to represent the most suitable biomarker group for the differentiation of patients with TB active from the control subjects,with an AUC value of 0.991.Conclusion：The metabolic analysis results identified new serum biomarkers that can distinguish TB from non-TB diseases.The metabolomics-based analysis provides specific insights into the biology of TB and may offer new avenues for TB diagnosis.
文摘Objective:To study the differences between the serum metabolites in patients with adenomatous polyps of the colon and yang-deficiency constitution and those without colon polyps and with balanced constitution,and look for biomarkers that can be used to distinguish between the two groups.Methods:General patient information was gathered,and Chinese medicine constitutions were collected in 940 patients who underwent electronic colonoscopy.A total of 119 patients with adenomatous polyps of the colon and yang-deficiency constitution were included in the experimental group,and 150 patients without colon polyps and with balanced constitution were included in the control group.Metabolomics analysis was performed on the fasting venous blood obtained from each patient in both groups.Principal component analysis and orthogonal partial least squares discriminant analysis were performed on the detection results,potential biomarkers were screened,metabolic pathway changes were determined,and the metabolic processes involved were discussed.Results:A total of 59 differential biomarkers between the experimental group and the control group were identified.The differential metabolites were found mainly in the glycerophospholipid metabolism pathway,and the bile acid 3-oxo-4,6-choladienoic acid was the biomarker that distinguished the experimental group from the control group.Conclusions:With the help of metabolomics analysis,the differential metabolites in patients with adenomatous polyps of the colon and yang-deficiency constitution and those in patients without colon polyps and with balanced constitution could be identified.The biomarker 3-oxo-4,6-choladienoic acid may have potential diagnostic value in patients with adenomatous polyp of the colon and yang-deficiency constitution.(Trial Registration No.NCT02986308)
基金supported by the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” 2015ZX09501004-001-007National Natural Science Foundation of China 82004082Top talent training project of TCM in Henan Province。
文摘Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule(NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice;during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix Win Nonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in C_(max) of ferulic acid and formononetin, AUC_(all) of caffeic acid and ferulic acid, and AUC_(INF_obs) of ferulic acid. Conversely, an increase in the Vz_F_obs and MRT_(last) of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.
基金supported by the National Key Research and Development Project(SQ2018YPC170480,2018YFC1708202)the National Natural Science Foundation of China(81774009)+1 种基金the Key science and technology projects of Inner Mongolia Autonomous Region(2019ZD004)Open Project Program of Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology,China(MDK 2019040)。
文摘Objective:There are different geographic origins of Aconiti Kusnezoffii Radixs(AKRs)sold in the market with different quality.This study aims to establish a rapid analysis method to distinguish the different geographic origins of AKRs and to realize the rapid evaluation of their quality.Methods:An ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry(UPLC-Q-TOF MS)method was utilized to acquire the constituents'information of AKRs from different geographic origins.MSE data and Progenesis QI software were employed to identify the chemical constitutes.Principal component analysis(PCA)was applied to comparing MS data to find the chemical markers of AKRs from different geographic origins.Results:Twenty-three components were detected and 17 out of them were identified,including diester-diterpenoid alkaloids,monoester-diterpenoid alkaloids,and amine-diterpenoid alkaloids.Three pairs of isomers were detected and two of them were distinguished by the retention time of standard samples.Thirteen chemical markers were screened out through PCA and orthogonal partial least square discriminant analysis.Through detecting Napelline or isomer of Napelline(m/z 360.2530)and Aconifine(m/z 662.3170),AKRs from inner Mongolia autonomous could be screened.According to the existence of benzoylaconine(m/z 604.3108)and Indaconitine(m/z 630.3159),it could be confirmed that the AKRs are from Xinjiang Uygur autonomous.AKRs that cannot detect compounds above-mentioned could be from Liaoning or Shanxi Province.Conclusions:The chemical profile could be used not only to distinguish the AKRs from different geographic origins but also to identify the true and false of AKRs.This study lays a foundation for the study of efficacy and toxic of AKRs.
基金supported financially by the National Natural Science Foundation of China (Grant No. 81973604, 81803690and 81703684)the Innovative Talents Funding of Heilongjiang University of Chinese Medicine(Grant No.2018RCD25)+8 种基金the National natural science foundation matching project (Grant No. 2018PT02)the National natural Science Foundation Matching Project (Grant No. 2017PT01)the Graduate Innovative Research Project Foundation of Heilongjiang University of Chinese Medicine (Grant No. 2019yjscx013)the Postdoctoral Initial Fund of Heilongjiang Provincethe University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (Grant No. UNPYSCT2017215 and UNPYSCT2017219)the Natural Science Foundation of Heilongjiang Province (Grant No. H2015037)the Heilongjiang University of Chinese Medicine Doctoral Innovation Foundation (Grant No. 2014bs05)the Application Technology Research and Development Projects of Harbin Technology Bureau (Grant No. 2014RFQXJ149)Heilongjiang Postdoctoral Scientific Research Developmental Fund (Grant No.LBHQ16210 and LBH-Q17161)
文摘A rapid and high selective ultra-performance liquid chromatography(UPLC)with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin,paeoniflorin,picroside I,picroside II,saikosaponin A,and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard.One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples.Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column(100 mm×2.1 mm,1.7μm)at a flow rate of 0.4 m L/min,using gradient mode containing 0.1%formic acid in water and acetonitrile were used as the Mobile phase A and B.Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components.Calibration curves showed good linearity(R^2>0.9908)over a wide concentration range for all compounds.The intra-and interday precision(relative standard deviation)ranged 2.4%–7.0%and 2.6%–8.0%,respectively.The accuracy(relative error)was from-13.0%to 13.2%at all quality control levels.The recovery ranged from 81.1%to 92.5%.The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan-Shu Yu-Fang.The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.
基金financially supported by the National Natural Science Foundation of China (81673598, 81973483, 82003948)Natural Science Foundation of Zhejiang Province (LQ21H280002)+3 种基金The National Key Research and Development Program of China (2018YFC1707000)the National traditional Chinese medicine industry special project (2015468002-2)National Standardization Program for Chinese Medicine (ZYBZH-Y-SC-40)Zhejiang Chinese Medicine University School-level Scientific Research Fund for Talents (2020ZR14)。
文摘Background: Curcuma wenyujin rhizome(CWR) is a commonly used Chinese herbal medicine for treating blood stasis in China for 1000 of years. However, the underlying mechanism of CWR remains unclear. Aims and Objectives: The purpose of this study is to clarify the bioactive mechanism of CWR in treating blood stasis. Materials and Methods: In this study, pharmacological indexes, including hemorheology and four blood coagulation indexes were tested. Bile and urine metabolomics were engaged by UPLC-Q/TOF-MS. Multivariate statistical analysis were used to screen out differential endogenous metabolites. Results: The results indicated that CWR significantly ameliorated the hemorheology and coagulation functions of acute blood stasis(ABS) model rats. Moreover, 27 endogenous metabolites between the CWR group and the ABS group were screened, and the levels were all improved to certain degrees by CWR preadministration. Metabonomics results indicated that ABS was mainly related to linoleic acid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism, pentose and glucuronate intercereasonversions, steroid hormone biosynthesis, and primary bile acid biosynthesis. Conclusion: In a word, the metabolomics method is consistent with the holistic view of traditional Chinese medicine(TCM) that can be a powerful means to illustrate the biological activity mechanism of CWR in treating blood stasis and to offer research demonstration for further study on the effector mechanism of TCM.
基金supported by the National Natural Science Foundation of China,No.82101327(to YY)President Foundation of Nanfang Hospital,Southern Medical University,No.2020A001(to WL)+1 种基金Guangdong Basic and Applied Basic Research Foundation,Nos.2019A1515110150,2022A1515012362(both to YY)Guangzhou Science and Technology Project,No.202201020111(to YY).
文摘Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.
基金the National Natural Science Foundation of China:Effects of Hawthorn Leaves Flavonoids on Atherosclerosis Unstable Plaques based on the Mechanism of Liver-gut axis Liver X Receptor (LXR-a)-mediated Iron and Lipid Metabolism Disorders (No.82260794)the Natural Science Foundation of Jiangxi Province:based on Secreted Phospholipase A2 TypeⅡA (sPLA2-ⅡA) Regulating Lipid Mediated Foam Cell Formation to Explore the Effect and Molecular Mechanism of Hawthorn Leaf Flavonoids on Antiatherosclerosis (No.20212BAB206013)+1 种基金the Key R&D Program of Jiangxi Province:Research on the Quality Enhancement and Industrialization Technology Improvement of the Lipid-Lowering Traditional Chinese Medicine"Hedan Tablet"(No.20201BBG71005)Science and Technology Project of Jiangxi Provincial Department of Education:based on the"Phlegm-Stasis"Theory to Explore the Effects and Molecular Mechanisms of Hawthorn Leaves Flavonoids on Improving Iron and Lipid Metabolism Disorders in Atherosclerosis (No.GJJ2203502)。
文摘OBJECTIVE:To examine Hedan tablet(HDT,荷丹片)'s potential mechanisms in hyperlipidemic rats induced by a high-fat diet(HFD),as well as its regulatory effects and primary active constituents.METHODS:By using ultra-performance liquid chromatography(UPLC)-quadrupole-time-of-flight(QTOF)-tandem mass spectrometry(MS/MS),the components of HDT that can enter the circulatory system were found,aiming to investigate its active constituents with pharmacological effects.Based on network pharmacology approaches,the relevant HDT targets in the therapy of hyperlipidemia were anticipated.The possible mechanism of HDT for hyperlipidemia treatment was verified by in-vivo experiments,and the main active components of HDT for hyperlipidemia treatment were analyzed via in-vitro experiments.RESULTS:UPLC-QTOF-MS/MS identified 30 components of HDT entering the circulatory system,primarily consisting of flavonoids,diterpenoids and alkaloids.The results of a network pharmacology study revealed that 30 active components mostly target 74 genes associated with hyperlipidemia.The primary active ingredients may include quercetin,kaempferol,and epicatechin,and the main gene targets may be tumor necrosis factor(TNF),interleukin-6(IL-6),interleukin 1 beta(IL-1β),etc.The results of animal experiments demonstrated that HDT can significantly regulate the blood lipid level in rats with HFD,improve the degree of inflammatory infiltration in rat liver cells,lower TNF-α,Creactive protein(CRP),IL-6,matrix metalloproteinase 9(MMP9) and malondialdehyde(MDA) levels while raising total superoxide dismutase(T-SOD) level.Meanwhile,HDT can considerably lower the expression of sterol regulatory element-binding transcription factor 2(SREBF2),3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR),and MMP9 while significantly increasing the expression of peroxisome proliferator-activated receptor alpha(PPAR-α) and PPAR-γ.In vitro study confirmed that quercetin and kaempferol could reduce the levels of IL-6,IL1B,MMP9 and HMGCR in the high-fat model of hepatoma G2 cells.CONCLUSIONS:The mechanism by which HDT treats hyperlipidemia involves modification of the lipid metabolism targets such as downregulating SREBF2,HMGCR and MMP9,and upregulating PPAR-α and PPAR-γ,as well as anti-inflammatory and antioxidant actions.This study provides a pharmacological and biological rationale for the use of HDT in clinical hyperlipidemia management.
基金National Natural Science Foundation of China(Grant No.30630073)
文摘XiaoShuanTongLuo （XSTL） is an important multi-herbal formula widely used as a traditional Chinese medicine （TCM）. In this paper, an ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric method （UPLC-ESI-MS/MS） was developed for the simultaneous identification and quantification of 18 chemical constituents in the extract of XSTL. The analysis was performed in multiple-reaction monitoring （MRM） mode using positive and negative electrospray ionization （ESI）. A BEH C18 （2.1 mm× 100 mm, 1.7 μm） column with a gradient mobile phase of methanol-0.1% aqueous formic acid solution at a flow rate of 0.2 mL/min was used for separation. The standard curves of most components showed good linearity over the concentration range of 0.001-0.5 μg/mL with r = 0.9896-0.9996. The relative standard deviations （RSD） of intra-day and inter-day precision were all lower than 15% at low, middle, and high concentration levels. The RSD of stability analysis in 24 h were also lower than 15%. The validated method was employed to quantify 18 active components simultaneously in four different commercial brands of XSTL products in various dosage forms. The developed method was rapid, accurate, sensitive, and reproducible for the quality control of XSTL.
文摘To establish a rapid and effective method for analysis and identification of the alkaloids from Ranunculus japoni- cus Thunb by ultra-performance liquid chromatogaraphy with quadruple-time-of-flight mass spectrometry （UPLC/Q-TOF- MS） and discuss their fragmentation regularity, the UPLC/Q-TOF-MS was used to identify the alkaloids from Ranunculus japonicus Thunb by their MS data, tandem characteristic fragment ions and standards. In the end, 12 alkaloids were identi- fied from Ranunculus japonicus for the first time, and their fragmentation regularity was discussed. Thus, a rapid and effec- tive analysis and identification method for the alkaloids from Ranunculus japonicus by UPLC/Q-TOF-MS is established.
基金support from the National Natural Science Foundation of China(No.51905034)。
文摘There exists an increasing need for precision measurement&pointing control and extreme motion stability for current and future space systems,e.g.,Ultra-Performance Spacecraft(UPS).Some notable technologies of realizing Ultra-Pointing(UP)ability have been developed particularly for Ultra-accuracy Ultra-stability Ultra-agility(3 U)spacecraft over recent decades.Usually,Multilevel Compound Pointing Control Techniques(MCPCTs)are deployed in aerospace engineering,especially in astronomical observation satellites and Earth observation satellites.Modern controllers and/or algorithms,which are a key factor of MCPCTs for 3 U spacecraft,especially the jitter phenomena that commonly exist in a UPS Pointing Control System(PCS),have also been effectively used in some UP spacecraft for a number of years.Micro-vibration suppression approaches,however,are often proposed to deal with low-level mechanical vibration or disturbance in the microgravity environment that is common for UPS.This latter approach potentially is one of the most practical UP techniques for 3 U tasks.Some emerging advanced Disturbance-Free Payload(DFP)satellites that exploit the benefits of non-contact actuators have also been reported in the literature.This represents an interesting and highly promising approach for solving some challenging problems in the area.This paper serves as a state-of-the-art review of UP technologies and/or methods which have been developed,mainly over the last decade,specifically for or potentially could be used for 3 U spacecraft pointing control.The problems discussed in this paper are of reference significance to UPS and millisecond optical sensors,which are involved in Gaofeng Project,deep space exploration,manned space flight,and gravitational wave detection.
基金Supported by the Stem Cell and Translational Research,the National Key Research and Development Program of China,No.2016YFA0101001Independent Project Fund of the State Key Laboratory for Diagnosis and Treatment of Infectious Disease(SKL DTID)
文摘BACKGROUND Fibrosis is the single most important predictor of significant morbidity and mortality in patients with chronic liver disease.Established non-invasive tests for monitoring fibrosis are lacking,and new biomarkers of liver fibrosis and function are needed.AIM To depict the process of liver fibrosis and look for novel biomarkers for diagnosis and monitoring fibrosis progression.METHODS CCl4 was used to establish the rat liver fibrosis model.Liver fibrosis process was measured by liver chemical tests,liver histopathology,and Masson’s trichrome staining.The expression levels of two fibrotic markers includingα-smooth muscle actin and transforming growth factorβ1 were assessed using immunohistochemistry and real-time polymerase chain reaction.Dynamic changes in metabolic profiles and biomarker concentrations in rat serum during liver fibrosis progression were investigated using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.The discriminatory capability of potential biomarkers was evaluated by receiver operating characteristic(ROC)curve analysis.RESULTS To investigate the dynamic changes of metabolites during the process of liver fibrosis,sera from control and fibrosis model rats based on pathological results were analyzed at five different time points.We investigated the association of liver fibrosis with 21 metabolites including hydroxyethyl glycine,L-threonine,indoleacrylic acid,β-muricholic acid(β-MCA),cervonoyl ethanolamide(CEA),phosphatidylcholines,and lysophosphatidylcholines.Two metabolites,CEA andβ-MCA,differed significantly in the fibrosis model rats compared to controls(P<0.05)and showed prognostic value for fibrosis.ROC curve analyses performed to calculate the area under the curve(AUC)revealed that CEA andβ-MCA differed significantly in the fibrosis group compared to controls with AUC values exceeding 0.8,and can clearly differentiate early stage from late stage fibrosis or cirrhosis.CONCLUSION This study identified two novel biomarkers of fibrosis,CEA andβ-MCA,which were effective for diagnosing fibrosis in an animal model.
基金Chinese Academy of Agricultural Sciences(Grant No.125161015000150013)the grants from the China Agriculture Research System(Grant No.CARS-21).
文摘We investigated the antidepressant-like activity of Hemerocallis citrine Baroni extract(HCE)in a simulated microgravity(SMG)-induced rat model of depression using a metabolomics method.A rat model,generated via 14 d of SMG induction,was validated from the reduced sucrose preference and the enhanced immobility time in the forced swimming test.HCE and paroxetine reversed certain metabolite profiles.Anti-depressant effects of HCE might involve the regulation of several metabolic pathways,such as phenylalanine,glutamic acid,and tryptophan metabolism and changes in energy metabolism.5-Hydroxytryptophan,hippuric acid,phenylacetylglycine,citric acid,3-hydroxykynurenine,cyclic AMP,and L-DOPA profiles were altered upon HCE and paroxetine administration.Furthermore,glutamic acid was only regulated in the HCE group,while xanthurenic acid and deoxyuridine were reversed in the positive group,suggesting differences in the mechanisms between the positive drugs and HCE in improving glutamic acid metabolism.This study provided a theoretical foundation for the application of HCE in depression therapy.
基金Key Research and Development Project of Department of Science and Technology of Hunan Province(2022GK4015)Natural Science Foundation of Hunan Province(2021JJ30562)Postgraduate Research Innovation Project of Hunan University of Chinese Medicine(2021CX62)。
文摘Objective To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides(PSP)against kidney aging in D-galactose(D-gal)-induced aging mice,based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive MS/MS).Methods A total of 36 C57 BL/6J mice were randomly allocated to six groups:control(CON),model(MOD),PSP low-dose(PSP-L),PSP medium-dose(PSP-M),PSP high-dose(PSP-H),and positive drug ascorbic acid(VC)groups.To create models of aging mice,D-gal was intraperitoneally administered to all other groups of mice except the CON group.After modeling,the appropriate Chinese medicine[PSP-L:150 mg/(kg·d),PSP-M:300 mg/(kg·d),PSP-H:600 mg/(kg·d)]or positive drug[ascorbic acid,300 mg/(kg·d)]was administered for intervention.Key markers of renal function in urine and serum of mice in each group,such as creatinine(Crea),urea nitrogen(BUN),and uric acid(UA)levels,as well as key indicators of oxidative stress in serum and kidney,including superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA),and glutathione peroxidase(GSH-Px)were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP.Hematoxylin and eosin(HE),periodic acid Schiff(PAS),andβ-galactosidase staining were used to assess the renal pathological changes.The metabolic profiles of serum,kidney,and urine samples from CON,MOD,and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS,and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites.Results Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators.Following the injection of PSP[PSP-H:600 mg/(kg·d)],the pathological indices associated with aging were adjusted to normal levels,renal function and oxidative stress were improved in aging mice,and renal pathological damage was markedly improved.Meanwhile,the potential biomarkers were identified by UPLCQ-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways,with P<0.05 as a threshold.The results showed that purine,sphingolipid,glycerophospholipid,tryptophan,and riboflavin metabolisms were the main metabolic pathways associated with aging.After administration of PSP,these pathological indices returned to normal levels,and biomarkers related to the aging process,such as adenosine monophosphate(AMP),tryptophan,and 5-hydroxytryptophan,also demonstrated,to some degree,reverse regulation(promoting synthesis).Conclusion Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice.PSP has been shown to protect against kidney aging by interfering with the purine,sphingolipid,glycerophospholipid,tryptophan,and riboflavin metabolisms in the kidney.
