The dynamic metabolic profile of Qi-Yu-San-Long decoction in rat urine using UPLC-QTOF-MS^(E) coupled with a post-targeted screening strategy

Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolicrelated studies on QYSLD have not been performed.In this study,a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full information tandem mass spectrometry(UPLC-QTOF-MS^(E))was developed to identify QYSLD-related xenobiotics in rat urine.The chemical compound database of QYSLD constituents was established from previous research,and metabolites related to these compounds were predicted in combination with their possible metabolic pathways.The metabolites were identified by extracted ion chromatograms using predicted m/z values as well as retention time,excimer ions,and fragmentation behavior.Overall,85 QYSLD-related xenobiotics(20 prototype compounds and 65 metabolites)were characterized from rat urine.The main metabolic reactions and elimination features of QYSLD included oxidation,reduction,decarboxylation,hydrolysis,demethylation,glucuronidation,sulfation,methylation,deglycosylation,acetylation,and associated combination reactions.Of the identified molecules,14 prototype compounds and 58 metabolites were slowly eliminated,thus accumulating in vivo over an extended period,while five prototypes and two metabolites were present in vivo for a short duration.Furthermore,one prototype and five metabolites underwent the process of“appearing-disappearing-reappearing”in vivo.Overall,the metabolic profile and characteristics of QYSLD in rat urine were determined,which is useful in elucidating the active components of the decoction in vivo,thus providing the basis for studying its mechanism of action.

Dynamic simulation of urban water metabolism under water environmental carrying capacity restrictions

A revised concept for urban water metabolism （UWM） is presented in this study to address the inadequacies in current research on UWM and the problems associated with the traditional urban water metabolic process. Feedback loops can be analyzed to increase the water environmental carrying capacity （WECC） of the new urban water metabolism system （UWMS） over that of a traditional UWMS. An analysis of the feedback loops of an UWMS was used to construct a system dynamics （SD） model for the system under a WECC restriction. Water metabolic processes were simulated for different scenarios using the Tongzhou District in Beijing as an example. The results for the newly developed UWM case showed that a water environment of Tongzhou District could support a population of 1.1926 × 106, an irrigation area of 375.521 km2, a livestock of 0.7732 × 106, and an industrial value added of ￥193.14 × 109 （i.e. about US$28.285 × 109） in 2020. A sensitivity analysis showed that the WECC could be improved to some extent by constructing new sewage treatment facilities or by expanding the current sewage treatment facilities, using reclaimed water and improving the water circulation system.

Trimester-specific urinary metabolome alterations associated with gestational diabetes mellitus:A study in different pregnancy stages

Gestational diabetes mellitus(GDM),a frequently-occurring disease during pregnancy,may cause some adverse healthy outcome of both mother and offspring.However,the knowledge about metabolite alterations during the pathogenesis and development process is limited.Here,a large longitudinal nontargeted metabolomics study of 195 pregnant women(64 women with subsequently developed GDM and131 healthy controls)was conducted.Each participant provided urine samples at three timepoints during early,middle and late pregnancy,respectively.The metabolic profiles of 585 urine samples(195×3)were measured by using ultra-high performance liquid chromatography coupled with Orbitrap high-resolution mass spectrometry.Among the 56 identified metabolites,the levels of eight metabolites increased and three ones decreased in the first trimester,the concentration of one metabolite increased and those of 20 decreased in the second trimester,as well as the levels of five metabolites increased and two decreased in the third trimester.After false discovery rate correction,the levels of valine and 5-acetamidovalerate in GDM group significantly increased in the first trimester,the levels of 1-methylguanine and 1,3-dihydro-(2 H)-indol-2-one significantly decreased in the second trimester and three metabolites(threonine,OH-octanedioyl-carnitine and pimelylcarnitine)increased and N-acetyltryptophan decreased in the third trimester,respectively.Six metabolites,such as pantothenic acid and threonine,had significant interaction effects between gestational stage(different trimester)and group(GDM or control).The differential metabolites were involved in“tryptophan metabolism”,“purine metabolism”,“valine,leucine and isoleucine degradation”and other pathways.The findings may provide insights into further pathogenesis study of GDM.