Although the current literature has recorded many reports of identifying components from herbal preparations, all of them were largely limited to target components. This paper provides a novel and generally applicable approach to identifying nontarget components from herbal preparations, based on the use of liquid chromatography ion trap time-of-flight mass spectrometry (LC/MS-IT-TOF). A simple program was originally developed for searching the common diagnostic ions from all experimentally generated ions. The components sharing the exact same ions (mass error < 5 mDa) were classified into a family. All families were then connected into a coherent network by the bridging components that are present in two or more families. With the benefit from such a network, it is feasible to sequentially characterize the structures of all diagnostic ions once a single component has been de novo identified. The structures of the diagnostic ions could then be used as "a priori" information for selecting the exact candidates containing the substructures of the corresponding diagnostic ions from the primary database hits. This strategy enables a nearly 7-fold narrowing of the database hits and thus substantially enhances the analytical efficiency and sharpness. With the use of such an approach, 43 out of 53 components incorporated into the network have been successfully identified from the test herbal preparation. For the rest, components failed to be identified using this approach; a complementary approach to screening by sequential loss of specific chemical groups, proposed from the accurate mass differences between fragments, was established to narrow the database hits. All of the 87 peaks detected have been successfully identified by combining the use of both approaches except failed to differentiate some isomers. The presently developed approach and methodology would be useful for the identifications of complicated nontarget components from various complex mixtures such as herbal preparations, biological, and environmental samples.

Slug (Snai2) has been demonstrated to act as an oncogene or tumor suppressor in different human cancers, but the function of Slug in cervical cancer remains poorly understood. In this study, we demonstrated that Slug could suppress the proliferation of cervical cancer cells in vitro and tumor formation in vivo. Further experiments found that Slug could trans-suppress the expression of Akt1/p-Akt1 by binding to E-box motifs in the promoter of the Akt1 gene and then inhibit the cell proliferation and tumor formation of cervical cancer cells by up-regulating p21/p27 and/or down-regulating the activity of the Wnt/β-catenin signaling pathway. Therefore, Slug acts as a tumor suppressor during cervical carcinogenesis.

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HOXA5 is considered a regulator involved in embryonic development and cellular differentiation and a tumor suppressor. Nevertheless, its biological role in cervical carcinoma is still unclear. In the present study, immunohistochemistry showed that HOXA5 expression gradually decreased as the degree of cervical lesions deepened. Ectopic expression of HOXA5 restrained cell proliferation, decreased cell viability, and inhibited tumor formation in vitro and in vivo. Furthermore, the expression of HOXA5 could arrest cell cycle from G0/G1 to S phase. RNA-seq revealed that p21 and cyclinD1 were involved in this process. Moreover, the gene set enrichment analysis and the TOP/FOP reporter assay both suggested that HOXA5 could restrain the activity of the Wnt/β-catenin pathway. Further study using dual-luciferase reporter assay and quantitative chromatin immunoprecipitation assay demonstrated that HOXA5 could directly bind to the TAAT motif within the promoter of TP53 by its HD domain and transactivate TP53, which can upregulate p21. Altogether, our data suggest that HOXA5 inhibits the proliferation and neoplasia via repression activity of the Wnt/β-catenin pathway and transactivating TP53 in cervical cancer.

The article examines the effect of bicultural framing strategy on the evaluation of culturally mixed products (CMPs). Across two experiments, we demonstrate a self–other asymmetry effect in the CMP evaluation. Specifically, we examine the “foreign-culture home-culture” strategy in which the foreign culture “modifies” the home culture. This phenomenon leads to less favorable evaluation of CMPs relative to the “home-culture foreign-culture” strategy in which the home culture “modifies” the foreign culture. Furthermore, the findings show that consumers’ perception of cultural intrusion mediates the effect of framing strategy on CMP evaluation. We also identify the boundary condition wherein the self–other asymmetry is attenuated when people focus their judgment on facts (as opposed to motivation).

Global metabolite identification of complex compound mixtures in biological systems is a very challenging task. Herein, we developed and validated a chemicalome to metabolome matching approach by taking herbal medicine as an example to delineate the metabolic networks of complex systems. This approach consists of five steps of data processing including raw data output, endogenous background subtraction, parent compound and metabolite differentiation, chemicalome to metabolome correlation, and the final validation via manual fragment comparison. Chemicalome to metabolome correlation, the core step of this approach, was performed based on matching the accurate mass differences of pseudomolecular ions between them with the accurate mass changes of known metabolic pathways and validating the matches by validation ions. A step-forward approach that confers a gradual identification of metabolites generated from different steps (1-4) and types (degradation, phase I/II, or mixed) of metabolic reactions was further proposed for chemicalome to metabolome matching. This approach was validated to be very useful and powerful for the metabolite identification of a single compound, a homologous compound mixture, and a complex herbal system. Using this approach, all metabolites (162) detected from urine samples of rats treated with Mai-Luo-Ning injection could be linked to their respective parent compounds, and 143 of them were supported by the final validation via manual fragment analysis. In most cases, more than 80% of the automatic matching results could be supported by the manual fragment validations. A complex metabolic network showing all the possible links between precursors and metabolites was successfully constructed. This study provides a generally applicable approach to global metabolite identification of complex compound mixtures in complex matrixes.

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BackgroundCatastrophic health expenditure (CHE) puts a heavy disease burden on patients’ families, aggravating income-related inequality. In an attempt to reduce the financial risks of rural families incurring CHE, China began the New Rural Cooperative Medical System (NCMS) on a trial basis in 2003 and has raised the reimbursement rates continuously since then. Based on statistical data about rural families in sample area of Jiangsu province, this study measures the incidence of CHE, analyzes socioeconomic inequality related to CHE, and explores the influences of the NCMS on the incidence of CHE.MethodsStatistical data were acquired from two surveys about rural health care, one conducted in 2009 and one conducted in 2010. In 2009, 1424 rural families were analyzed; in 2010, 1796 rural families were analyzed. An index of CHE is created to enable the evaluation of the associated financial risks. The concentration index and concentration curve are used to measure the income-related inequality involved in CHE. Multiple logistic regression is utilized to explore the factors that influence the incidence of CHE.ResultsThe incidence of CHE decreased from 13.62% in 2009 to 7.74% in 2010. The concentration index of CHE was changed from −0.298 (2009) to −0.323 (2010). Compared with rural families in which all members were covered by the NCMS, rural families in which some members were not covered by the NCMS had a lower incidence of CHE: The odds ratio is 0.65 with a 95% confidence interval of 0.43 to 1.00. For rural families in which all members were covered by the NCMS, the increase in reimbursement rates is correlated to the decline in the incidence of CHE if other influencing factors were controlled: The odds ratio is 0.48 with a 95% confidence interval of 0.36 to 0.64.ConclusionsBetween 2009 and 2010, the incidence rate of CHE in the sampled area decreased sharply, CHE was more concentrated among least wealthy and inequality increased during study period. As of 2010, the poorest rural families still had high risk of experiencing CHE. For rural families in which all members are covered by the NCMS, the rise in reimbursement rates reduces the probability of experiencing CHE.Electronic supplementary materialThe online version of this article (10.1186/s12889-017-4713-x) contains supplementary material, which is available to authorized users.