A novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive malignancies with increasing incidence worldwide. The oncogenic roles of transcription factors (TFs) were increasingly recognized in various cancers. This study aimed to develop a predicting signature based on TFs for the prognosis and treatment of HCC.Methods: Differentially expressed TFs were screened from data in the TCGA-LIHC and ICGC-LIRI-JP cohorts. Univariate and multivariate Cox regression analyses were applied to establish a TF-based prognostic signature. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the signature. Subsequently, correlations of the risk model with clinical features and treatment response in HCC were also analyzed. The TF target genes underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, followed by protein-protein-interaction (PPI) analysis.Results: A total of 25 differentially expressed TFs were screened, 16 of which were related to the prognosis of HCC in the TCGA-LIHC cohort. A 2-TF risk signature, comprising high mobility group AT-hook protein 1 (HMGA1) and MAF BZIP transcription factor G (MAFG), was constructed and validated to negatively related to the overall survival (OS) of HCC. The ROC curve showed good predictive efficiencies of the risk score regarding 1-year, 2-year and 3-year OS (mostly AUC >0.60). Additionally, the risk score independently predicted OS for HCC patients both in the training cohort of TCGA-LIHC dataset (HR = 2.498, p = 0.007) and in the testing cohort of ICGC-LIRI-JP dataset (HR = 5.411, p < 0.001). The risk score was also positively correlated to progressive characteristics regarding tumor grade, TNM stage and tumor invasion. Patients with a high-risk score were more resistant to transarterial chemoembolization (TACE) treatment and agents of lapatinib and erlotinib, but sensitive to chemotherapeutics. Further enrichment and PPI analyses demonstrated that the 2-TF signature distinguished tumors into 2 clusters with proliferative and metabolic features, with the hub genes belonging to the former cluster.Conclusion: Our study identified a 2-TF prognostic signature that indicated tumor heterogeneity with different clinical features and treatment preference, which help optimal therapeutic strategy and improved survival for HCC patients

Intervening Effects of Total Alkaloids of Corydalis saxicola Bunting on Rats With Antibiotic-Induced Gut Microbiota Dysbiosis Based on 16S rRNA Gene Sequencing and Untargeted Metabolomics Analyses

Gut microbiota dysbiosis induced by antibiotics is strongly connected with health concerns. Studying the mechanisms underlying antibiotic-induced gut microbiota dysbiosis could help to identify effective drugs and prevent many serious diseases. In this study, in rats with antibiotic-induced gut microbiota dysbiosis treated with total alkaloids of Corydalis saxicola Bunting (TACS), urinary and fecal biochemical changes and cecum microbial diversity were investigated using 16S rRNA gene sequencing analysis and untargeted metabolomics. The microbial diversity results showed that 10 genera were disturbed by the antibiotic treatment, and two of them were obviously restored by TACS. The untargeted metabolomics analysis identified 34 potential biomarkers in urine and feces that may be the metabolites that are most related to the mechanisms underlying antibiotic-induced gut microbiota dysbiosis and the therapeutic effects of TACS treatment. The biomarkers were involved in six metabolic pathways, comprising pathways related to branched-chain amino acid (BCAA), bile acid, arginine and proline, purine, aromatic amino acid, and amino sugar and nucleotide sugar metabolism. Notably, there was a strong correlation between these metabolic pathways and two gut microbiota genera (g__Blautia and g__Intestinibacter). The correlation analysis suggested that TACS might synergistically affect four of these metabolic pathways (BCAA, bile acid, arginine and proline, and purine metabolism), thereby modulating gut microbiota dysbiosis. Furthermore, we performed a molecular docking analysis involving simulating high-precision docking and using molecular pathway maps to illuminate the way that ligands (the five main alkaloid components of TACS) act on a complex molecular network, using CYP27A1 (a key enzyme in the bile acid synthesis pathway) as the target protein. This study provides a comprehensive overview of the intervening effects of TACS on the host metabolic phenotype and gut microbiome in rats with gut microbiota dysbiosis, and it presents new insights for the discovery of effective drugs and the best therapeutic approaches

An optimized microwave-assisted extraction method for increasing yields of rare ginsenosides from Panax quinquefolius L.

AbstractBackgroundRare ginsenosides in Panax quinquefolius L. have strong bioactivities. The fact that it is hard to obtain large amounts of rare ginsenosides seriously restricts further research on these compounds. An easy, fast, and efficient method to obtain different kinds of rare ginsenosides simultaneously and to quantify each one precisely is urgently needed.MethodsMicrowave-assisted extraction (MAE) was used to extract nine kinds of rare ginsenosides from P. quinquefolius L. In this article, rare ginsenosides [20(S)-Rh1, 20(R)-Rh1, Rg6, F4, Rk3, 20(S)-Rg3, 20(R)-Rg3, Rk1, and Rg5] were identified by high performance liquid chromatography (HPLC)–electrospray ionization–mass spectrometry. The quantity information of rare ginsenosides was analyzed by HPLC-UV at 203 nm.ResultsThe optimal conditions for MAE were using water as solvent with the material ratio of 1:40 (w/v) at a temperature of 145°C, and extracting for 15 min under microwave power of 1,600 W. Seven kinds of rare ginsenosides [20(S)-Rh1, 20(R)-Rh1, Rg6, F4, Rk3, Rk1, and Rg5] had high extraction yields, but those of 20(S)-Rg3 and 20(R)-Rg3 were lower. Compared with the conventional method, the extraction yields of the nine rare ginsenosides were significantly increased.ConclusionThe results indicate that rare ginsenosides can be extracted effectively by MAE from P. quinquefolius L. in a short time. Microwave radiation plays an important role in MAE. The probable generation process of rare ginsenosides is also discussed in the article. It will be meaningful for further investigation or application of rare ginsenosides

Many Panels

Data and Analysis Scripts to the Many Panels Projec

Many Panels 5

In this study, we aim to replicate the findings of Many Panels 1, 2, and 4, which show that the default, framing, sunk cost, and less-is-better effects are moderated by the FACE factors. In contrast to earlier iterations of the Many Panels project, we will measure the respondents' memory for the treatment and use that to measure the actual treatment effect. In addition to more elaborate measures of crystallized intelligence, we also use the fluid intelligence measures of Many Panels 3, that are less influenced by experience

Many Panels

Data and Analysis Scripts to the Many Panels Projec

Development and validation of a PCR-RFLP / TaqMan MGB probe method for rapid sex identification of largemouth bass (Micropterus salmoides)

The largemouth bass (Micropterus salmoides) has become an important freshwater fish in China since it was intentionally introduced in the 1980 s, and the amount produced in aquaculture is increasing each year. Females are preferred because they grow faster than males and reach a larger body size. However, the physiological sex cannot be accurately determined from external morphology at the early growth stage, so it is crucial to develop sex-specific molecular markers. In this study, a single nucleotide polymorphism (SNP) marker was developed based on whole genome resequencing data obtained from 30 females and 30 males. This marker made it possible to positively identify male and female largemouth bass. Through Fst value screening, 123 SNP loci significantly associated with sex were obtained, and nearly 40% of them were located on chromosome 7 in a 3.44-Mb sex-linked region. A method of polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) combined with a TaqMan minor groove binder (MGB) probe was developed based on a sex-specific marker. Using this method, male and female fish in four different populations (n = 128) were identified with 100% accuracy. Compared with PCR-RFLP followed by electrophoretic separation of fragments, the PCR-RFLP–TaqMan MGB probe method reduced the time required to identify the sex of largemouth bass. The validation results also indicated that largemouth bass has an XX/XY sex-determination system. In conclusion, we have identified a sex-specific SNP marker for largemouth bass and developed a new technique to identify the sex of largemouth bass rapidly and accurately. These findings provide a scientific basis for further research on mono-sex breeding and the molecular mechanism of sex determination in largemouth bass

Probabilistic chip-collecting games with modulo winning conditions

Let $a$, $b$, and $n$ be integers with $0<a<b<n$. In a certain two-player probabilistic chip-collecting game, Alice tosses a coin to determine whether she collects $a$ chips or $b$ chips. If Alice collects $a$ chips, then Bob collects $b$ chips, and vice versa. A player is announced the winner when they have accumulated a number of chips that is a multiple of $n$. In this paper, we settle two conjectures from the literature related to this game