This study aimed to develop and validate a high-performance liquid chromatography system combined with a single-quadrupole Dalton mass detector for the separation and determination of pidotimod ((
R
...)-3-(
S
)-(5-oxo-2-pyrrolidinyl)carbonyl-thiazolidine-4-carboxylic acid) and its three isomers. The separations were achieved using a Lux Amylose-1 column operated at 40 °C using acetonitrile/0.1% trifluoroacetate (TFA) and isopropanol/0.1% TFA (90:10,
v
/
v
). The enantiorecognition mechanism was also elucidated using the ORCA 5 program. Four isomers were successfully separated with a resolution (Rs) > 1.5, with the method showing satisfactory linearity in the ranges of 0.2 to 3.5 μg·mL
−1
(
S,R; S,S
) and 0.5 to 3.5 μg·mL
−1
(
R,S; R,R
), along with good specificity, accuracy, and precision. Further, three batches of pidotimod oral solutions were evaluated and the
S,S
-isomer in each batch was detected at about 0.05%. Moreover, computational evaluations suggested that the sorbent-analyte interactions of amylose tris(3,5-dimethylphenycarbamate) can be used to successfully interpret and even predict the chromatographic separation results. The validated method showed high sensitivity and can potentially be used to analyze the isomer impurities of raw materials for quality control purposes.
Abstract
Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA–disease associations have received significant attention, no online repository is available to collect ...lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA–target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA–target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA–target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA–target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.
Estrogens in personal care products are harmful to customers. Conventional methods such as HPLC and LC-MS require tedious sample pretreatment and long analytical time. Paper-spray ionization mass ...spectrometry (PSI-MS) is a powerful tool for the determination of compounds with little time and minimal pretreatment procedures. Since most estrogens show poor responses in PSI-MS, we developed a chemical derivatization and PSI-MS method to determinate three estrogens: estradiol, estriol and ethinyloestradiol with estradiol valerate as the internal standard (I.S.). After derivatization with 2-fluoro-1-methyl-pyridinium-p-toluene-sulfonate, the three estrogens could be quantified in seconds. This method showed good linearity in the range of 0.1~30 μg·mL
, with R
> 0.999. Their recovery results were all between 85%~115%. The limits of detection (LOD) were 0.04 μg·mL
, 0.02 μg·mL
and 0.02 μg·mL
for estradiol, estriol and ethinyloestradiol respectively, which improved around 200, 2000, and 900 times compared to non-derivative PSI-MS. The method could quantitatively determine estrogens in cosmetics.
Circadian rhythm regulates complex physiological activities in organisms. A strong link between circadian dysfunction and cancer has been identified. However, the factors of dysregulation and ...functional significance of circadian rhythm genes in cancer have received little attention.
In 18 cancer types from The Cancer Genome Atlas (TCGA), the differential expression and genetic variation of 48 circadian rhythm genes (CRGs) were examined. The circadian rhythm score (CRS) model was created using the ssGSEA method, and patients were divided into high and low groups based on the CRS. The Kaplan-Meier curve was created to assess the patient survival rate. Cibersort and estimate methods were used to identify the infiltration characteristics of immune cells between different CRS subgroups. Gene Expression Omnibus (GEO) dataset is used as verification queue and model stability evaluation queue. The CRS model's ability to predict chemotherapy and immunotherapy was assessed. Wilcoxon rank-sum test was used to compare the differences of CRS among different patients. We use CRS to identify potential "clock-drugs" by the connective map method.
Transcriptomic and genomic analyses of 48 CRGs revealed that most core clock genes are up-regulated, while clock control genes are down-regulated. Furthermore, we show that copy number variation may affect CRGs aberrations. Based on CRS, patients can be classified into two groups with significant differences in survival and immune cell infiltration. Further studies showed that patients with low CRS were more sensitive to chemotherapy and immunotherapy. Additionally, we identified 10 compounds (e.g. flubendazole, MLN-4924, ingenol) that are positively associated with CRS, and have the potential to modulate circadian rhythms.
CRS can be utilized as a clinical indicator to predict patient prognosis and responsiveness to therapy, and identify potential "clock-drugs".
Aberrant expression of long non-coding RNAs (lncRNA) is associated with altered DNA methylation and histone modifications during carcinogenesis. However, identifying epigenetically dysregulated ...lncRNAs and characterizing their functional mechanisms in different cancer subtypes are still major challenges for cancer studies. In this study, we systematically analyzed the epigenetic alterations of lncRNAs at important regulatory elements in three breast cancer subtypes. We identified 87, 691, and 1,197 epigenetically dysregulated lncRNAs in luminal, basal, and claudin-low subtypes of breast cancer, respectively. The landscape of epigenetically dysregulated lncRNAs at enhancer elements revealed that epigenetic changes of the majority of lncRNAs occurred in a subtype-specific manner and contributed to subtype-specific biological functions. We identified six acetylation of lysine 27 on histone H3 (H3K27ac)-dysregulated lncRNAs and three DNA methylation-dysregulated lncRNAs (CTC-303L1.2, RP11-738B7.1, and SLC26A4-AS1) as prognostic biomarkers of basal subtype. These lncRNAs were involved in immune response-related biological functions. Treatment of the basal breast cancer cell line MDA-MB-468 with CREBBP/EP300 bromodomain inhibitors downregulated H3K27 acetylation levels and caused a decrease in the expression of five H3K27ac-dysregulated lncRNAs (LINC00393, KB-1836B5.1, RP1-140K8.5, AC005162.1, and AC020916.2) and inhibition of the growth of breast cancer cells. One epigenetically dysregulated lncRNA (LINC01983) and four lncRNA regulators (UCA1, RP11-221J22.2, RP11-221J22.1, and RP1-212P9.3) were identified as prognostic biomarkers of the luminal molecular subtype of breast cancer by controlling the tumor necrosis factor (TNF) signaling pathway, T helper (Th)17 cell differentiation, and T cell migration. Finally, our results highlighted a profound role of enhancer-related H3K27ac-dysregulated lncRNAs, DNA methylation-dysregulated lncRNAs, and lncRNA regulators in breast cancer subtype carcinogenesis and their potential prognostic value.
Display omitted
The corresponding authors and colleagues identified H3K27ac-dysregulated lncRNAs (LINC00393, KB-1836B5.1, RP1-140K8.5, AC005162.1, and AC020916.2) and DNA methylation-dysregulated lncRNAs (CTC-303L1.2, RP11-738B7.1, and SLC26A4-AS1) as prognostic biomarkers of basal subtypes. LINC01983, UCA1, RP11-221J22.2, RP11-221J22.1, and RP1-212P9.3 act as prognostic biomarkers of the luminal subtype. The inhibition of enhancer-related lncRNAs could suppress breast cancer cell growth.
Abstract
Differences in genetic molecular features including mutation, copy number alterations and DNA methylation, can explain interindividual variability in response to anti-cancer drugs in cancer ...patients. However, identifying genetic alteration-driven genes and characterizing their functional mechanisms in different cancer types are still major challenges for cancer studies. Here, we systematically identified functional regulations between genetic alteration-driven genes and drug target genes and their potential prognostic roles in breast cancer. We identified two mutation and copy number-driven gene pairs (
PARP1-ACSL1
and
PARP1-SRD5A3
), three DNA methylation-driven gene pairs (
PRLR-CDKN1C
,
PRLR
-
PODXL2
and
PRLR
-
SRD5A3
), six gene pairs between mutation-driven genes and drug target genes (
SLC19A1
-
SLC47A2
,
SLC19A1
-
SRD5A3
,
AKR1C3
-
SLC19A1
,
ABCB1
-
SRD5A3
,
NR3C2
-
SRD5A3
and
AKR1C3
-
SRD5A3
), and four copy number-driven gene pairs (
ADIPOR2
-
SRD5A3
,
CASP12-SRD5A3
,
SLC39A11
-
SRD5A3
and
GALNT2
-
SRD5A3
) that all served as prognostic biomarkers of breast cancer. In particular,
RARP1
was found to be upregulated by simultaneous copy number amplification and gene mutation. Copy number deletion and downregulated expression of
ACSL1
and upregulation of
SRD5A3
both were observed in breast cancers. Moreover, copy number deletion of
ACSL1
was associated with increased resistance to PARP inhibitors.
PARP1
-
ACSL1
pair significantly correlated with poor overall survival in breast cancer owing to the suppression of the MAPK, mTOR and NF-kB signaling pathways, which induces apoptosis, autophagy and prevents inflammatory processes. Loss of
SRD5A3
expression was also associated with increased sensitivity to PARP inhibitors. The
PARP1
-
SRD5A3
pair significantly correlated with poor overall survival in breast cancer through regulating androgen receptors to induce cell proliferation. These results demonstrate that genetic alteration-driven gene pairs might serve as potential biomarkers for the prognosis of breast cancer and facilitate the identification of combination therapeutic targets for breast cancers.
Pseudomonas stutzeri S116 is a sulfur-oxidizing bacteria isolated from marine sludge. It exhibited excellent electricity generation as bioanode and biocathode applied in microbial fuel cells (MFCs). ...Complete genome sequencing of P. stutzeri and cyclic voltammetry method were performed to reveal its mechanism in microbial fuel cells system.
This study indicated that the MFCs generated a maximum output voltage of 254.2 mV and 226.0 mV, and maximum power density of 765 mW/m
and 656.6 mW/m
respectively. Complete genome sequencing of P. stutzeri S116 was performed to indicate that most function genes showed high similarities with P. stutzeri, and its primary annotations were associated with energy production and conversion (6.84%), amino acid transport and metabolism (6.82%) and inorganic ion transport and metabolism (6.77%). Homology of 36 genes involved in oxidative phosphorylation was detected, which suggests the strain S116 possesses an integrated electron transport chain. Additionally, many genes encoding pilus-assembly proteins and redox mediators (riboflavin and phenazine) were detected in the databases. Thiosulfate oxidization and dissimilatory nitrate reduction were annotated in the sulfur metabolism pathway and nitrogen metabolism pathway, respectively. Gene function analysis and cyclic voltammetry indicated that P. stutzeri probably possesses cellular machinery such as cytochrome c and redox mediators and can perform extracellular electron transfer and produce electricity in MFCs.
The redox mediators secreted by P. stutzeri S116 were probably responsible for performance of MFCs. The critical genes and metabolic pathways involved in thiosulfate oxide and nitrate reduction were detected, which indicated that the strain can treat wastewater containing sulfide and nitrite efficiently.
This paper takes Macau souvenir packaging as the research object and explores the visual innovation of Macau souvenir packaging and its significance in cultural communication from the perspective of ...multicultural communication. The paper first introduces the background of Macau’s multiculturalism and the cultural value of Macau souvenir packaging, followed by an analysis of the impact and driving role of multicultural communication on the visual innovation of Macau souvenir packaging. The visual innovation of Macau souvenir packaging is analyzed from aspects such as patterns, colors, and design elements, using AI algorithms for validation and conducting visual innovation design for souvenir packaging. This paper provides valuable insights and references for the design and development of Macau souvenir packaging, contributing to the promotion of Macau souvenir packaging in cultural communication and the tourism industry.
Breast cancer is a cancer of high complexity and heterogeneity, with differences in prognosis and survival among patients of different subtypes. Copy number variations (CNVs) within enhancers are ...crucial drivers of tumorigenesis by influencing expression of their targets. In this study, we performed an integrative approach to identify CNA-driven enhancers and their effect on expression of target genes in four breast cancer subtypes by integrating expression data, copy number data and H3K27ac data. We identified 672, 555, 531, 361 CNA-driven enhancer-gene pairs and 280, 189, 113 and 98 CNA-driven enhancer-lncRNA pairs in the Basal-like, Her2, LumA and LumB subtypes, respectively. We then reconstructed a CNV-driven enhancer-lncRNA-mRNA regulatory network in each subtype. Functional analysis showed CNA-driven enhancers play an important role in the progression of breast cancer subtypes by influencing P53 signaling pathway, PPAR signaling pathway, systemic lupus erythematosus and MAPK signaling pathway in the Basal-like, Her2, LumA and LumB subtypes, respectively. We characterized the potentially prognostic value of target genes of CNV-driven enhancer and lncRNA-mRNA pairs in the subtype-specific network. We identified MUM1 and AC016876.1 as prognostic biomarkers in LumA and Basal-like subtypes, respectively. Higher expression of MUM1 with an amplified enhancer exhibited poorer prognosis in LumA patients. Lower expression of AC016876.1 with a deleted enhancer exhibited poorer survival outcomes of Basal-like patients. We also identified enhancer-related lncRNA-mRNA pairs as prognostic biomarkers, including AC012313.2-MUM1 in the LumA, AC026471.4-PLK5 in the LumB, AC027307.2-OAZ1 in the Basal-like and AC022431.1-HCN2 in the Her2 subtypes. Finally, our results highlighted target genes of CNA-driven enhancers and enhancer-related lncRNA-mRNA pairs could act as prognostic markers and potential therapeutic targets in breast cancer subtypes.
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