Experiments, molecular dynamics simulations, and quantum chemistry calculations on the effect of gemini surfactants' headgroup on the oil-water interfacial tension.

The effect of the Gemini surfactant headgroup on the oil-water interfacial tension has yet to be systematically revealed. In this work, anionic Gemini surfactants with different hydrophilic headgroups (carboxylic, sulfuric, and sulfonic) were designed and synthesized. The oil-water interfacial tension was tested. The essential parameters for evaluating the interface characteristics, including the oil-water interfacial layer thickness, the coordination number, and the diffusion coefficient, were calculated employing molecular dynamics simulation. The surface electrostatic potential explained the quantitative mechanism of the hydrophobicity and lipophilicity of three types of Gemini surfactants through quantum chemical calculations. The oil-water interfacial tension difference of the Gemini surfactants was revealed at the electronic level. This paper will provide theoretical guidance for designing Gemini surfactants with a high-efficiency performance to enhance oil recovery.

ROS1-mediated decrease in DNA methylation and increase in expression of defense genes and stress response genes in Arabidopsis thaliana due to abiotic stresses.

BACKGROUND: Small interfering RNAs (siRNAs) target homologous genomic DNA sequences for cytosine methylation, known as RNA-directed DNA methylation (RdDM), plays an important role in transposon control and regulation of gene expression in plants. Repressor of silencing 1 (ROS1) can negatively regulate the RdDM pathway. RESULTS: In this paper, we investigated the molecular mechanisms by which an upstream regulator ACD6 in the salicylic acid (SA) defense pathway, an ABA pathway-related gene ACO3, and GSTF14, an endogenous gene of the glutathione S-transferase superfamily, were induced by various abiotic stresses. The results demonstrated that abiotic stresses, including water deficit, cold, and salt stresses, induced demethylation of the repeats in the promoters of ACD6, ACO3, and GSTF14 and transcriptionally activated their expression. Furthermore, our results revealed that ROS1-mediated DNA demethylation plays an important role in the process of transcriptional activation of ACD6 and GSTF14 when Arabidopsis plants are subjected to cold stress. CONCLUSIONS: This study revealed that ROS1 plays an important role in the molecular mechanisms associated with genes involved in defense pathways in response to abiotic stresses.

Potential roles of N6-methyladenosine (m6A) in immune cells.

N6-methyl-adenosine (m6A) is one of the most common internal modifications on RNA molecules present in mammalian cells. Deregulation of m6A modification has been recently implicated in many types of human diseases. Therefore, m6A modification has become a research hotspot for its potential therapeutic applications in the treatment of various diseases. The immune system mostly involves different types of immune cells to provide the first line of defense against infections. The immunoregulatory network that orchestrate the immune responses to new pathogens plays a pivotal role in the development of the disease. And m6A modification has been demonstrated to be a major post-transcriptional regulator of immune responses in cells. In this review, we summarize the participants involved in m6A regulation and try to reveal how m6A modification affects the immune responses via changing the immunoregulatory networks.

C-undecylcalix[4]resorcinarene Langmuir-Blodgett/Porous Reduced Graphene Oxide Composite Film as a Electrochemical Sensor for the Determination of Tryptophan.

In this study, a composite film was developed for the electrochemical sensing of tryptophan (Trp). Porous reduced graphene oxide (PrGO) was utilized as the electron transfer layer, and a C-undecylcalix[4]resorcinarene Langmuir-Blodgett (CUCR-LB) film served as the molecular recognition layer. Atomic force microscopy (AFM), transmission electron microscopy (TEM), Raman spectroscopy, scanning electron microscopy (SEM), and electrochemical experiments were employed to analyze the characteristics of the CUCR-LB/PrGO composite film. The electrochemical behavior of Trp on the CUCR-LB/PrGO composite film was investigated, revealing a Trp linear response range of 1.0 × 10-7 to 3.0 × 10-5 mol L-1 and a detection limit of 3.0 × 10-8 mol L-1. Furthermore, the developed electroanalytical method successfully determined Trp content in an amino acid injection sample. This study not only introduces a rapid and reliable electrochemical method for the determination of Trp but also presents a new strategy for constructing high-performance electrochemical sensing platforms.

The viral suppressor HCPro decreases DNA methylation and activates auxin biosynthesis genes.

Auxin has profound effects on plant growth and development. In addition to participating in plant growth and development, the auxin signaling pathway is involved in plant defense against pathogens. In this study, we investigated the molecular mechanism by which helper-component protease (HCPro) encoded by the Tobacco vein banding mosaic virus (TVBMV) activates auxin biosynthesis genes (YUCs) and interferes with the auxin signaling pathway. Our results demonstrated that the viral suppressor HCPro decreased the DNA methylation of dispersed repeats (DRs) within the promoters of YUC1, YUC5 and YUC10 and transcriptional activated these YUC genes targeted by RNA-directed DNA methylation (RdDM), leading to an increase in auxin accumulation in plants. Furthermore, we found that the induction of these YUCs by HCPro was attenuated in ros1 mutant plants, suggesting that HCPro-mediated transcriptional activation of the genes was partly dependent on ROS1-mediated DNA demethylation.

Development of an autophagy-related signature in pancreatic adenocarcinoma.

In recent years, autophagy has become a research hotspot in the field of pancreatic adenocarcinoma (PAAD) due to its ambiguous roles in pancreatic tumor progression. Hence, it is necessary to assess its clinical significance in a larger cohort of patients with PAAD. Here, we identified autophagy-related genes with prognostic value in PAAD and constructed a risk model based on these genes. We found that patients in high-risk group were significantly associated with poor prognosis. Genome mutation analysis suggested that KRAS and TP53 mutations were significantly higher in high-risk groups. In addition, functional enrichment analysis showed that high-risk groups were associated with immune cell infiltration and tumor-associated signaling pathways. We further performed CIBERSORT analysis and observed increased macrophage infiltration in high-risk group, but decreased B and T cell counts compared to that in low-risk group. Gene set enrichment analysis indicated that the Hippo pathway was enriched in the high-risk group. Further, using weighted gene co-expression network analysis, Yes-associated protein 1 (YAP1) was identified as a critical hub gene. Interestingly, we found that the autophagy status and YAP1 expression status could influence each other, thus creating a positive feedback loop. In conclusion, in this study, we highlighted the clinical significance of autophagy in pancreatic cancer, constructed an autophagy-related prognostic predictive system, and identified a promising target for autophagy regulation in pancreatic cancer.

Metformin targets a YAP1-TEAD4 complex via AMPKα to regulate CCNE1/2 in bladder cancer cells.

BACKGROUND: Metformin has been reported to function as the anti-tumor inhibiting the growth of different types of cancers, including bladder cancer. But there are few reports on the roles of Yap1, the key molecule of Hippo pathway, in the metformin induced inhibition of bladder cancer (BLCA). We are wondering if the inhibitory effect of metformin on bladder cancer is fulfilled via Yap1 and exploring the related mechanism. METHODS: MTS and colony formation assays were used to explore the cellular viabilities and proliferation of BLCA cells challenged by metformin at different concentrations, in vitro. Flow Cytometry (FCM) was used to analyze the cell cycle and the cellular apoptosis of the BLCA cells. Western Blot was performed to detect the expressions of AMPKα, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines. RNAi method was used for the related genetic functional analysis. The relationships among Yap1, TEADs and CCNE1/2 were predicted and evaluated using bioinformatics, dual-luciferase reporter and co-immunoprecipitation (Co-IP) assays. For in vivo experiments, a xenograft model was used to investigate the effects of metformin on the proliferation of BLCA cells. And Immunohistochemistry (IHC) assay was performed to assess the expressions of CCNE1/2 and Yap1 proteins in the tumor tissues from the model. RESULTS: Metformin could inhibit the proliferation of the BLCA cells via inducing the G1 cell cycle arrest without apoptosis. And metformin upregulated the phosphorylated AMPKα and decreased the expressions of Yap1 and CCND1, CCNE1/2 and CDK4/6. AMPK inhibition by compound C (CC) restored the cell proliferation and the G1 cell cycle arrest induced by metformin, in vivo. Knockdown of YAP1 inhibited the proliferation of BLCA cells and caused the cell cycle arrest at G1 phase by decreasing the expressions of CCNE1/2 and other G1 phase related molecules, which has been restored by the Yap 5SA mutant. Bioinformatics analysis showed that trans-factor TEAD4 was highly expressed and positively associated with the expressions of CCNE1 and CCNE2 in BLCA and only TEAD4 was precipitated by Yap1 in the BLCA cells. Further studies demonstrated that Yap1 positively regulated both CCNE1 and CCNE2 expressions via forming complex with TEAD4. Furthermore, we observed that metformin inhibited the cell proliferation by decreasing the expressions of Yap1 and both CCNE1 and CCNE2 in xenograft model. CONCLUSIONS: The results of our study reveal a new potential regulatory pathway in which metformin inhibits cell proliferation via AMPKα/Yap1/TEAD4/CCNE1/2 axis in BLCA cells, providing new insights into novel molecular therapeutic targets for BLCA.

3D Graphene-Nitrogen Doped Carbon Nanotubes Network Modified Electrode as Sensing Materials for the Determination of Urapidil.

In this work, a three dimensional (3D) graphene-nitrogen doped carbon nanotubes (G-NCNTs) network was successfully fabricated on the surface of a glassy carbon (GC) electrode using the pulse potential method (PPM) in a graphene oxide-nitrogen doped carbon nanotubes (GO-NCNTs) dispersion. The morphological and characteristics of GO-NCNTs and G-NCNTs nanocomposites were investigated by atomic force microscopy (AFM), scanning electron microscopy (SEM), UV-vis spectroscopy, Raman spectroscopy, and electrochemical experiments. The 3DG-NCNTs network was applied as a new voltammetric material for the fabrication of an electrochemical platform for determination of urapidil. Systematic electrochemical tests demonstrate that the 3DG-NCNTs network modified GC electrode can effectively increase the response to the oxidation of urapidil. Under the optimum conditions, the electrochemical response was linear with urapidil concentrations in the range of 1.0 × 10-8~2.0 × 10-6 mol·L-1, while a low detection limit of 5.0 × 10-9 mol·L-1 was obtained for urapidil. Moreover, the proposed sensing platform exhibited good results for sensitivity, reproducibility, selectivity, and stability, which makes it very suitable for use as an ideal inexpensive and rapid analytical method applicable for complex drug matrices.

Dipeptidyl peptidase-4 inhibitor, vildagliptin, inhibits pancreatic beta cell apoptosis in association with its effects suppressing endoplasmic reticulum stress in db/db mice.

AIMS: Vildagliptin promotes beta cell survival by inhibiting cell apoptosis. It has been suggested that chronic ER (endoplasmic reticulum) stress triggers beta cell apoptosis. The objective of the study is to explore whether the pro-survival effect of vildagliptin is associated with attenuation of endoplasmic reticulum stress in islets of db/db mice. METHODS: Vildagliptin was orally administered to db/db mice for 6 weeks, followed by evaluation of beta cell apoptosis by caspase3 activity and TUNEL staining method. Endoplasmic reticulum stress markers were determined with quantitative RT-PCR, immunohistochemistry and immunoblot analysis. RESULTS: After 6 weeks of treatment, vildagliptin treatment increased plasma active GLP-1 levels (22.63±1.19 vs. 11.69±0.44, P<0.001), inhibited beta cell apoptosis as demonstrated by lower amounts of TUNEL staining nuclei (0.37±0.03 vs. 0.55±0.03, P<0.01) as well as decreased caspase3 activity (1.48±0.11 vs. 2.67±0.13, P<0.01) in islets of diabetic mice compared with untreated diabetic group. Further, vildagliptin treatment down-regulated several genes related to endoplasmic reticulum stress including TRIB3 (tribbles homolog 3) (15.9±0.4 vs. 33.3±1.7, ×10⁻³, P<0.001), ATF-4(activating transcription factor 4) (0.83±0.06 vs. 1.42±0.02, P<0.001) and CHOP(C/EBP homologous protein) (0.07±0.01 vs. 0.16±0.01, P<0.001). CONCLUSIONS: Vildagliptin promoted beta cell survival in db/db mice in association with down-regulating markers of endoplasmic reticulum stress including TRIB3, ATF-4 as well as CHOP.