Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA) is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA-10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD). We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed

Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects

Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex-drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches

Knowledge-Enriched Visual Storytelling

Stories are diverse and highly personalized, resulting in a large possible output space for story generation. Existing end-to-end approaches produce monotonous stories because they are limited to the vocabulary and knowledge in a single training dataset. This paper introduces KG-Story, a three-stage framework that allows the story generation model to take advantage of external Knowledge Graphs to produce interesting stories. KG-Story distills a set of representative words from the input prompts, enriches the word set by using external knowledge graphs, and finally generates stories based on the enriched word set. This distill-enrich-generate framework allows the use of external resources not only for the enrichment phase, but also for the distillation and generation phases. In this paper, we show the superiority of KG-Story for visual storytelling, where the input prompt is a sequence of five photos and the output is a short story. Per the human ranking evaluation, stories generated by KG-Story are on average ranked better than that of the state-of-the-art systems. Our code and output stories are available at https://github.com/zychen423/KE-VIST.Comment: AAAI 202

Determination of band alignment in the single layer MoS2/WSe2 heterojunction

The emergence of transition metal dichalcogenides (TMDs) as 2D electronic materials has stimulated proposals of novel electronic and photonic devices based on TMD heterostructures. Here we report the determination of band offsets in TMD heterostructures by using microbeam X-ray photoelectron spectroscopy ({\mu}-XPS) and scanning tunneling microscopy/spectroscopy (STM/S). We determine a type-II alignment between $\textrm{MoS}_2$ and $\textrm{WSe}_2$ with a valence band offset (VBO) value of 0.83 eV and a conduction band offset (CBO) of 0.76 eV. First-principles calculations show that in this heterostructure with dissimilar chalcogen atoms, the electronic structures of $\textrm{WSe}_2$ and $\textrm{MoS}_2$ are well retained in their respective layers due to a weak interlayer coupling. Moreover, a VBO of 0.94 eV is obtained from density functional theory (DFT), consistent with the experimental determination.Comment: ^ These authors contributed equally. *Corresponding author E-mail: [email protected], [email protected] 20 pages, 4 figures in main tex

Unraveling the Role of the rssC Gene of Serratia marcescens by Atomic Force Microscopy

100學年度研究獎補助論文[[abstract]]The product and direct role of the rssC gene of Serratia marcescens is unknown. For unraveling the role of the rssC gene, atomic force microscopy has been used to identify the surfaces of intact S. marcescens wild-type CH-1 cells and rssC mutant CH-1ΔC cells. The detailed surface topographies were directly visualized, and quantitative measurements of the physical properties of the membrane structures were provided. CH-1 and CH-1ΔC cells were observed before and after treatment with lysozyme, and their topography-related parameters, e.g., a valley-to-peak distance, mean height, surface roughness, and surface root-mean-square values, were defined and compared. The data obtained suggest that the cellular surface topography of mutant CH-1ΔC becomes rougher and more precipitous than that of wild-type CH-1 cells. Moreover, it was found that, compared with native wild-type CH-1, the cellular surface topography of lysozyme-treated CH-1 was not changed profoundly. The product of the rssC gene is thus predicted to be mainly responsible for fatty-acid biosynthesis of the S. marcescens outer membrane. This study represents the first direct observation of the structural changes in membranes of bacterial mutant cells and offers a new prospect for predicting gene expression in bacterial cells.[[journaltype]]國外[[incitationindex]]SCI[[booktype]]紙本[[countrycodes]]GB