Chemical Composition and Cytotoxic Activities of Petroleum Ether Fruit Extract of Fruits of Brucea javanica (Simarubaceae)

Purpose: To investigate the chemical composition and antitumor activity of the petroleum ether extract of the dried ripe fruits of Brucea javanica.Methods: The composition of petroleum ether extract was analyzed by gas chromatography/mass spectrometric (GC/MS) and their antitumor activities were determined by MTT assay.Results: GC/MS spectrometry results indicate that the petroleum ether extract was a mixture of esters, fatty acids, sterides, pregnanones, terpenes, alkaloids, alkenes, alcohols, ketones, aldehydes and other compounds. The results also revealed the significant antitumor activity of the extract with IC50 of 9.14, 12.45, 15.15, 16.13, 22.26, and 27.97 μg/mL against A549, CNE, MCF-7, NCI-H460, HepG2, and KB-3-1 cell lines, respectively.Conclusion: The study establishes the chemical composition and cytotoxic activity of the petroleum ether extract of the plant fruits. There is need for further investigations to isolate more potent compounds and structurally modify the known compounds to retain activity and lower toxicity and thus lead to the possible development of Brucea javanica oil.Keywords: Brucae javanica, Mass spectra, Cytotoxic activity, Anti-tumour

Exploiting Cognitive Structure for Adaptive Learning

Adaptive learning, also known as adaptive teaching, relies on learning path recommendation, which sequentially recommends personalized learning items (e.g., lectures, exercises) to satisfy the unique needs of each learner. Although it is well known that modeling the cognitive structure including knowledge level of learners and knowledge structure (e.g., the prerequisite relations) of learning items is important for learning path recommendation, existing methods for adaptive learning often separately focus on either knowledge levels of learners or knowledge structure of learning items. To fully exploit the multifaceted cognitive structure for learning path recommendation, we propose a Cognitive Structure Enhanced framework for Adaptive Learning, named CSEAL. By viewing path recommendation as a Markov Decision Process and applying an actor-critic algorithm, CSEAL can sequentially identify the right learning items to different learners. Specifically, we first utilize a recurrent neural network to trace the evolving knowledge levels of learners at each learning step. Then, we design a navigation algorithm on the knowledge structure to ensure the logicality of learning paths, which reduces the search space in the decision process. Finally, the actor-critic algorithm is used to determine what to learn next and whose parameters are dynamically updated along the learning path. Extensive experiments on real-world data demonstrate the effectiveness and robustness of CSEAL.Comment: Accepted by KDD 2019 Research Track. In Proceedings of the 25th ACM SIGKDD International Conference on Knowledge Discovery & Data Mining (KDD'19

Evaluation of Embryotoxicity of Radix scutellariae Based on Embryonic Stem Test

Purpose: To determine the potential embryotoxicity of Radix scutellariae (RS) extract using an embryonic stem cell test (EST) and to evaluate its effect on the differentiation of mouse embryonic stem (ES) cells.Methods: All the test samples were obtained by water extraction method. The embryotoxicity of RS was assessed with cytotoxicity assays, namely, embryonic stem (ES) cells (IC50ES) and 3T3 fibroblasts (IC503T3), as well as cardiac differentiation inhibition assay (ID50ES). The expression of specific genes and proteins was analyzed by quantitative reverse transcription – polymerase chain reaction (RT-PCR) and Western blot.Results: RS was weakly embryotoxic with IC50ES, IC503T3 and ID50ES of 0.1524, 0.1061, and 0.4169 mg/ml, respectively. Also RS had discordant effects on the expression of tissue-specific genes and proteins in three germ layers, promoting differentiation of the ectoderm (⋆p < 0.05; ⋆⋆p < 0.01) and endoderm (⋆p < 0.05; ⋆⋆p < 0.01; ⋆⋆⋆p < 0.001), while inhibiting mesoderm differentiation (⋆p < 0.05; ⋆⋆p < 0.01; ⋆⋆⋆p < 0.001). The effect of RS on the embryonic development of the three germ layers was concentration-dependent.Conclusion: These results indicate that RS possesses weak embryotoxicity. The variability in the effects of RS may be responsible for its weak embryotoxicity.Keywords: Embryonic stem test, Radix scutellariae, Embryotoxicity, Cardiac differentiation inhibition assay, Ectoderm, Endoderm, Mesoder

Optogenetically Controlled TrkA Activity Improves the Regenerative Capacity of Hair-Follicle-Derived Stem Cells to Differentiate into Neurons and Glia.

Hair-follicle-derived stem cells (HSCs) originating from the bulge region of the mouse vibrissa hair follicle are able to differentiate into neuronal and glial lineage cells. The tropomyosin receptor kinase A (TrkA) receptor that is expressed on these cells plays key roles in mediating the survival and differentiation of neural progenitors as well as in the regulation of the growth and regeneration of different neural systems. In this study, the OptoTrkA system is introduced, which is able to stimulate TrkA activity via blue-light illumination in HSCs. This allows to determine whether TrkA signaling is capable of influencing the proliferation, migration, and neural differentiation of these somatic stem cells. It is found that OptoTrkA is able to activate downstream molecules such as ERK and AKT with blue-light illumination, and subsequently able to terminate this kinase activity in the dark. HSCs with OptoTrkA activity show an increased ability for proliferation and migration and also exhibited accelerated neuronal and glial cell differentiation. These findings suggest that the precise control of TrkA activity using optogenetic tools is a viable strategy for the regeneration of neurons from HSCs, and also provides a novel insight into the clinical application of optogenetic tools in cell-transplantation therapy

Assessment of the Developmental Toxicity of Epidermal Growth Factor using Embryonic Stem Cell Test

Purpose: To determine whether epidermal growth factor (EGF) is involved in reproductive developmental toxicity, using the embryonic stem cell test (EST), as well as ascertain how EGF influences embryonic development.Methods: To predict developmental toxicity on the basis of reducing cell viability and inhibition of differentiation of embryonic stem cells, EST was used to assess changes in different blastodermic genes and expression of proteins including ectodermal-specific genes Pax6, NF-H and glial fibrillary acidic protein (GFAP), mesodermal-specific genes BMP4, GATA4, and MyoD, and endodermal-specific genes, viz, α-fetoprotein, transthyretin (TTR), and albumin, as well as undifferentiated genes, Nanog and Oct4.Results: The results indicate that EGF was weakly embryotoxic with IC50ESC (i.e., the concentration that reduced ESC viability by 50 %), IC503T3 (the concentration that reduced 3T3 cell viability by 50 %), and ID50ESC (the concentration that inhibited differentiation of ESC by 50 %) of 6.773, 10.531, and 1.793 μg/mL, respectively. The expression levels of tissue-specific genes of the three germ layers were mainly promoted by 0.01 - 1 μg/mL EGF. Distinctively, relatively high concentrations of EGF caused a discordant effect on the three germ layers. High concentrations of EGF promoted differentiation of the ectoderm and mesoderm, and either inhibited or had mostly no impact on the endoderm.Conclusion: The imbalance of the three layer-specific genes and expression of proteins, as a result of EGF, might be responsible for its weak level of developmental toxicity. The sensitivity of TTR means that further investigation is required to determine whether it can be used as an embryotoxicity biomarker for growth factors.Keywords: Embryonic stem cell test, Epidermal growth factor, Developmental toxicity, Germ layers, Blastodermic genes, Protein expressio

CuI catalyzed sulfonylation of organozinc reagents with sulfonyl halides

In this study, a facile CuI catalyzed synthesis of sulfones involving a nucleophilic addition of functionalized organozinc reagents to organic sulfonyl chlorides is realized. This reaction proceeds efficiently at room temperature, giving rise to various functional group substituted sulfones, generally in moderate to high yields. The method provides a novel, simple, and promising strategy for functionalized sulfone synthesis in the research field of sulfur chemistry