What Differs on the Enzymatic Acetylation Mechanisms for Arylamines and Arylhydrazines Substrates? A Theoretical Study

The acetylation mechanisms of several selected typical substrates from experiments, including arylamines and arylhydrazines, are investigated with the density functional theory in this paper. The results indicate that all the transition states are characterized by a four-membered ring structure, and hydralazine (HDZ) is the most potent substrate. The bioactivity for all the compounds is increased in a sequence of PABA ≈ 4-AS < 4-MA < 5-AS ≈ INH < HDZ. The conjunction effect and the delocalization of the lone pairs of N atom play a key role in the reaction. All the results are consistent with the experimental data

Curcumin Induces p53-Null Hepatoma Cell Line Hep3B Apoptosis through the AKT-PTEN-FOXO4 Pathway

Objective. Curcumin (diferuloylmethane) is a yellow-colored polyphenol with antiproliferative and proapoptotic activities to various types of cancer cells. This study explored the mechanism by which curcumin induces p53-null hepatoma cell apoptosis. Results. AKT, FOXO1, and FOXO3 proteins were downregulated after curcumin treatment. Conversely, PTEN was upregulated. Subcellular fractionations revealed that the FOXO4 protein translocated from cytosol into the nucleus after curcumin treatment. Overexpression of FOXO4 increases the sensitivity of Hep3B cells to curcumin. Knockdown of the FOXO4 gene by siRNA inhibits the proapoptotic effects of curcumin on Hep3B cell. Conclusions. This study revealed the AKT/PTEN/FOXO4 pathway as a potential candidate of target for treatment of p53-null liver cancers

Regression of mouse-derived renal cancer by adoptive transfer of tumor-reactive RNAi-induced TGF-beta-insensitive CD8+ T cells

Transforming growth factor beta (TGF-beta) is a potent immunosuppressant. The present study was conducted to develop a treatment strategy through adoptive transfer of tumor-reactive RNAi-induced TGF-beta-insensitive CD8+ T cells. BALB/c mice were primed with irradiated Renca cells. CD8+ T cells were isolated from the spleen of primed animals, expanded ex vivo and were rendered TGF-beta-insensitive by infecting with a retrovirus containing shRNA to mouse TGF-beta type II receptor gene (MSCV-shRNA-T). Control CD8+ T cells consist of those infected with retroviruses containing shRNA to non specific gene (MSCV-shRNA-N) and naive CD8+ T cells. The effect of all groups of CD8+ T cells on Renca cells were analyzed by semi-quantitative RT-PCR, Western-blot, in vitro and in vivo assay. MSCVshRNA-T group of CD8+ T cells were resistant to the antiproliferative effect of exogenous TGF-beta, while control groups were not. Results of Western blot showed the Smad pathway was disrupted in MSCV-shRNA-T group, which confirmed the blockade of the signal transduction pathway. In vitro cytotoxic assay revealed that these tumor-reactive, TGF-beta-insensitive CD8+ T cells killed Renca cells specifically and strongly. Adoptive transfer of these MSCV-shRNA-T CD8+ T cells to BALB/c tumorbearing mice showed strong tumor-specific cytotoxic T lymphocyte responses and antitumor immunity against Renca renal cancer. Based on these results, we predict that adoptive transfer of tumor-reactive RNAi-induced TGF-beta-insensitive CD8+ T cells may be effective to renal cancer therapy.Keywords: Transforming growth factor beta, adoptive transfer, RNA interference, renal cancer, renca cells, immunotherapyAfrican Journal of Biotechnology Vol. 9(33), pp. 5274-5283, 16 August, 201

Electronic band structures of Ge1−xSnx semiconductors: A first-principles density functional theory study

[[abstract]]We conduct first-principles total-energy density functional calculations to study the band structures in Ge 1− x Sn x infrared semiconductor alloys. The norm-conserving optimized pseudopotentials of Ge and Sn have been constructed for electronic structure calculations. The composition-bandgap relationships in Ge 1−x Sn x lattices are evaluated by a detailed comparison of structural models and their electronic band structures. The critical Sn composition related to the transition from indirect- to direct-gap in Ge 1−x Sn x alloys is estimated to be as low as x∼ 0.016 determined from the parametric fit. Our results show that the crossover Sn concentration occurs at a lower critical Sn concentration than the values predicted from the absorption measurements. However, early results indicate that the reliability of the critical Sn concentration from such measurements is hard to establish, since the indirect gap absorption is much weaker than the direct gap absorption. We find that the direct band gap decreases exponentially with the Sn composition over the range 0 0.375, in very good agreement with the theoretical observed behavior [D. W. Jenkins and J. D. Dow, Phys. Rev. B 36, 7994, 1987]. For homonuclear and heteronuclear complexes of Ge 1−x Sn x alloys, the indirect band gap at L-pointis is found to decrease homonuclear Ge-Ge bonds or increase homonuclear Sn-Sn bonds as a result of the reduced L valley. All findings agree with previously reported experimental and theoretical results. The analysis suggests that the top of valence band exhibits the localization of bond charge and the bottom of the conduction band is composed of the Ge 4s4p and/or Sn 5s5p atomic orbits.[[booktype]]紙本[[booktype]]電子

Wearable sensor-based human activity recognition using hybrid deep learning techniques

Human activity recognition (HAR) can be exploited to great benefits in many applications, including elder care, health care, rehabilitation, entertainment, and monitoring. Many existing techniques, such as deep learning, have been developed for specific activity recognition, but little for the recognition of the transitions between activities. This work proposes a deep learning based scheme that can recognize both specific activities and the transitions between two different activities of short duration and low frequency for health care applications. In this work, we first build a deep convolutional neural network (CNN) for extracting features from the data collected by sensors. Then, the long short-term memory (LTSM) network is used to capture long-term dependencies between two actions to further improve the HAR identification rate. By combing CNN and LSTM, a wearable sensor based model is proposed that can accurately recognize activities and their transitions. The experimental results show that the proposed approach can help improve the recognition rate up to 95.87% and the recognition rate for transitions higher than 80%, which are better than those of most existing similar models over the open HAPT dataset

FOXO/Fringe is necessary for maintenance of the germline stem cell niche in response to insulin insufficiency

AbstractThe stem cell niche houses and regulates stem cells by providing both physical contact and local factors that regulate stem cell identity. The stem cell niche also plays a role in integrating niche-local and systemic signals, thereby ensuring that the balance of stem cells meets the needs of the organism. However, it is not clear how these signals are merged within the niche. Nutrient-sensing insulin/FOXO signaling has been previously shown to directly control Notch activation in the Drosophila female germline stem cell (GSC) niche, which maintains the niche and GSC identity. Here, we demonstrate that FOXO directly activates transcription of fringe, a gene encoding a glycosyltransferase that modulates Notch glycosylation. Fringe facilitates Notch inactivation in the GSC niche when insulin signaling is low. We also show that the Notch ligand predominantly involved is GSC niche-derived Delta. These results reveal that FOXO-mediated regulation of fringe links the insulin and Notch signaling pathways in the GSC niche in response to nutrition, and emphasize that stem cells are regulated by complex interactions between niche-local and systemic signals

The Phytochemical Shikonin Stimulates Epithelial-Mesenchymal Transition (EMT) in Skin Wound Healing

Although various pharmacological activities of the shikonins have been documented, understanding the hierarchical regulation of these diverse bioactivities at the genome level is unsubstantiated. In this study, through cross examination between transcriptome and microRNA array analyses, we predicted that topical treatment of shikonin in vivo affects epithelial-mesenchymal transition (EMT) and the expression of related microRNAs, including 200a, 200b, 200c, 141, 205, and 429 microRNAs, in mouse skin tissues. In situ immunohistological analyses further demonstrated that specific EMT regulatory molecules are enhanced in shikonin-treated epidermal tissues. RT-PCR analyses subsequently confirmed that shikonin treatment downregulated expression of microRNA-205 and other members of the 200 family microRNAs. Further, expression of two RNA targets of the 200 family microRNAs in EMT regulation, Sip1 (Zeb2) and Tcf8 (Zeb1), was consistently upregulated by shikonin treatment. Enhancement of these EMT activities was also detected in shikonin-treated wounds, which repaired faster than controls. These results suggest that topical treatment with shikonin can confer a potent stimulatory effect on EMT and suppress the expression of the associated microRNAs in skin wound healing. Collectively, these cellular and molecular data provide further evidence in support of our previous findings on the specific pharmacological effects of shikonin in wound healing and immune modulation