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Indirubin is a bisindole compound for the treatment of chronic myelocytic leukemia. Here, we presented a structure-guided method to improve the activity of a flavin-containing monooxygenase (bFMO) for the efficient production of indirubin in Escherichia coli. A flexible loop interlocked with the active pocket through a helix and the substrate tunnel rather than the active pocket in bFMO were identified to be two reconfigurable structures to improve its activity, resulting in K223R and N291T mutants with enhanced catalytic activity by 2.5- and 2.0-fold, respectively. A combined modification at the two regions (K223R/D317S) achieved a 6.6-fold improvement in catalytic efficiency (kcat/Km) due to enhancing π–π stacking interactions stabilization. Finally, an engineered E. coli strain was constructed by metabolic engineering, which could produce 860.7 mg/L (18 mg/L/h) indirubin, the highest yield ever reported. This work provides new insight into the redesign of FMOs to boost their activities and an efficient approach to produce indirubin. [ABSTRACT FROM AUTHOR]

The wick is the most crucial element of loop heat pipes (LHPs). At present, wick materials are limited to copper, stainless steel, nickel, and so on. Little research has been carried out on new wick materials. This paper reports the fabrication of aluminum wicks and performance tests of LHPs using aluminum wicks. Experimental data show that this LHP is capable of transferring a heating load of 130 W, while the thermal resistance is only approximately 0.04 K/W. Then, the experimental data were compared with those for LHPs using a polytetrafluoroethylene (PTFE) wick. Based on the SIMPLE algorithm, a 2-D unsteady-state heat transfer model and a 2-D steady-state flow model of the wicks are established to analyze the effects of wick material, pore size and porosity on the performance of the evaporator. The experimental data for LHPs with PTFE wicks are from the literature. The simulation results show that a PTFE wick can effectively reduce heat leakage, while an aluminum wick has better temperature uniformity and a lower casing temperature. However, wicks with large porosities have lower flow resistance. [ABSTRACT FROM AUTHOR]

By using the coupling method and the localization technique, we establish non-uniform gradient estimates for Markov semigroups of diffusions or stochastic differential equations driven by pure jump Lévy noises, where the coefficients only satisfy local monotonicity conditions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical outcomes of reconstruction of maxillary class III defect using 3D-printed titanium mesh. Methods: Twelve patients with maxillary class III defect from April 2015 to December 2016 were retrospectively studied. A 3D individualized maxillary stereo model based on mirror images of the unaffected maxilla was obtained to fabricate an anatomically adapted titanium mesh using computer-assisted design and manufacture. The individual titanium mesh was inserted into the maxillary class III defect after total maxillectomy. The incidence of postoperative complications was evaluated. The postoperative orbital volume and protrusion degree of eye were measured. Results: All patients were satisfied with their postoperative facial symmetry, without developing diplopia or endophthalmos. The postoperative orbital volumes were 26.41 ± 0.52 mL on the affected side and 26.55 ± 0.45 mL on the unaffected side. The postoperative protrusion degrees of affected and unaffected eyes were 16.21 ± 0.48 and 16.82 ± 0.79 mm, respectively. Titanium mesh exposure was observed in 2 patients and mild limitation of mouth opening was observed in 4 patients who underwent postoperative radiotherapy. Conclusion: Reconstruction of maxillary class III defect with 3D-printed titanium mesh can achieve successful clinical outcomes, which recovered orbital volume and protrusion degree of eye. [ABSTRACT FROM AUTHOR]

Chemical modifications on DNA molecules, such as 5-methylcytosine and 5-hydroxymethylcytosine, play important roles in the mammalian brain. A novel DNA adenine modification, N(6)-methyladenine (6mA), has recently been found in mammalian cells. However, the presence and function(s) of 6mA in the mammalian brain remain unclear. Here we demonstrate 6mA dynamics in the mouse brain in response to environmental stress. We find that overall 6mA levels are significantly elevated upon stress. Genome-wide 6mA and transcriptome profiling reveal an inverse association between 6mA dynamic changes and a set of upregulated neuronal genes or downregulated LINE transposon expression. Genes bearing stress-induced 6mA changes significantly overlap with loci associated with neuropsychiatric disorders. These results suggest an epigenetic role for 6mA in the mammalian brain as well as its potential involvement in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

N-α-acetyltransferase D (NatD) mediates N-α-terminal acetylation (Nt-acetylation) of histone H4 known to be involved in cell growth. Here we report that NatD promotes the migratory and invasive capabilities of lung cancer cells in vitro and in vivo. Depletion of NatD suppresses the epithelial-to-mesenchymal transition (EMT) of lung cancer cells by directly repressing the expression of transcription factor Slug, a key regulator of EMT. We found that Nt-acetylation of histone H4 antagonizes histone H4 serine 1 phosphorylation (H4S1ph), and that downregulation of Nt-acetylation of histone H4 facilitates CK2α binding to histone H4 in lung cancer cells, resulting in increased H4S1ph and epigenetic reprogramming to suppress Slug transcription to inhibit EMT. Importantly, NatD is commonly upregulated in primary human lung cancer tissues where its expression level correlates with Slug expression, enhanced invasiveness, and poor clinical outcomes. These findings indicate that NatD is a crucial epigenetic modulator of cell invasion during lung cancer progression. [ABSTRACT FROM AUTHOR]

Randomized, controlled trials (RCTs) have assessed the effect of colchicine therapy in prevention of pericardial effusion (PE) and atrial fibrillation (AF). However, the effects are still inconclusive. PubMed, Cochrane Library, Google Scholar, and EMBASE database were searched. Primary outcome was the risk of PE and AF. Ten RCTs with 1981 patients and a mean follow-up of 12.6 months were included. Colchicine therapy was not associated with a significantly lower risk of post-operative PE (RR, 0.89; 95 % CI 0.70-1.13; p = 0.33, I (2) = 72.8 %) and AF (RR, 0.77; 95 % CI 0.52-1.13; p = 0.18, I (2) = 47.3 %). However, rates of pericarditis recurrence, symptoms persistence, and pericarditis-related hospitalization were significantly decreased with colchicine treatment. In addition, cardiac tamponade occurrence was similar between groups, and adverse events were significantly higher in the colchicine group. Colchicine may not significantly decrease the post-operative risk of PE and AF. However, only limited studies about patients undergoing cardiac surgery provide data about PE and AF. [ABSTRACT FROM AUTHOR]

Graceful labelling is studied on undirected graphs since graceful graphs can be used in some H-decomposition problems. In this note, we investigate the directed graceful problem for many orientations of undirected trees with short diameters, and provide some directed trees that deny any digraceful labelling. [ABSTRACT FROM AUTHOR]

Some structures of spanning trees with many or less leaves in a connected graph are determined. We show (1) a connected graph G has a spanning tree T with minimum leaves such that T contains a longest path, and (2) a connected graph G on n vertices contains a spanning tree T with the maximum leaves such that Δ( G) = Δ( T) and the number of leaves of T is not greater than n − D( G) + 1, where D( G) is the diameter of G. [ABSTRACT FROM AUTHOR]

AbstractAim:YCP, a novel (1,4)-α-D-glucan, was isolated from the mycelium of the marine filamentous fungus Phoma herbarum YS4108. In this work, we investigated a YCP-binding cellular receptor expressed by macrophages and the intracellular signal transduction pathways involved in YCP-induced macrophage activation.Methods:Fluorescence-labeled YCP (fl-YCP) was prepared using the CDAP-activation method. Fluorescence confocal laser microscopy and fluorescence-activated cell sorting (FACS) were used to analyze the effect of fl-YCP on macrophages. To characterize the properties of the YCP receptor, carbohydrates and antibodies were used to inhibit the binding of fl-YCP to macrophages. Moreover, we investigated the role of membrane receptors Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), Toll-like receptor 6 (TLR6) and complement receptor 3 (CR3). We also examined the role of the p38 kinase pathway in mediating nitric oxide (NO) production.Results:YCP had an in vitro stimulatory effect on the release of NO in macrophage, and fl-YCP can bind directly to receptors on the surface of macrophages in a time- and dose-dependent manner. Competition studies show that LPS, laminarin, anti-TLR4 antibody and anti-CD11b (CR3) antibody could inhibit fl-YCP binding to macrophages. Conversely, mannose, anti-TLR2 and anti-TLR6 antibody could not. Treatment of RAW264.7 cells with YCP resulted in significant activation of p38 in a time-dependent manner. The specific p38 inhibitor SB203580 abrogated YCP-induced NO generation. Treatment of RAW264.7 cells with anti-TLR4 antibody and anti-CR3 antibody significantly reduced YCP-induced NO production and p38 activation.Conclusion:We have demonstrated that YCP-induced NO production occurs through the TLR4 and CR3 membrane receptors in a p38 kinase-dependent manner in macrophages.Acta Pharmacologica Sinica (2009) 30: 1008–1014; doi: 10.1038/aps.2009.93 [ABSTRACT FROM AUTHOR]

AbstractAim:Tumor immunotherapy aims at activating the body's own immune system to fight an existing tumor. Effective antitumor responses require tumor antigens to be presented to lymphocytes. We aimed to test the hypothesis that intratumoral administration of recombinant adenovirus encoding MIP3β would induce antitumor immunity by attracting and facilitating the interaction between lymphocytes and dendritic cells.Methods:A recombinant adenovirus encoding microphage inflammatory protein 3β (AdMIP3β) was constructed. The antitumor activity of AdMIP3β in BALB/c and C57BL/6 mice bearing CT26 colon adenocarcinoma and Lewis lung cancer was evaluated.Results:Immunotherapy with AdMIP3β resulted in significant inhibition of tumor growth and prolonged survival of tumor-bearing mice. Tumor-specific immune responses elicited by AdMIP3β include MHC class I-dependent CD8+ CTL-mediated immune response and IFN-γ response. Immunohistochemical staining demonstrated numerous CD11c+ cells and CD3+ T lymphocytes within tumor tissues of AdMIP3β-treated mice. These findings suggest that the mechanism of specific antitumor immunity induced by AdMIP3β may be involved in the chemoattraction of both T lymphocytes and DCs to the tumor site and thus facilitate the process of antigen capture and mature DC to prime naive T cells.Conclusion:The present study may be important in the exploration of the potential application of AdMIP3β in the treatment of a broad spectrum of tumors.Acta Pharmacologica Sinica (2009) 30: 355–363; doi: 10.1038/aps.2009.4 [ABSTRACT FROM AUTHOR]

The induction of active cellular responses against EGFR should be a promising approach for the treatment of those receptor-positive tumors. However, the immunity against EGFR is presumably difficult to elicit by vaccine based on self or syngeneic EGFR due to the immune tolerance acquired during the development in immune system. We proposed a model to break immune tolerance against self-EGFR through an altered immunogen source based on xenogeneic homologous EGFR. We have previously shown human EGFR as a xenoantigen could induce specific immune responses in mouse and cross-react with mouse EGFR, and resulted in therapeutic benefits for EGFR-positive mouse tumor. Here, we show a recombinant form of extracellular domain of mouse EGFR, in the presence of DCs, could activate human peripheral T cells to proliferate, secret IFN-γ, the induced responses could cross-react with human EGFR and kill autologous EGFR-positive lung cancer cells which could be blocked by anti-CD8 and anti-MHC class I antibody. There is no detectable cytotoxical activity against lung tissue, liver tissue and kidney tissue derived from paracancerous normal tissue. These observations suggest that antitumor immunity induced by the truncated mouse EGFR may be provoked in a cross-reaction between mouse EGFR and self-EGFR, and may provide insight into treatment of EGFR-positive tumors through induction of the autoimmune responses against EGFR. [ABSTRACT FROM AUTHOR]

Based on the questionnaire investigation, the authors make a comparative study on local residents’ perception of tourism impacts in Xidi, Zhouzhaung and Jiuhua Mountain. The result shows that residents of the three places tend to have strong and consistent perception of its positive economic, socio-cultural and environmental impacts, but distinctly diverse ones of its negative impacts. Residents in Xidi and Zhouzhuang also have noticeable perception of its negative environmental impacts while those in Jiuhua Mountain have weaker perception of them. The research confirms the fact that residents are more liable to have positive perceptions at the early stage of the life cycle of the tourist places. The authors conclude that there exists a nonlinear relationship between residents’ perception and tourism development stages, and that tourism socio-cultural impact may appear at an early stage of tourism development instead of being no universal. [ABSTRACT FROM AUTHOR]

The article examines the nucleotide sequence of a complementary DNA encoding myosin VI head domain, which was isolated within the mantle of the Zhikong scallop Chlamys farreri. Myosins are molecular motors that utilize the energy of adenosine triphosphate, the fourth class of myosins that has the capability to move processively towards the end of actin filaments. Reverse transcriptase polymerase chain reaction was used to analyze the tissue expression of Zhikong scallop. Ribonucleic acid was also extracted from the different parts of the scallop wherein the aliquots of the total RNA was reverse.