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Two new indole alkaloid derivatives ( 1, 2), together with six known indole alkaloids ( 3 - 8) were isolated from the 70% EtOH/H2O extract of the stem of Nauclea officinalis. Their structures were determined on the basis of extensive analyses of spectroscopic data ( IR, MS, 1D- and 2D-NMR). All the isolates were evaluated for their anti-inflammatory activities on lipopolysaccharide ( LPS)-induced nitric oxide ( NO) production in RAW 264.7, and all the compounds showed significant inhibitory activities with the IC50 values of 0.82, 6.45, 9.75, 1.34, 3.40, 2.69, 1.58, and 1.96 μ m, compared to the positive drug control group aminoguanidine with an IC50 value of 1.80 μ m, especially compound 1 had the most significant activity. [ABSTRACT FROM AUTHOR]

Background: In recent years, the T-cell therapy and immune checkpoint inhibitors toward CTLA-4 and PD-1/PD-L1 axis antibody therapy have acquired encouraging success. However, most of patients were still not benefited with lots of troubles, such as low penetration of tissues/cells, strong immunogenicity and cytokine release syndrome, and long manufacturing process and expensive costs. By contrast, the immune-modulating small molecules possessed natural advantages to overcome these obstacles and might achieve greater success.Purpose: Exploring the potent immune-modulating natural small molecules and revealing what kinds of molecules or structures with the immunomodulatory activity against cancers.Methods: A novel non-cytotoxic T-cell immunomodulating screening model was used to identify the cytotoxic/selective/immunomodulatory bioactivity for 148 natural steroidal saponins. The structure-activity relationships (SARs) research was used to reveal the key groups for immunomodulation/cytotoxicity/selectivity. The negative selection was used to isolate and purify the T-cell. The cell viability assay was used to measure the anti-cancer effect in vitro. The ELISA assay was used to detect the cytokines for IL-1β, IL-6, TNF-α, IFN-γ, IL-12, perforin and granzyme B (GZMB). The western blotting assay was used to research the immunomodulatory mechanism. The siRNA knockdown was used to generate the IFN-γ resistant melanoma cells. The NOG immune-deficient mice were used to evaluate the anti-tumor efficacy in vivo. The peripheral blood samples from 10 cancer patients were used to detect the broad population anti-tumor efficacy.Results: It was reported that the correlation among structures and immunomodulation/ cytotoxicity/selectivity, in which opening ring-F with 26-O-glucopyranosyl, disaccharide and trisaccharide chains at C-3, steric hindrance and polarity of C-22 were key immunomodulatory groups. Moreover, taccaoside A was identified as the most potent candidate against cancer cells, including non-small cell lung cancer, triple negative breast cancer, and the IFN-γ resistant melanoma, partly through enhancing T lymphocyte mTORC1-Blimp-1 signal to secrete GZMB. Besides, 10 patients derived T-cell also would be modulated against cancer cells in vitro. Moreover, the overall survival was great extended (>140 days vs 93 days) with nearly 100% tumor burden disappearance (0 mm3vs 1006 ± 79.5 mm3) in mice.Conclusion: This work demonstrated one possibility for this concerned purpose, and identified a potent immune-modulating natural molecule taccaoside A, which might contribute to cancer immunotherapy in future. [ABSTRACT FROM AUTHOR]

Objective Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown. Design Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and proinflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays. Results Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis. Conclusions This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis. [ABSTRACT FROM AUTHOR]

对通信网络中通道的带宽发生变化是否会影响通道的最大通信能力的问题, 提出最大流的 弧容忍度问题。结合最大流与最小截的性质, 将最小截内外的弧分别进行考虑, 提出了求解每条弧的弧容 忍度的多项式时间算法, 并对算法进行分析比较。实例结果表明, 算法复杂度低, 易于操作。. For the problem that whether the change of channel's bandwidth will influence the maximum communication ability in the communication network, the arc tolerance problem of the maximum How is proposed. First we study the arc tolerance of the maximum flow in combination with the nature of the maximum How and minimum cut. Secondly we propose an arc tolerance polynomial time algorithm with consideration of arcs in and out of the minimum cut. Finally the proposed algorithm Is analyzed and compared. Numerical example shows that the algorithm has low complexity and Is easy to operate. [ABSTRACT FROM AUTHOR]

Insecticide resistance is an evolutionary adaptation that develops quite quickly in mosquitoes because of the high selection pressure of chemical insecticides, rapid generation time and large population size. Identification of genes associated with insecticide resistance is fundamental to understand the complex processes responsible for resistance. We compared the gene transcriptional profiles of parathion-resistant and -susceptible Culex pipiens quinquefasciatus using a combination of suppression subtractive hybridization and complementary DNA (cDNA) microarray techniques. A total of 278 colonies were selected from the resistant-susceptible mosquito subtractive library, 38 of which showed more than two fold stronger immunoblotting signals in the resistant strain than in the susceptible strain using cDNA microarray selection. The sequencing results showed that the 38 colonies can be matched to 12 genes of C. p. quinquefasciatus. Eight genes were confirmed to be overexpressed by more than two fold in the resistant strain. These genes encode chymotrypsin-1, theta glutathione S-transferase, lipase 3, larval serum protein 1 β chain, cytochrome b, mitochondrial ribosomal large subunit, 28S rRNA, and a protein with unknown function. This study serves as a preliminary attempt to identify new genes associated with organophosphate resistance in this mosquito species and provides insights into the complicated physiological phenomenon of insecticide resistance. [ABSTRACT FROM AUTHOR]

Abstract: Taking Hang Zhou Subway as research background, this article puts forward a new theoretical calculation suitable for subway safety evacuation, which is based on theoretical calculation of Japanese safety evacuation. The theoretical calculation can not only calculate total time necessary for safety evacuation, but also work out people's retention time on the way of different evacuation width clearly to specify the direction of improvement for subway fire-safety design. In addition, the evacuation simulation software named Pathfinder is used to simulate two evacuation situations when the train is stuck in tunnel when there is a fire. In comparison with the evacuation time and simulation result of two evacuation situations by theoretical calculation we can conclude a more accurate time necessary for safety evacuation to provide more reliable data for subway performance-based fire-protection design. [Copyright &y& Elsevier]

The effects of heat treatments on the phase transformation behavior of TiNiFeV and TiNiFeV alloys were investigated. The results indicate that the alloys subjected to different heat treatments have B2 structure at room temperature. All the specimens exhibit a two-stage B2 → R → B19′ martensitic transformation on cooling, but a B19′ → B2 one-stage reverse martensitic transformation on heating except aged A1 alloy, which undergoes an abnormal two-stage transformation upon heating. The phase transformation temperatures are affected by heat treatments and V content, which can be attributed to the variation of the second-phase particles content in the matrix. [ABSTRACT FROM AUTHOR]

The gaut13 gaut14 double mutation altered the distribution of pectin in the pollen tube wall and led to severe defects in pollen tube shape and growth. GAUT13 and GAUT14 may function redundantly on the pectin biosynthesis in pollen tubes.Cell wall biosynthesis is indispensable for pollen tube growth. Despite its importance to sexual reproduction, the molecular mechanisms of pollen tube wall biosynthesis remain poorly understood. Here, we report functional characterization of two putative Arabidopsis galacturonosyltransferase genes, GAUT13 and GAUT14, which are essential for pollen tube growth. GAUT13 and GAUT14 encode the proteins that share a high amino acid sequence identity and are located in the Golgi apparatus. The T-DNA insertion mutants, gaut13 and gaut14, did not exhibit any observable defects, but the gaut13 gaut14 double mutants were defective in pollen tube growth; 35.2–37.3% pollen tubes in the heterozygous double mutants were swollen and defective in elongation. The outer layer of the cell wall did not appear distinctly fibrillar in the double mutant pollen tubes. Furthermore, distribution of homogalacturonan labeled with JIM5 and JIM7 in the double mutant pollen tube wall was significantly altered compared to wild-type. Our results suggest that GAUT13 and GAUT14 function redundantly in pollen tube growth, possibly through participation in pectin biosynthesis of the pollen tube wall. [ABSTRACT FROM PUBLISHER]