Dictamnine inhibits pancreatic cancer cell growth and epithelial-mesenchymal transition by blocking the PI3K/AKT signaling pathway.

Many different treatments are available for pancreatic cancer (PC), including surgical resection, chemotherapy, radiotherapy, and immunotherapy, but these treatments are often ineffective at curing PC. Hence, identifying new and effective agents or strategies to improve therapeutic effects is critical. This study focused on the efficacy of dictamnine (DTM), a furan quinoline alkaloid extracted from Dictamnus dasycarpus Turcz., in treating PC. Our in vitro results showed that DTM can mitigate cell proliferation and induce cell cycle arrest and apoptosis in two different human PC cell lines. Moreover, epithelial-mesenchymal transition (EMT) was prevented during DTM treatment, reflected by reduced cell migration and invasion abilities. In vivo studies demonstrated that DTM treatment led to a remarkable inhibition of tumor growth in a xenograft nude mouse model. Mechanistic investigation showed that DTM might act by restraining constitutive and induced PI3K/AKT activity. In summary, our results demonstrated that DTM slows PC progression by inhibiting the activity of the PI3K/AKT signaling pathway and its downstream effectors and that DTM is effective as a pathway-specific cancer therapy. These findings could provide a greater understanding of the function of anticancer drugs and new options for PC treatment.

Iterative deformation calibration of a transmission flat via the ring-point support on a 300-mm-aperture vertical Fizeau interferometer.

In the development of a high-precision vertical Fizeau interferometer with a 300-mm aperture, the deformation of the transmission flat because of clamping and gravity must be considered. In this paper, we proposed a ring-point support scheme for the deformation calibration of a large-diameter transmission flat. The calibration theory of the ring-point support system with elastic deformation was derived. The changes in the surface and stress field of the transmission flat were analyzed quantitatively by finite element method modeling, leading to the optimization of the support structure. To validate the proposed calibration approach, we performed an absolute test of the transmission flat using a liquid reference. The test result was compared to a measurement of the Zygo interferometer demonstrating the effectiveness of the proposed ring-point support design. Finally, with the iterative deformation calibration, the accuracy of the transmission flat reached λ/25 (Peak Valley, PV) for a 300-mm aperture.

System design and error correction for 300 mm aperture vertical Fizeau spatial-temporal phase-shifting interferometer.

With the development of high-power lasers for aerospace, electronics, etc., the demand for large-aperture planar optical elements has become more urgent, along with the demand for measurement methods. In this paper, the design of a 300 mm aperture vertical Fizeau spatial-temporal phase-shifting interferometer is discussed. Based on position difference between laser sources, the spatial phase-shifting technique is achieved by generating a laser source array on the focal plane of the collimation lens, and four pairs of coherent beams with different phase shifts are integrated in a vertical Fizeau interference system. Combined with a tunable laser diode, a temporal phase-shifting technique can be realized in any pair of coherent beams through wavelength tuning. The key techniques, which include laser duplication to introduce different phase shifts, conjugate imaging, and separation for interferograms, and assembly for a transmission flat, are demonstrated. The systematic error and position mismatch error of interferograms are eliminated. Comparison experiments are conducted between spatial and temporal phase-shifting techniques. A dynamic water surface is also measured to verify its capacity for detecting dynamic objects.

The path to triacylglyceride obesity in the sta6 strain of Chlamydomonas reinhardtii.

When the sta6 (starch-null) strain of the green microalga Chlamydomonas reinhardtii is nitrogen starved in acetate and then "boosted" after 2 days with additional acetate, the cells become "obese" after 8 days, with triacylglyceride (TAG)-filled lipid bodies filling their cytoplasm and chloroplasts. To assess the transcriptional correlates of this response, the sta6 strain and the starch-forming cw15 strain were subjected to RNA-Seq analysis during the 2 days prior and 2 days after the boost, and the data were compared with published reports using other strains and growth conditions. During the 2 h after the boost, ∼425 genes are upregulated ≥2-fold and ∼875 genes are downregulated ≥2-fold in each strain. Expression of a small subset of "sensitive" genes, encoding enzymes involved in the glyoxylate and Calvin-Benson cycles, gluconeogenesis, and the pentose phosphate pathway, is responsive to culture conditions and genetic background as well as to boosting. Four genes-encoding a diacylglycerol acyltransferase (DGTT2), a glycerol-3-P dehydrogenase (GPD3), and two candidate lipases (Cre03.g155250 and Cre17.g735600)-are selectively upregulated in the sta6 strain. Although the bulk rate of acetate depletion from the medium is not boost enhanced, three candidate acetate permease-encoding genes in the GPR1/FUN34/YaaH superfamily are boost upregulated, and 13 of the "sensitive" genes are strongly responsive to the cell's acetate status. A cohort of 64 autophagy-related genes is downregulated by the boost. Our results indicate that the boost serves both to avert an autophagy program and to prolong the operation of key pathways that shuttle carbon from acetate into storage lipid, the combined outcome being enhanced TAG accumulation, notably in the sta6 strain.

Determinants of growth and carbon accumulation of common plantation tree species in the three northern regions, China: Responses to climate and management strategies.

The Three-North (Northwest, North and Northeast) Shelter Forests Program (TNSFP) in China has effectively promoted vegetation growth and carbon sink in the temperate semi-humid and semi-arid regions. To compare the afforestation benefits of commonly used tree species in the area and explore the effect of environment on growth and carbon accumulation in plantations, backpack LiDAR was used to acquire 3 dimensional lidar point clouds of forests from a total of 480 pure plantation patches consisting of Pinus sylvestris (P.s.), Pinus tabuliformis (P.t.), Populus spp. (Pop.), and Robinia pseudoacacia (R.p.). Then, diameter at breast height (DBH), forest height, canopy coverage, and aboveground carbon accumulation were calculated for each plantation patches, which ranged from 7.0 to 37.3 cm, 1.5-14.5 m, 10-99 % and 4.2-205.9 Mg/ha, respectively. Generalized linear mixed-effect models and ANOVA were applied to account for the environmental constraints on the variations of forest parameters. Results showed that precipitation had a stronger effect on all the above parameters of plantations than temperature, and P.t. was more sensitive to climate than other three species. With regard to forest management in Pop. plantations, thinning could improve afforestation efficiency because carbon accumulation would reduce after the age exceeds 30 years. In contrast, P.s. populations maintained a continuous increase in carbon accumulation at least before 40 years old, while the radial growth of canopy became saturated after 12 years of age. The optimal planting density for P.s. and Pop. are about 1000 trees/ha, beyond which the increase in carbon accumulation will slow down or change rate of canopy coverage will be insignificant. Within the TNSFP area, P.t. and R.p. plantations would be more suitable in southern regions, while P.s. and Pop. plantations grow better in the northeastern regions. Meanwhile, mountains along the "Hu Line" showed high potential for growth and carbon accumulation for all tree species examined.

VIPR: A probabilistic algorithm for analysis of microbial detection microarrays.

BACKGROUND: All infectious disease oriented clinical diagnostic assays in use today focus on detecting the presence of a single, well defined target agent or a set of agents. In recent years, microarray-based diagnostics have been developed that greatly facilitate the highly parallel detection of multiple microbes that may be present in a given clinical specimen. While several algorithms have been described for interpretation of diagnostic microarrays, none of the existing approaches is capable of incorporating training data generated from positive control samples to improve performance. RESULTS: To specifically address this issue we have developed a novel interpretive algorithm, VIPR (Viral Identification using a PRobabilistic algorithm), which uses Bayesian inference to capitalize on empirical training data to optimize detection sensitivity. To illustrate this approach, we have focused on the detection of viruses that cause hemorrhagic fever (HF) using a custom HF-virus microarray. VIPR was used to analyze 110 empirical microarray hybridizations generated from 33 distinct virus species. An accuracy of 94% was achieved as measured by leave-one-out cross validation. CONCLUSIONS: VIPR outperformed previously described algorithms for this dataset. The VIPR algorithm has potential to be broadly applicable to clinical diagnostic settings, wherein positive controls are typically readily available for generation of training data.

[Biological characteristics and antitumor activity of CIK cells activated by recombinant human fibronectin for human lung cancer cell lines in vitro].

BACKGROUND AND OBJECTIVE: The CIK cell is one of the most important means of the adoptive cellular immunotherapy, and it is a hotspot of which to simplify its culture procedure and to promote its inhibition rate. The aim of this study is to observe the biological function of the CIK cells cultivated by the recombinant human fibronectin (RN) and to establish an effective and simple way of cells expansion. METHODS: We separated the mononuclear cells (PBMCs) in 50 mL peripheral blood from 10 healthy persons with density gradient centrifugation in the lymphocyte-separating medium, and the PBMCs were divided into two groups, of which were cultivated by RN-introduced and conventional method separately. Then we estimated the proliferation ability, and analyzed the immunologic type, IFN-gamma, IL-4, perforin and granzyme B of them with flow cytometry. Besides that, we tested the inhibition rate of CIKs cells to four kinds of human lung cancer cell lines in vitro by MTT assay. RESULTS: The RN-induced group had a higher proliferation rate that was 2.0-3.5 times of the conventional group, and there was an obvious statistical difference between the two (P < 0.05). The proliferation rates of CD3+CD16+CD56+T cells in each group were 3 778 and 2 068 times of the initial number, respectively. There was also a higher percentage of CD3+CD8+ T cells in RN-induced group (P < 0.05), while the percentage of CD3+CD4+T cells had no significant statistical difference (P > 0.05). We found a similar inhibition rate of the CIK cells to all this human lung cancer cell lines (P > 0.05). The cells which secreted IFN-gamma increased, while the cells which secreted IL-4 did not. The cells which secreted granzyme B and perforin were positive. CONCLUSION: It is an effective and simple way to cultivate the CIK cells with RN, which should be adopted.

[The systemic evaluation and clinical significance of immunological function for advanced lung cancer patients].

BACKGROUND AND OBJECTIVE: The actual evaluation of immunological function is significant for studing the tumor development and devising a treatment in time. The aim of this study is to evaluate the immunological function of advanced lung cancer patients systematically, and to discuss the clinical significance. METHODS: The nucleated cell amounts of advanced lung cancer patients and the healthy individuals were counted. The immune cell subsets and the levels of IL-4, INF-gamma, perforin and granzyme in CD8+T cells by the flow cytometry were measured. The proliferation activity and the inhibition ratio of immune cells to several tumor cell lines were evaluated by MTT assay. RESULTS: The absolute amounts and subsets of T, B, NK cells of advanced lung cancer patients were lower than the healthy individuals (P < 0.05); However, the proportion of regulatory T cells of advanced lung cancer patients (4.00 +/- 1.84)% was lower than the healthy individuals (1.27 +/- 0.78)% (P < 0.05). The positive rates of IFN-gamma perforin, granzyme in CD8+T cells decreased while them in IL-4 did not in the advanced lung cancer patients compared to the healthy control group (P < 0.05). The proliferation activity of immune cells, the positive rate of PPD masculine and the inhibition ratio to tumor cells in the advanced lung cancer patients was lower than the healthy subsets obviously (P < 0.05). CONCLUSION: There was a significant immune depression in the advanced lung cancer patients compared to the healthy individuals.

Transgene-induced RNA interference as a tool for plant functional genomics.

RNA interference (RNAi) is a powerful tool for functional genomics in a number of species. The logistics and procedures for doing high-throughput RNAi to investigate the functions of large numbers of genes in Arabidopsis thaliana and in Zea mays are described. Publicly available plasmid vectors that facilitate the stable chromosomal integration of inverted repeat transgenes that trigger RNAi have been used to generate more than 50 independent transgenic lines each in Arabidopsis and maize. Analysis of mRNA abundance of the targeted genes in independent lines transformed with distinct constructs indicates that the success of RNAi-induced silencing is gene dependent. mRNA levels were not detectably reduced for some genes, but were dramatically reduced for a number of genes targeted. A common pattern was that multiple independent lines transgenic for the same construct showed the same extent of silencing. This chapter describes the procedures used to generate and test transgenic lines mediating RNAi in Arabidopsis and maize.