Use of MicroRNA Let-7 to Control the Replication Specificity of Oncolytic Adenovirus in Hepatocellular Carcinoma Cells

Highly selective therapy for hepatocellular carcinoma (HCC) remains an unmet medical need. In present study, we found that the tumor suppressor microRNA, let-7 was significantly downregulated in a proportion of primary HCC tissues (12 of 33, 36.4%) and HCC cell lines. In line with this finding, we have engineered a chimeric Ad5/11 fiber oncolytic adenovirus, SG7011let7T, by introducing eight copies of let-7 target sites (let7T) into the 3′ untranslated region of E1A, a key gene associated with adenoviral replication. The results showed that the E1A expression (both RNA and protein levels) of the SG7011let7T was tightly regulated according to the endogenous expression level of the let-7. As contrasted with the wild-type adenovirus and the control virus, the replication of SG7011let7T was distinctly inhibited in normal liver cells lines (i.e. L-02 and WRL-68) expressing high level of let-7 (>300 folds), whereas was almost not impaired in HCC cells (i.e. Hep3B and PLC/PRF/5) with low level of let-7. Consequently, the cytotoxicity of SG7011let7T to normal liver cells was successfully decreased while was almost not attenuated in HCC cells in vitro. The antitumor ability of SG7011let7T in vivo was maintained in mice with Hep3B xenograft tumor, whereas was greatly decreased against the SMMC-7721 xenograft tumor expressing a high level of let-7 similar with L-02 when compared to the wild-type adenovirus. These results suggested that SG7011let7T may be a promising anticancer agent or vector to mediate the expression of therapeutic gene, broadly applicable in the treatment for HCC and other cancers where the let-7 gene is downregulated

Fluid and melt inclusion study on mineralized and barren porphyries, Jinshajiang-Red River alkali-rich intrusive belt, and significance to metallogenesis

Alkali-rich Cu (Au, Mo) deposits are of increasing economic significance and are an attractive exploration target. They include some of the world's highest grade and largest porphyry related gold resources as well as some of the largest gold accumulations in epithermal settings. The Jinshajiang-Red River alkali-rich intrusive belt, with many porphyry Cu (Au, Mo) deposits, is a representative magmatic belt associated with mineralization. The Jinshajiang-Red River alkali-rich intrusive belt contains several Cu (Au, Mo) mineralized alkali-rich porphyry rocks including the Yulong quartz monzonite porphyry, the Machangqing granite porphyry, the Tongchang quartz syenite porphyry, and the Beiya quartz syenite porphyry. Additionally, there are also some barren alkali-rich porphyry rocks in the belt, such as the Yanshuiqing quartz syenite porphyry. Fluid inclusion petrography and microthermometry on those porphyry rocks are carried out in detail. The results show that the fluid inclusion assemblages in ore-bearing and barren porphyries are distinct: inclusions from barren porphyry are dominated by primary melt inclusions, and contain rare or no fluid inclusions, whereas inclusions from ore-bearing porphyries are dominated by fluid inclusions, and contain rare melt inclusions. Furthermore, halite, sylvite, calcite daughter minerals and an opaque phase in fluid inclusions from ore-bearing rocks are common, but rare in fluid inclusions from barren rocks. The results suggests that the evolution of ore forming fluids especially the halite, sylvite, calcite and opaque daughter minerals bearing fluid inclusions of quartz phenocrysts could be used to judge the degree of metasomatism and mineralization of a porphyry system

Nature and evolution of fluid inclusions in the Cenozoic Beiya gold deposit, SW China

The Beiya Au deposit in the Sanjiang metallogenic belt, SW China, is a porphyry-skarn deposit that formed in an intracontinental setting. Three stages of hydrothermal veins, namely quartz veins (Stage 1), quartz-pyrite veins (Stage 2), and Au-rich sulfide-quartz veins (Stage 3) were identified on the basis of field relationship and petrography under scanning electron microscopy cathodoluminescence (SEM-CL). Intermediate density aqueous fluid inclusions (ID1, ID2), high density brine inclusions (B1, B2), and low density vapor inclusions (V1, V2) have been identified in both Stage 1 and Stage 2 veins. Only liquid-rich fluid inclusions (L3) were found in Stage 3 veins. Raman spectroscopy revealed that all the inclusions contain abundant CO2 center dot H2S was identified in ID2 and V2 inclusions. Salinities and homogenization temperatures of the intermediate density aqueous fluid inclusions (ID1, ID2), high density brine inclusions (B1, B2), and low density vapor inclusions (V1, V2) are 7.4 +/- 1.1-11.9 +/- 2.2, 33.6 +/- 0.5-39.2 +/- 1, and 1.6 +/- 0.7-5.8 +/- 0.8 (wt% NaCl equiv.) and 400 +/- 35-440 +/- 37, 395 +/- 20-414 +/- 6, and 386 5-416 +/- 4 degrees C, respectively. Salinities and homogenization temperatures of the L3 inclusions range from 4.9 1.6 to 9.8 0.7 (wt% NaCl equiv) and from 301 28 to 398 4 degrees C, respectively. Initial intermediate density aqueous fluid inclusions contain 2000-10,000 ppm Fe, 2000-4000 ppm Cu, 200-600 ppm Zn, 200-500 ppm Pb, 17-89 ppm Mo, 1-8 ppm Ag, and 0.9-5.9 ppm Au, comparable to that of intermediate density inclusions in subduction-related porphyry deposits. Brine inclusions are rich in metals and have 9000-24600 ppm Fe, 3400-11,000 ppm Cu, 1200-5200 ppm Pb, 500-3000 ppm Zn, hundreds of ppm Mo, and tens of ppm Ag. The corresponding vapor inclusions contain lower metal concentrations: 400-6000 ppm Fe, 1700-4700 ppm Cu, 50-270 ppm Pb, 100-500 ppm Zn, and minor Mo and Ag. Low to intermediate density fluids are abundant and are inferred to have been the main metal transporting medium. A temperature decrease to approximately 350 degrees C during Stage 3 triggered metal precipitation

Nature and evolution of fluid inclusions in the Cenozoic Beiya gold deposit, SW China

The Beiya Au deposit in the Sanjiang metallogenic belt, SW China, is a porphyry-skarn deposit that formed in an intracontinental setting. Three stages of hydrothermal veins, namely quartz veins (Stage 1), quartz-pyrite veins (Stage 2), and Au-rich sulfide-quartz veins (Stage 3) were identified on the basis of field relationship and petrography under scanning electron microscopy cathodoluminescence (SEM-CL). Intermediate density aqueous fluid inclusions (ID1, ID2), high density brine inclusions (B1, B2), and low density vapor inclusions (V1, V2) have been identified in both Stage 1 and Stage 2 veins. Only liquid-rich fluid inclusions (L3) were found in Stage 3 veins. Raman spectroscopy revealed that all the inclusions contain abundant CO2 center dot H2S was identified in ID2 and V2 inclusions. Salinities and homogenization temperatures of the intermediate density aqueous fluid inclusions (ID1, ID2), high density brine inclusions (B1, B2), and low density vapor inclusions (V1, V2) are 7.4 +/- 1.1-11.9 +/- 2.2, 33.6 +/- 0.5-39.2 +/- 1, and 1.6 +/- 0.7-5.8 +/- 0.8 (wt% NaCl equiv.) and 400 +/- 35-440 +/- 37, 395 +/- 20-414 +/- 6, and 386 5-416 +/- 4 degrees C, respectively. Salinities and homogenization temperatures of the L3 inclusions range from 4.9 1.6 to 9.8 0.7 (wt% NaCl equiv) and from 301 28 to 398 4 degrees C, respectively. Initial intermediate density aqueous fluid inclusions contain 2000-10,000 ppm Fe, 2000-4000 ppm Cu, 200-600 ppm Zn, 200-500 ppm Pb, 17-89 ppm Mo, 1-8 ppm Ag, and 0.9-5.9 ppm Au, comparable to that of intermediate density inclusions in subduction-related porphyry deposits. Brine inclusions are rich in metals and have 9000-24600 ppm Fe, 3400-11,000 ppm Cu, 1200-5200 ppm Pb, 500-3000 ppm Zn, hundreds of ppm Mo, and tens of ppm Ag. The corresponding vapor inclusions contain lower metal concentrations: 400-6000 ppm Fe, 1700-4700 ppm Cu, 50-270 ppm Pb, 100-500 ppm Zn, and minor Mo and Ag. Low to intermediate density fluids are abundant and are inferred to have been the main metal transporting medium. A temperature decrease to approximately 350 degrees C during Stage 3 triggered metal precipitation

DP–MHT–TBD: A Dynamic Programming and Multiple Hypothesis Testing-Based Infrared Dim Point Target Detection Algorithm

The detection and tracking of small targets under low signal-to-clutter ratio (SCR) has been a challenging task for infrared search and track (IRST) systems. Track-before-detect (TBD) is a widely-known algorithm which can solve this problem. However, huge computation costs and storage requirements limit its application. To address these issues, a dynamic programming (DP) and multiple hypothesis testing (MHT)-based infrared dim point target detection algorithm (DP–MHT–TBD) is proposed. It consists of three parts. (1) For each pixel in current frame, the second power optimal merit function-based DP is designed and performed in eight search areas to find the target search area that contains the real target trajectory. (2) In the target search area, the parallel MHT model is designed to save the tree-structured trajectory space, and a two-stage strategy is designed to mitigate the contradiction between the redundant trajectories and the requirements of more trajectories under low SCR. After constant false alarm segmentation of the energy accumulation map, the preliminary candidate points can be obtained. (3) The target tracking method is designed to eliminate false alarms. In this work, an efficient second power optimal merit function-based DP is designed to find the target search area for each pixel, which greatly reduces the trajectory search space. A two-stage MHT model, in which pruning for the tree-structured trajectory space is avoided and all trajectories can be processed in parallel, is designed to further reduce the hypothesis space exponentially. This model greatly reduces computational complexity and saves storage space, improving the engineering application of the TBD method. The DP–MHT–TBD not only takes advantage of the small computation amount of DP and high accuracy of an exhaustive search but also utilizes a novel structure. It can detect a single infrared point target when the SCR is 1.5 with detection probability above 90% and a false alarm rate below 0.01%

Influence of water temperature, habitat complexity and light on the predatory performance of the dark sleeperOdontobutis potamophila(Gunther, 1861)

Recently, the dark sleeper [Odontobutis potamophila(Gunther, 1861)] was selected as a potential aquaculture target. However, the feeding behavior of this species remains unclear. In this study, we investigated the influence of water temperature, habitat type, light intensity and photoperiod on the predatory performance of dark sleepers against juvenile demersal mrigal carp [Cirrhinus mrigala(Hamilton, 1822)] in the laboratory. Our results showed that both the prey consumption and the feeding rate of dark sleepers increased significantly with increases in water temperature (22-34 degrees C) and stabilized between 26-34 degrees C. Additionally, both the prey consumption and the feeding rate were higher in vegetated habitats than those in open areas at 22-30 degrees C, although no significant differences were detected. The prey consumption and the feeding rate of dark sleepers increased significantly with decreased light intensity (0-1350 lx) and shortened light duration (0-14 h), indicating that this fish prefers feeding in dark environments. These results will help elucidate the influence of environmental variables on this species' predatory performance and create suitable protocols for its culture

The regulation effect of let-7 target sites on upstream gene, analyzed by dual-luciferase assay system.

<p>The relative Renilla/Firefly ratio of cells transfected with the control plasmid, psiCHECK2 was set to 100%. The Renilla/Firefly values of cells transfected with psiCHECK2-Let7T or psiCHECK2-Let7MT was normalized to its corresponding value of cells transfected with psiCHECK2 in a same independent experiment, respectively. Duplicated experiments were conducted from the procedure of cell culture. Error bars correspond to mean ± SD. n = 3. (^** P<0.01).</p

Univariate Analysis of let-7a Expression and Clinicopathological Risk Factors in Patients with HCC.

a<p>The let-7a expression of primary HCC tissues relative to normal liver tissues.</p>b<p>The correlation coefficient between types of each clinicopathological risk factors and the three status of let-7a expression (i.e. decreased, increased, or unaltered).</p