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Twenty-five novel 2,4,6-trisubstituted triazines were synthesized and biologically evaluated. Most of the compounds synthesized showed good antiproliferative activity against HCT-116 and MCF-7. Compounds B18 and B19 showed the best antiproliferative activity. Further study showed B18 and B19 inhibited four phosphoinositide 3-kinase isoforms and mammalian target of rapamycin with good potency. These results demonstrate that 2,4,6-trisubstituted triazines are potentially useful phosphoinositide 3-kinase inhibitors for the development of new anticancer drugs.

Small-molecule targeted antitumor drugs are considered to be a promising treatment that can improve the efficacy and reduce side effects. PI3K/Akt signaling pathway is constantly activated in various cancers. We recently synthesized a series of novel compounds of PI3K/Akt pathway inhibitors and found the most effective analog to be W934. In this study, we explored the in-vitro and in-vivo antitumor effects of W934 on A549 non-small-cell lung cancer cells and HCT116 colorectal cancer cells. In-vitro assays showed that W934 caused an inhibition of PI3Kα kinase. W934 can significantly suppress the viability of A549 and HCT116 cells with IC50 values of 0.25 and 0.23 μmol/l, respectively. Besides, the inhibitory effects on cell migration, invasion and apoptosis were also observed after treatment of W934 for the indicated hours. According to the cell cycle analysis, W934 caused an inhibition of G0-G1 phase progression and correspondingly decreased the percentage of cells in S and G2-M phases. Results of western blotting indicated that W934 concentration dependently suppressed the activation of the PI3K/Akt pathway. Meanwhile, the in-vivo effect was studied in an A549 xenograft mouse model. Oral administration of W934 inhibited the tumor growth in a dose-dependent manner. Hereby, W934 might be considered as a potential therapeutic drug candidate for non-small-cell lung cancer treatment.

Heavy metals (HMs) are naturally occurring elements that have high natural background levels in the environment. Therefore, it is important to conduct ecological risk assessment and identify potential sources of HMs. In the past, studies were conducted at the regional scale. The accuracy of those studies could not meet the needs of spatial planning and natural resource management. Therefore, it is necessary to conduct ecological risk assessment at the township scale. In this study, 1092 soil samples (from 0-20 cm depth) were collected in the town of Reshui, an area with high background levels of soil HMs with the parent material of carbonatite, which is commonly found in Southwest China. The town of Reshui is a multi-ecological risk superimposed area where the ecological risk is high. In this study, concentrations of HMs (Cd, Cr, As, Hg, Pb, Cu, Zn, and Ni) in the topsoil were analyzed, and statistical analysis (SA), geographic information system (GIS) modeling, and positive matrix factorization (PMF) analysis were performed. The geoaccumulation index (

Different light qualities have been found to effectively promote polysaccharide production of cyanobacteria, to elucidate the underlying mechanism, the effects of four typical light qualities including ultraviolet radiation B (UVB), red light (R), blue light (B), and mixed light (R:B = 7:15) (RB) on polysaccharide production in Nostoc flagelliforme were comprehensively investigated with white fluorescent light as control. In this study, an iTRAQ-based proteomic approach was employed to explore the proteomes of N. flagelliforme, and 126, 177, 208, and 200 differentially expressed proteins were identified in UVB-, R-, B- and RB-treated N. flagelliforme. Functional classification analysis showed that differentially expressed proteins were mainly involved in photosynthesis, antioxidant activity, and carbohydrate metabolism. Analysis of differentially expressed proteins involved in polysaccharide synthesis revealed that different light qualities shared a common mechanism to promote polysaccharide production by altering carbon allocation and increasing carbon flow into sugar nucleotide synthesis pathway. Activity assay of selected enzymes further verified the proteomic analysis. Our results provide novel insights into the molecular mechanisms of light quality affecting polysaccharide production.

Nostoc flagelliforme is a pioneer organism in the desert and exerts important ecological functions. The habitats of N. flagelliforme are characterized by intense solar radiation, while the ultraviolet B (UV-B) tolerance has not been fully explored yet. To evaluate the physiological responses of N. flagelliforme to UV-B radiation, three intensities (1 W m−2, 3 W m−2 and 5 W m−2) were used, and the changes in photosynthetic pigments, cell morphology, mycosporine-like amino acids (MAAs) synthesis and cell metabolism were comparatively investigated. Under high UV-B intensity or long term radiation, chlorophyll a, allophycocyanin and phycocyanin were greatly decreased; scanning electron microscope observations showed that cell morphology significantly changed. To reduce the damage, cells synthesized a large amount of carotenoid. Moreover, three kinds of MAAs were identified, and their concentrations varied with the changes of UV-B intensity. Under 1 W m−2 radiation, cells synthesized shinorine and porphyra-334 against UV-B, while with the increase of intensity, more shinorine turned into asterine-330. Metabolite profiling revealed the contents of some cytoprotective metabolites were greatly increased under 5 W m−2 radiation. The principal component analysis showed cells exposed to UV-B were metabolically distinct from the control sample, and the influence on metabolism was particularly dependent on intensity. The results would improve the understanding of physiological responses of N. flagelliforme to UV-B radiation and provide an important theoretical basis for applying this organism to control desertification.

Clinical interpretation of the test results for cortisol based on continuous reference intervals with appropriate partitions improves pediatric diagnosis; however, these values are available only for Caucasians. To develop the pediatric reference intervals for Chinese population, we examined the serum cortisol levels in 1,143 healthy Chinese children aged 4-18 years (566 boys and 577 girls), using an IMMULITE 2000 Immunoassay System (Siemens Healthcare GmbH). Phlebotomy was performed at 7-9 a.m. for 284 boys and 287 girls and at 1-3 p.m. for the others. They were divided into four age groups according to the Clinical and Laboratory Standards Institute guideline EP28-A3c, with the last group further stratified according to sampling time. Separate reference intervals of 49.6-323.7, 70.9-395.3, and 90.1-448.7 nmol/L were established for children aged 4-8, 9-12, and 13-15 years, respectively. Further, reference intervals of 118.2-464.7 and 71.4-446.7 nmol/L were established for morning and afternoon cortisol levels, respectively, in children aged 16-18 years. Further studies are necessary to transfer and validate these reference intervals in other analytical systems and pediatric populations, and to allow for broader applications.

2-(Pyridin-2-yl) aniline was designed as a new, removable directing group in promoting C–H amination mediated by cupric acetate. Employing this auxiliary, the β-C(sp2)–H bonds of benzamide derivatives can be effectively aminated with a variety of amines in moderate to good yields with good functional group tolerance in air. In addition, the quinazolinone derivatives were isolated from the reaction mixture of N-(2-(pyridin-2-yl)phenyl)benzamide with formamide or 5-nitroindole. The corresponding mechanism is discussed. These results indicate that 2-(pyridine-2-yl)aniline can serve as a directing group.

The strategy of light environment control was applied to improve biomass and extracellular polysaccharides (EPS) production of the cyanobacterium Nostoc flagelliforme by adjusting multiple wavelengths (red 660 nm, blue 460 nm, green 520 nm) and light intensity assisted by nitrogen source optimization. A mixed wavelength with low light intensity was more suitable for cell growth. Wavelength shift approach, i.e., manipulation of light wavelength at appropriate culture stages, increased both biomass and EPS production, and optimum shift time was at 9 days. The effects of four nitrogen sources under different light conditions were subsequently evaluated, and urea showed the best performance. The optimized wavelength shift approach (9-day illumination with white light followed by 9-day culture with mixed wavelengths of red/blue/green = 12:5:5) with urea as nitrogen source improved the biomass from 0.72 ± 0.02 to 1.20 ± 0.02 g L−1 (i.e., by 66 %) and EPS production from 27.31 ± 1.00 to 86.65 ± 2.56 mg L−1 (i.e., by 217.3 %). These results provide information on novel culture strategies for microalgal biotechnology by applying light environment control.

Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+ bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.

Aim: The discovery and development of novel agents simultaneously targeting PI3K/AKT/mammalian target of rapamycin and Ras/RAF/MEK, two signaling pathways, are urgent to improve the curative effect of kinase inhibitors and overcome acquired resistance. Methods/results: In the present study, 2-(2-aminopyrimidin-5-yl)-4-(morpholin-4-yl)-6-(N-cyclopropyl-N- (1-benzoylpiperidin-4-yl))triazines/pyrimidines were designed as PI3K and BRAF dual inhibitors. The synthesized 20 compounds exhibited potent antiproliferative effects in vitro against HCT116, A375, MCF-7, Colo205, A549 and LOVO cancer cell lines. The tested compounds A6, A7, A9 and A11 remarkably displayed inhibitory activities toward both PI3Kα and BRAFV600E. Conclusion: These results indicated that our design compounds can serve as potent PI3Kα and BRAFV600E dual inhibitors and effective antiproliferative agents, which can be further optimized to discover more potent PI3Kα and BRAFV600E dual inhibitors.

Filamentous Nostoc flagelliforme form colloidal complex, with beaded cells interacting with other bacteria embedded in the complex multilayer sheath. However, the species of bacteria in the sheath and the interaction between N. flagelliforme and associated bacteria remain unclear. In this study, PCR-denaturing gradient gel electrophoresis (DGGE) was used to investigate the bacterial communities of N. flagelliforme from three regions of China. DGGE patterns showed variations in all samples, exhibiting 25 discrete bands with various intensities. The diversity index analysis of bands profiles suggested the high similarity of bacterial communities to each other but also the dependence of microbial composition on each location. Phylogenetic affiliation indicated that the majority of the sequences obtained were affiliated with Actinobacteria, Cyanobacteria, Proteobacteria, Acidobacteria, Bacteroidetes, of which Cyanobacteria was dominant, followed the Proteobacteria. Members of the genus Nostoc were the most abundant in all samples. Rhizobiales and Actinobacteria were identified, whereas, Craurococcus, Caulobacter, Pseudomonas, Terriglobus and Mucilaginibacter were also identified at low levels. Through comparing the bacterial composition of N. flagelliforme from different regions, it was revealed that N. flagelliforme could facilitate the growth of other microorganisms including both autotrophic bacteria and heterotrophic ones and positively contributed to their harsh ecosystems. The results indicated N. flagelliforme played an important role in diversifying the microbial community composition and had potential application in soil desertification.

Light quality strongly affects cell growth and polysaccharide production of cyanobacteria, however, the metabolic mechanism of polysaccharide biosynthesis upon light quality has not been fully explored yet. The effects of light quality on the metabolic changes of Nostoc flagelliforme were comprehensively investigated using red, yellow, green, blue, purple light emitting diodes for illumination. The principal component analysis revealed that red, yellow, green, blue, and purple light-grown cells were metabolically distinct from those illuminated with white fluorescent light, and the influence of light quality on metabolism was particularly dependent on light wavelength. Significant correlations between the metabolic profile and extracellular polysaccharide (EPS) and capsular polysaccharide (CPS) production were revealed by partial least-squares to latent structure analysis respectively, and analysis of key metabolites showed that CPS production was closely related with cell growth while the biosynthesis of EPS was more closely related with light conditions. Furthermore, as the influence pattern of red light on cellular metabolism and polysaccharide production was quite different from other light conditions, the effects of intensity of red light on photosynthesis and polysaccharide production were evaluated, and the results revealed that red light induced photoinhibition and therefore stimulated polysaccharide production. Manipulation of red light was thus proposed to profitably enhance polysaccharide productivity of N. flagelliforme.

Neurofibromatosis type 1 (NF1), caused by germ line mutations of the NF1 tumor-suppressor gene, is one of the most common autosomal dominant disorders. Here, we reported a NF1 patient with the mutation NF1 c.4367+1G>C. This sequence change locates at the first nucleotide of NF1 intron 32 within the consensus splice site. Compared with NF1 c.4367G>C predicted to potentially damage the wild-type donor site at c.4367, the NF1 c.4367+1G>C potentially abolishes this wild-type donor site by in silico analysis. In vitro minigene assay revealed that the NF1 c.4367+1G>C may cause exon 32 skipping. Our result provides further evidence for its clinical significance of NF1 c.4367+1G>C in clinical practise.

Targeting acquired drug resistance is the major challenge in the treatment of EGFR-driven non-small cell lung cancer (NSCLC). In this study, a novel class of compounds containing pyrido[3,4-d]pyrimidine scaffold was designed as new generation EGFR-TKIs to overcome this challenge. The most promising compound B30 inhibited HCC827 and H1975 cells growth with the IC50 values of 0.044 μM and 0.40 μM, respectively. Meanwhile, B30 displayed potent inhibitory activity against the EGFRL858R (IC50 = 1.1 nM) and EGFRL858R/T790M/C797S (IC50 = 7.2 nM). B30 could suppress EGFR phosphorylation in a dose-dependent manner in HCC827 cell line and significantly induce the apoptosis of HCC827 cells. Molecular docking indicated that the hydroxyl in B30 could form additional hydrogen bond with mutant Ser797. These findings strongly support our assumption that 2,4,6-trisubstitued pyrido[3,4-d] pyrimidine derivatives can serve as EGFR-TKIs. The predicted hydrogen bond interaction formed by a small molecule inhibitor with mutant Ser797 is available to design the fourth-generation EGFR-TKIs.

2-(Pyridin-2-yl) aniline was designed as a new, removable directing group in promoting C-H amination mediated by cupric acetate. Employing this auxiliary, the β-C(sp

The system proposed in this study deals with pedestrian counting and detection in intelligent video surveillance systems. It is a hybrid of map-based and detection-based approaches, and combines the advantages of both. After the foreground objects being segmented, the map-based module, which implicitly compensates the perspective distortion by integrally projecting the features onto a given direction, is triggered to estimate the number of pedestrians in each foreground region. Then, a class-specific Hough forest is employed to locate individuals. Experimental results have validated our strategy. The proposed map-based module has the ability of accurately estimating the count for each region. Also, the estimation can speed up the process of locating individuals by providing cues like the number of targets and the approximate size of each target. The proposed detection-based module not only locates pedestrians, but deals with enhancing the accuracy of the counting as well.

An efficient, convenient Cu-catalyzed formation of chromeno[4,3-c]pyrazol-4(1H)-ones is reported. In this atom economic process, readily available 3-acylcoumarin hydrazone is oxidative cyclized by direct C–N bond formation. Air has been successfully used as an oxidant, which has important economic and environmental advantages. A broad scope of 3-acylcoumarin hydrazones can be utilized in this process.

An exopolysaccharide (LEP-2b) with molecular weight of 2.8×10(4)Da was isolated from Lachnum YM405 and purified by DEAE-cellulose 52, Sepharose CL-6B chromatographic column. It consisted of rhamnose (Rha), mannose (Man), glucose (Glc) and galactose (Gal) in a molar ratio of 1.0:5.0:11.5:12.5. Its backbone consisted of →4)-β-d-Manp-(1→, →2)-α-d-Rhap-(1→, →6)-β-d-Glcp-(1→, and →6)-α-d-Galp-(1→, and three types of branches were composed of →6)-α-d-1-OMe-Manf-(2→, →6)-β-d-1-OMe-Manf-(2→, →1)-α-d-Galp-(6→, →1)-β-d-Galp-(6→, and →1)-β-d-Glcp, which were at O-3 of 1,3,6-linked α-d-Manp and O-2, O-3 of the same 1,2,3,6-linked β-d-Glcp in the backbone respectively. LEP-2b ointment significantly accelerated the decrustation of the wounded skin, shortened the healing time and increased the water and hydroxyproline contents of the healed skin. Combined with the results of macroscopic and histological observations, we deemed that LEP-2b could inhibit inflammatory reaction of scalded skin, accelerate tissue repair and re-epithelialization, thereby playing a positive role in promoting wound healing.

A series of chromeno[4,3-d]pyrazolo[3,4-b]pyridin-6(3H)-one derivatives was easily and efficiently synthesized by the reaction of 2H-chromen-2-ones with pyrazol-5-amines catalyzed by CuCl2⋅2H2O in ethanol. This protocol has the advantages of mild reaction conditions, easy work-up, and high yields. These compounds were showed to have high fluorescence quantum yields, which mentioned their value as luminescence or fluorescence probe.

The adsorption property of Cu2+ in aqueous solution by carbonaceous adsorbent made by sludge was studied. Under static conditions, the influences to the adsorption properties by the dosage of adsorbent, adsorption time, concentration of Cu2+, adsorption temperature, pH value, and other factors were systematically studied. The adsorption kinetics of the carbonaceous adsorbent was analyzed, and its adsorption properties were primarily discussed. The research results show that the carbonaceous adsorbent made by sludge has strong removal efficiency of Cu2+; the adsorption process complies with the Fruendlich adsorption isotherm; and the adsorption process can be represented by first-order kinetic model.

A facile and efficient one-pot procedure for the preparation of functionalized dihydro-1H-indol-4(5H)-ones by a catalyst-free, three-component reaction of 1,3-dicarbonyl compounds, arylglyoxal monohydrate and enaminones under mild conditions in excellent yield is reported. This synthesis was confirmed to follow the group-assisted-purification (GAP) chemistry process, which can avoid traditional purifications, chromatography, and recrystallization.

Chicken β-defensin Gal-3 was recently identified member of a family of antimicrobial peptides. In this paper, the sequences of the chicken β-defensin Gal-3 gene was replaced with plant preferred codons by Polymerase Chain Reaction, and cloned into the plant expression vector p1390R, then transferred into alfalfa by Agrobacterium tumefacien- mediated method. PCR was performed by using the genomic DNA of transgenic alfalfa as template, which showed that Gal-3 has been transferred into alfalfa. Therefore, the suitable concentration of Hyg for screening transformants was 20 mg/L. The 4 trangenic plants were analyzed by Southern hybridization.

The expression level of chicken β-defensin Gal-3 was influenced by lactose concentration, induction time and initial cell density, and IPTG induction was used as a control. The optimal parameters of various factors were confirmed. the optimal parameters with lactose induction was 37°C of culture temperature, 2 g/L of joining lactose final concentration when the recombinant strain growth density A600 achieved 0.8 and induction maintained 3 hours, the production of fusion protein reached the highest level. This study provides a good experimental basis for the large production of Gal-3.

Tumor is a kind of disease with higher morbidity and mortality, which is currently a serious threat to human health, and to strengthen the prevention and treatment of neoplastic diseases has important economic and social benefits. The migration behavior of tumor cell is a key link in the process of tumor metastasis. In this study, the related cellular and molecular mechanisms of MRTF and AQP1 inducing the migration of colon cancer cells HT-29 were revealed in the respect of Gene transcription regulation. This heralded that MRTF and AQP1 could probably be a new target on treating the tumor cell migration.

Background Giardia lamblia is one of the most common infectious protozoans in human that may cause diarrhea in travelers. Searching for antigens that induced effectively protective immunity has become a key point in the development of vaccine against giardiasis. Methodology/Principal Findings Mice vaccinated with G. lamblia trophozozite-specific α1-giardin DNA vaccine delivered orally by attenuated Salmonella typhimurium SL7027 elicited 74.2% trophozoite reduction, but only 28% reduction in cyst shedding compared with PBS buffer control. Oral vaccination with Salmonella-delivered cyst-specific CWP2 DNA produced 89% reduction in cysts shedding in feces of vaccinated mice. Significantly, the mice vaccinated with Salmonella-delivered bivalent α1-giardin and CWP2 DNA vaccines produced significant reduction in both trophozoite (79%) and cyst (93%) in feces of vaccinated mice. This parasite reduction is associated with the strong local mucosal IgA secretion and the IgG2a-dominant systemic immune responses in vaccinated mice. Conclusions The results demonstrate that bivalent vaccines targeting α1-giardin and CWP2 can protect mice against the colonization of Giardia trophozoite and block the transformation of cyst in host at the same time, and can be used to prevent Giardia infection and block the transmission of giardiasis.

Regional comprehensive disaster prevention and mitigation planning is to evaluate the disaster risk and disaster resistance capability of a region based on the investigation and prediction of existed or potential disasters in this region, and after that the planning will construct a comprehensive defense system to avoid or reduce the economic loss of disaster and improve the disaster prevention capability. Tanghai County comprehensive disaster prevention and mitigation planning evaluates disaster resistance of all units of county and disaster mitigation of disaster-prevention projects, and it emphasizes on comprehensive disaster prevention and mitigation planning in key regions. This planning will improve the disaster prevention capability of local government, reduces disaster risk and ensures the sustainable development of economic and environment for that county.

The liquid-solid two-phase turbulent flow in an axial flow pump was numerically simulated by using the SIMPLEC algorithm based Navier-Stoker and RNG k-ε turbulent model and after the secondary development of the software Fluent. The distributions of solid concentration, velocity and pressure on the impellers of the axial flow pump were analyzed at different volume concentrations at the pump inlet. The numerical results show that the head and the efficiency of the pump will reduce with the increasing of the sediment concentration in sandy rivers. This research shows that the numerical simulation results are consistent with the actual situations.

A series of 4-aryl-3,7,7-trimethyl-1-phenyl-7,8-dihydro-1H-pyrazolo[3,4-b]quinolin- 5(6H)-ones were synthesized by the three-component reaction of aromatic aldehydes, 3-methyl-1-phenyl-1H-pyrazol-5-amine, and 5,5-dimethyl-1,3-cyclohexandione in the presence of sodium 1-dodecanesulfonate in aqueous medium. Compared to the previous methods, this new protocol has the advantages of convenient operation, higher yields, lower cost, and environmentally benign procedure. J. Heterocyclic Chem., (2012).

To obtain the optimal path in a unknown disaster field,a rescue robot needs to build an environment map. The information of the disaster field is collected by the sonsors of different robots, all signal from sensors (mounted on all robots and signal form GPS) are sent to the bakeside parllel processors with wireless network. A grid computing environment serves as the backside parallel processors with Globus Toolkit, the grid computing processor process all the signals and construct the global map to help robot for navigation path planning.The rescue robot get control signal from the grid computing processor with wireless network,thus, the robot is not necessary to be sophisticated. New computing methods are given for parallel algorithm on grid environment. The navigation control is implemented with the cooperation among heterogeneous agents, the advantages of large seale computing on grid are shown.

Despite the quality of engineers that still universities are forming, the existing system for educating engineers must change, provides the courses for engineering educators, and a large experience developing and implementing engineering programs, the engineering education research team has decided to develop and to offer a graduation level program for engineers dedicated to education. Through the application of computer-mediated communication educators or instructional designers in the field of engineering with an opportunity to share the ideas and experience of innovating curriculum and instructional methods of engineering education. In this paper, we briefly review the status of engineering education in China. Additionally, we provide details of how these concepts can be used in an educational model, a learning system is also believed to be the stepping stone to one that generates and rewards “active, independent, self-directed learning” for students to gather and assess data rigorously and critically.

This paper presents a quantitative method for automatic identification of human pulse signals. The idea is to start with the extraction of characteristic parameters and then to construct the recognition model based on Bayesian networks. To identify depth, frequency and rhythm, several parameters are proposed. To distinguish the strength and shape, which cannot be represented by one or several parameters and are hard to recognize, the main time-domain feature parameters are computed based on the feature points of the pulse signal. Then the extracted parameters are taken as the input and five models for automatic pulse signal identification are constructed based on Bayesian networks. Experimental results demonstrate that the method is feasible and effective in recognizing depth, frequency, rhythm, strength and shape of pulse signals, which can be expected to facilitate the modernization of pulse diagnosis.

This paper analyses a key problem in the quantification of pulse diagnosis. Due to the subjectivity and fuzziness of pulse diagnosis, quantitative methods are needed. To extract the parameters of pulse signals, the prerequisite is to detect the corners of pulse signals correctly. Up to now, the pulse parameters are mostly acquired by marking the pulse corners manually, which is an obstacle to modernize pulse diagnosis. Therefore, a new automatic parameters extraction approach for pulse signals using wavelet transform is presented. The results testified that the method we proposed is feasible and effective and can detect corners of pulse signals accurately, which can be expected to facilitate the modernization of pulse diagnosis.

An efficient, convenient Cu-catalyzed formation of chromeno[4,3-c]pyrazol-4(1H)-ones is reported. In this atom economic process, readily available 3-acylcoumarin hydrazone is oxidative cyclized by direct C–N bond formation. Air has been successfully used as an oxidant, which has important economic and environmental advantages. A broad scope of 3-acylcoumarin hydrazones can be utilized in this process.

// Fang Wei 1, 6, * , Xiao-Xiang Rong 3, * , Rao-Ying Xie 1, * , Li-Ting Jia 5 , Hui-Yan Wang 1 , Yu-Juan Qin 1 , Lin Chen 1 , Hong-Fen Shen 1 , Xiao-Lin Lin 1 , Jie Yang 1 , Sheng Yang 1 , Wei-Chao Hao 1 , Yan Chen 1 , Sheng-Jun Xiao 5 , Hui-Rong Zhou 5 , Tao-Yan Lin 1 , Yu-Shuang Chen 1 , Yan Sun 4 , Kai-Tai Yao 1 , Dong Xiao 1, 2 1 Cancer Research Institute, Southern Medical University, Guangzhou 510515, China 2 Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China 3 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 4 Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA 5 Department of Pathology, Guilin Medical College, Guilin 541001, China 6 Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China * These authors have contributed equally to this work Correspondence to: Dong Xiao, e-mail: Xiao_d@hotmail.com Kai-Tai Yao, e-mail: yao.kaitai@hotmail.com Keywords: nasopharyngeal carcinoma, cytokine-induced killer cells, cancer stem cells, promoter-reporter gene strategy, time-lapse imaging Received: May 27, 2015 Accepted: September 04, 2015 Published: September 16, 2015 ABSTRACT Cancer stem cells (CSCs) are considered to be the root cause for cancer treatment failure. Thus, there remains an urgent need for more potent and safer therapies against CSCs for curing cancer. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against putative CSCs of nasopharyngeal carcinoma (NPC) was fully evaluated in vitro and in vivo . To visualize putative CSCs in vitro by fluorescence imaging, and image and quantify putative CSCs in tumor xenograft-bearing mice by in vivo bioluminescence imaging, NPC cells were engineered with CSC detector vector encoding GFP and luciferase (Luc) under control of Nanog promoter. Our study reported in vitro intense tumor-killing activity of CIK cells against putative CSCs of NPC, as revealed by percentage analysis of side population cells, tumorsphere formation assay and Nanog-promoter-GFP-Luc reporter gene strategy plus time-lapse recording. Additionally, time-lapse imaging firstly illustrated that GFP-labeled or PKH26-labeled putative CSCs or tumorspheres were usually attacked simultaneously by many CIK cells and finally killed by CIK cells, suggesting the necessity of achieving sufficient effector-to-target ratios. We firstly confirmed that NKG2D blockade by anti-NKG2D antibody significantly but partially abrogated CIK cell-mediated cytolysis against putative CSCs. More importantly, intravenous infusion of CIK cells significantly delayed tumor growth in NOD/SCID mice, accompanied by a remarkable reduction in putative CSC number monitored by whole-body bioluminescence imaging. Taken together, our findings suggest that CIK cells demonstrate the intense tumor-killing activity against putative CSCs of NPC, at least in part, by NKG2D-ligands recognition. These results indicate that CIK cell-based therapeutic strategy against CSCs presents a promising and safe approach for cancer treatment.

Vascular diseases are the most prevalent diseases worldwide. This study intended to analyze peripheral blood miRNA levels and their correlation with NT-pro-BNP and cTN-I in patients with atherosclerosis or pre-atherosclerotic conditions to build a dynamic correlation between vascular diseases and their biomarkers. Serum NT-pro-BNP and cTN-I levels were measured by their respective ELISA kits. The miRNA levels were assayed by quantitative PCR. Unique miRNA signatures were identified for both atherosclerosis and pre-atherosclerosis. The levels of miR-92a, 126, 130a, 222, and 370 levels were decreased in the peripheral blood of pre-atherosclerotic subjects. In atherosclerosis, miR-21, 122, 130a, and 211 were significantly increased whereas miR-92a, 126, and 222 were markedly decreased. Serum levels of NT-pro-BNP and cTN-I correlated with each other and increased with the progression of atherosclerosis. Moreover, the levels of cTN-I and NT-pro-BNP were positively correlated with miR-21 and negatively correlated with miR-126. Integrating specific pattern of miRNA levels with NT-pro-BNP and/or cardiac troponin may improve the diagnosis of cardiovascular diseases.

A series of chromeno[4,3-d]pyrazolo[3,4-b]pyridin-6(3H)-one derivatives was easily and efficiently synthesized by the reaction of 2H-chromen-2-ones with pyrazol-5-amines catalyzed by CuCl2⋅2H2O in ethanol. This protocol has the advantages of mild reaction conditions, easy work-up, and high yields. These compounds were showed to have high fluorescence quantum yields, which mentioned their value as luminescence or fluorescence probe.

Objective: To explore the clinical value of prenatal screening for fetal-free DNA in maternal blood. Methods: A total of 10,275 maternal blood samples were collected from October 2012 to May 2016 at the prenatal diagnosis center of Changzhou Woman and Children Health Hospital. Results: Among 10,275 pregnant women accepted noninvasive prenatal testing (NIPT), 9 cases could not get the results after collected the blood second times. The rate of NIPT failure was 0.09%. Seventy-two cases got the NIPT positive results of trisomy 21/trisomy 18/trisomy 13, and the detection rate, specificity, positive predictive value (PPV), and false positive rate were 98.59%, 99.99%, 97.22%, and 0.02%. The top-3 indications of the study were advanced age women (34.90%), high risk (25.22%), and intermediate risk (19.56%). They all had the satisfactory results of NIPT. Fifty-seven pregnant women had the high risk of fetal sex chromosomal aneuploidies (SCA). After informed consent, 33 cases accepted prenatal diagnosis. Eighteen cases were confirmed as sex chromosome aneuploidies. The PPV was 54.54%. Compared with other SCA, the PPV of Turner syndrome was lower. One case was false negative after followed up. Conclusions: NIPT showed a broad application prospects for prenatal screening and diagnosis of fetal chromosomal diseases. We should deepen mining and analyzing the clinical data, and explore the use of NIPT more reasonably from the perspective of evidence-based medicine.

Overexpression of the transcriptional factor Hes1 (hairy and enhancer of split-1) has been observed in numerous cancers, but the precise roles of Hes1 in epithelial-mesenchymal transition (EMT), cancer invasion and metastasis remain unknown. Our current study firstly revealed that Hes1 upregulation in a cohort of human nasopharyngeal carcinoma (NPC) biopsies is significantly associated with the EMT, invasive and metastatic phenotypes of cancer. In the present study, we found that Hes1 overexpression triggered EMT-like cellular marker alterations of NPC cells, whereas knockdown of Hes1 through shRNA reversed the EMT-like phenotypes, as strongly supported by Hes1-mediated EMT in NPC clinical specimens described above. Gain-of-function and loss-of-function experiments demonstrated that Hes1 promoted the migration and invasion of NPC cells in vitro. In addition, exogenous expression of Hes1 significantly enhanced the metastatic ability of NPC cells in vivo. Chromatin immunoprecipitation (ChIP) assays showed that Hes1 inhibited PTEN expression in NPC cells through binding to PTEN promoter region. Increased Hes1 expression and decreased PTEN expression were also observed in a cohort of NPC biopsies. Additional studies demonstrated that Hes1-induced EMT-like molecular changes and increased motility and invasion of NPC cells were mediated by PTEN. Taken together, our results suggest, for what we believe is the first time, that Hes1 plays an important role in the invasion and metastasis of NPC through inhibiting PTEN expression to trigger EMT-like phenotypes.