Preparation of a Tetra-Imidazolium Salt and Sensing for p-Dinitrobenzene.

A macrocyclic tetra-imidazolium salt (2) based on quinoxaline was prepared and characterized. The recognition of 2 to nitro compounds was investigated by fluorescence spectroscopy, 1H NMR titrations, MS, IR spectroscopy, and UV/vis spectroscopy. The results displayed that 2 was able to effectively differentiate p-dinitrobenzene from other nitro compounds via the fluorescence method.

An ion mobility-enabled and high-efficiency hybrid scan approach in combination with ultra-high performance liquid chromatography enabling the comprehensive characterization of the multicomponents from Carthamus tinctorius.

Liquid chromatography/mass spectrometry (LC/MS) is extensively applied for the untargeted/targeted analyses of the herbal components, utilizing data-dependent acquisition (DDA) or data-independent acquisition (DIA) to record the fragmentation information useful for the structural elucidation. A new trend recently has emerged by integrating DDA and DIA to render the hybrid scan, which, unfortunately, has rarely been reported. Herein, by using the Vion™ ion-mobility quadrupole time-of-flight mass spectrometer, a hybrid scan strategy (HDMSE-HDDDA) was presented and validated by the untargeted characterization of the multicomponents from Carthamus tinctorius (safflower), in combination with reversed-phase ultra-high performance liquid chromatography (RP-UHPLC). Good chromatographic separation was achieved on an HSS T3 column within 26 min, while HDMSE-MS/MS was used to acquire the collision-induced dissociation MS2 data in the negative mode. Automatic workflows (e.g., data correction, precursors/product ions matching, and peak annotation) were well established on UNIFI™ (incorporating an in-house library recording 261 known compounds) to process the obtained MS2 data. Compared with single DDA or DIA, the hybrid approach of HDMSE-HDDDA better balanced between the coverage and reliability, led to high-definition MS spectra, offered useful collision cross section (CCS) information, and showed satisfactory identification performance comparable to MSE. A total of 141 components (involving 41 quinochalcones, 66 flavanols/flavones, 11 flavanones, 6 organic acids, 1 polyacetylene, and 16 others) were characterized from safflower. Moreover, CCS prediction could assist isomers characterization, to some extent. Conclusively, this hybrid scan approach enables a dimension-enhanced MS data acquisition strategy providing the complementary structural information, which more suits the chemical characterization of complex samples.

Repurposing of a monoamine oxidase A inhibitor­heptamethine carbocyanine dye conjugate for paclitaxel­resistant non­small cell lung cancer.

Non­small cell lung cancer (NSCLC) remains an intractable disease, which is primarily due to tumor metastasis and the acquisition of resistance to chemotherapy. Therefore, there is an urgent need for novel therapeutics to overcome these obstacles. It was recently demonstrated that upregulated expression of monoamine oxidase A (MAOA) contributes to the progression of NSCLC. G10, a tumor­targeting representative conjugate of heptamethine carbocyanine dye and an inhibitor of MAOA, was shown to exert potent cytotoxic effects, comparable to those of doxorubicin, against prostate cancer cell lines, as well as moderate MAOA inhibitory activity. The research described herein aimed to extend our previous study on the antitumor function of G10 in NSCLC in vitro and in vivo, and to elucidate the mechanisms through which G10 exerts its antineoplastic effects. G10 markedly inhibited the proliferation of paclitaxel­resistant NSCLC cells (H460/PTX) and reduced tumor cell migration and invasion. Gene expression profiling of paclitaxel­resistant NSCLC cells following treatment with G10 demonstrated that the expression of genes associated with the extracellular matrix was significantly affected, particularly the metastasis­related genes matrix metallopeptidase (MMP)2, MMP14 and COL6A, which exhibited notably reduced expression. Additionally, the results also demonstrated that MAOA­related pathways, including AKT and hypoxia­inducible factor­1α, were also inhibited by G10 treatment and, subsequently, the downstream molecules of these pathways, such as p21, MMP2 and vascular endothelial growth factor, were also downregulated, highlighting a possible mechanism through which G10 suppresses tumor cell migration, invasion and proliferation. Importantly, in mouse NSCLC xenografts, combined treatment with G10 and paclitaxel resulted in pronounced inhibition of tumor growth. Taken together, the results of the present study highlight the potential of G10 as a novel therapeutic targeting MAOA in paclitaxel­resistant NSCLC.

Comparisons of Functional Properties of Polysaccharides from Nostoc flagelliforme under Three Culture Conditions.

Nostoc flagelliforme is an edible cyanobacterium with excellent food and herbal values. It has been used as food in China for more than 2000 years. Many studies have been focused on improving the yield and bioactivity of Nostoc flagelliforme polysaccharides although these have ignored the functional properties. In this study, we extracted and purified three polysaccharides (WL-CPS, NaCl-CPS and Glu-CPS) from Nostoc flagelliforme under normal, salt stress and mixotrophic culture conditions, respectively, in order to change the physicochemical properties of polysaccharides with the aim of obtaining better functional properties. Both salt stress and mixotrophic culture conditions increased the specific yield of polysaccharides. Their functional properties were comparatively investigated and the results showed that NaCl-CPS exhibited the highest emulsification activity and flocculation capability, which was also higher than that of some commercial products. In contrast, Glu-CPS exhibited the highest water and oil holding capacities, foaming property, intrinsic viscosity and bile acids binding capacity. Our results indicated that both NaCl-CPS and Glu-CPS could be considered to be functional polysaccharides according to their respective characteristics, which have great potential in numerous applications, such as food, pharmaceutical, cosmetic, chemical and mineral industries. These findings also demonstrated the potential application of the proper regulation of culture conditions in the development of polysaccharides with desired functional properties.

ROS Is a Factor Regulating the Increased Polysaccharide Production by Light Quality in the Edible Cyanobacterium Nostoc flagelliforme.

To explore the regulatory factor of light quality affecting exopolysaccharide (EPS) production, transcriptome analysis of Nostoc flagelliforme cells exposed to red light (R), blue light (B), and mixed light (B/R = 15:7) (BR) with white fluorescent light as control was performed. The differentially expressed genes mainly enriched in carbohydrate metabolism and energy metabolism. Significant enrichment in the oxidation-reduction process and energy metabolism indicated that intracellular redox homeostasis was disrupted. An assay of reactive oxygen species (ROS) and malondialdehyde contents demonstrated light quality induced oxidative stress. To illustrate the relationship between ROS level and EPS accumulation, the effects of the exogenous addition of ROS scavenger N-acetyl cysteine and inducer H2O2 on the oxidation-reduction level and EPS production were compared. The results revealed that light quality regulated EPS biosynthesis via the intracellular ROS level directly other than oxidative stress. Understanding such relationships might provide guidance for efficient EPS production to regulate the intracellular redox level.

Comparative proteomic analysis of Nostoc flagelliforme reveals the difference in adaptive mechanism in response to different ultraviolet-B radiation treatments.

Nostoc flagelliforme is a pioneer organism in the desert and highly resistant to ultraviolet B (UV-B) radiation, while the involved adaptive mechanism has not been fully explored yet. To elucidate the responsive mechanism, two doses of UV-B radiation (low: 1 W/m2 and high: 5 W/m2) were irradiated for 6 h and 48 h, respectively, and their effects on global metabolism in N. flagelliforme were comprehensively investigated. In this study, we used iTRAQ-based proteomic approach to explore the proteomes of N. flagelliforme, and 151, 172, 124 and 148 differentially expressed proteins were identified under low and high UV-B doses for 6 h and 48 h, respectively. Functional classification analysis showed these proteins were mainly involved in photosynthesis, amino acid metabolism, antioxidant activity and carbohydrate metabolism. Further analysis revealed that UV-B imposed restrictions on primary metabolism including photosynthesis, Calvin cycle, and amino acid metabolism, and cells started defense mechanism through repair of DNA and protein damage, increasing antioxidant activity, and accumulating extracellular polysaccharides to minimize the damage. Moreover, high UV-B dose imposed more severe restrictions and activated stronger defense mechanism compared with low dose. The results would improve the understanding of molecular mechanisms of UV-B-stress adaption in N. flagelliforme.

Effect of culture conditions on the physicochemical properties and antioxidant activities of polysaccharides from Nostoc flagelliforme.

Three polysaccharides (WL-CPS-1, NaCl-CPS-1 and Glu-CPS-1) were extracted and purified from Nostoc flagelliforme under normal, salt stress and mixotrophic culture conditions respectively. Their physicochemical properties and antioxidant activities were investigated. WL-CPS-1, NaCl-CPS-1 and Glu-CPS-1 chemical composition differed in sugar and uronic acid contents, and they were composed of nine constituent monosaccharides and one uronic acid with different ratios, with the average molecular weights of 1.02 × 103, 1.12 × 103 and 1.33 × 103 kDa, respectively. They presented similar fourier transform infrared spectra, but different surface morphology, chain length and branching. Antioxidant assay showed that they all exhibited strong scavenging activity on ABTS+ and hydroxyl radicals and moderate activity on DPPH radical. Glu-CPS-1 exhibited the highest antioxidant activity suggested culture conditions could regulate the bioactivity through influencing the structure and properties. These findings demonstrated the potential application of proper regulation of culture conditions in the development of polysaccharides with high antioxidant activity.

The physiological responses of terrestrial cyanobacterium Nostoc flagelliforme to different intensities of ultraviolet-B radiation.

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.

Comparative research on tillable properties of diatomite-improved soils in the Yangtze River Delta region, China.

To improve soil texture and structure, techniques associated with physical, biological or chemical aspects are generally adopted, among which diatomite is an important soil conditioner. However, few studies have been conducted to investigate the physical, hydraulic and tillage performance of diatomite-improved soils. Consistency limits and compaction properties were investigated in this study, and several performance indicators were compared, such as the liquid limit, plastic limit and compactability, of silt, silt loam and silty-clay loam soils to which diatomite was added at volumetric ratios of 0%, 10%, 20%, and 30%. The results showed that diatomite significantly (p<0.05) improved the consistency limits, with the most preferred effects in the silt soil. The liquid limits were increased by 53.9%, 27.3%, and 14.7%, in the silt, silt loam and silty-clay loam soils, respectively, when the volumetric ratio was 30%. While diatomite lowered the maximum dry bulk density (MBD) of the classified soils, the optimum moisture content (OMC) was increased overall. The trend was consistent with the proportion of diatomite, and MBD decreased by 8.7%, 10.3%, and 13.2% in the silt, silt loam and silty-clay loam soils when 30% diatomite was mixed, whereas OMC increased by 28.7%, 22.4%, and 25.3%, respectively. Additionally, aggregate stability was negatively correlated with MBD but positively correlated with OMC. Diatomite exerts positive effects on soil mechanical strength, suggesting that soils from sludge farms are more tillable with a larger stabilized and workable matrix.

Association of E-selectin gene polymorphisms with ischemic stroke in a Chinese Han population.

The E-selectin gene, a member of the selectin superfamily of adhesion molecules, plays an important role in the pathogenesis of thrombovascular diseases. The present study was designed to investigate the potential relationship between E-selectin gene polymorphisms and ischemic stroke in a Chinese Han population. Three hundred fourteen ischemic stroke patients and 389 unrelated healthy controls were recruited for the study. Three single-nucleotide polymorphisms (SNPs)-rs1805193(G98T), rs5361(A561C), and rs5355(C1839T)-in the exon region of the E-selectin gene, were genotyped using a Multiplex SNaPshot sequencing assay. The data showed that the genotype and allele frequencies of G98T and C1839T SNP were similar in both ischemic stroke patients and the controls. In contrast, the frequency of both the AC genotype and the C allele of A561C was significantly higher in ischemic stroke patients than in healthy controls (P = 0.001, P < 0.001, respectively). After adjusting for other risk factors (such as hypertension, diabetes, tobacco smoking, and alcohol consumption), the E-selectin gene AC genotype and C allele of A561C were still associated with a risk of ischemic stroke (odds ratio [OR] = 2.73, 95% confidence interval (CI): 1.29-5.76, P = 0.008; OR = 2.80, 95% CI: 1.58-4.94, P < 0.001, respectively). Our current study demonstrates that the E-selectin SNP A561C is associated with increased risk for the development of ischemic stroke in this subset of the Han Chinese population.