Hydroxyl porous aromatic frameworks for efficient adsorption of organic micropollutants in water

Environmental pollution is an important issue in sustainable human development. People give great importance to environmental protection, especially with regards to increasingly scarce water resources. Water pollution is becoming more and more serious due to the existence of organic micropollutants. As a platform with good stability, porous aromatic frameworks (PAFs) have been widely studied. Because of their high surface area and thermal stability, they are considered to be a good sewage treatment agent. However, the aromatic nature of PAFs makes their skeletons mostly hydrophobic. This characteristic of PAFs seriously affects their diffusion rate in water as an adsorbent, resulting in a low adsorption rate. In this work, we synthesized a series of hydroxyl functionalized porous aromatic frameworks (PAF-80, PAF-81, and PAF-82) via the Sonogashira–Hagihara cross-coupling reaction, which created polar motifs on the hydrophobic surfaces, and carried out adsorption tests on typical organic micropollutants in water such as bisphenol A (BPA), 2-naphthol (2-NO) and p-chloroxylenol (PCMX). Among the three PAFs, PAF-82 exhibited the highest BET surface area, polar active sites, and a high degree of conjugation, which led to the best adsorption performance compared to that of PAF-80 and PAF-81. The Langmuir adsorption capacity of PAF-82 for BPA, 2-NO, and PCMX is 689 mg g⁻¹, 431 mg g⁻¹, and 480 mg g⁻¹, respectively, which surpasses most previously reported adsorbents. In addition, after 5 cycles of regeneration, it still maintained a high removal rate for pollutants. The obtained results reveal that micropollutant adsorption in water is not controlled by a single factor, but is the result of a synergy of multiple factors, including specific surface area, polar functional groups, pore size distribution, and skeleton conjugation. Our study has revealed the great potential of hydroxyl PAFs for efficient adsorption of organic micropollutants in water.

A series of hydroxyl functionalized PAF materials (PAF-80, PAF-81, and PAF-82) were synthesized, which create polar channels to the hydrophobic surfaces and explored as efficient adsorption of organic micropollutants in water.     

Nonparametric Tests of Associations with Disease Based on U‐Statistics

In case‐control studies, association analysis was designed to test whether genetic variants were associated with human diseases. To evaluate the association, analysing one genetic marker at a time suffered from weak power, because of the correction for multiple testing and possibly small genetic effects. An alternative strategy was to test simultaneous effects of multiple markers, which was believed to be more powerful. However, when the number of markers under investigation was large, they would be subjected to weak power as well, because of the greater degrees of freedom. To conquer these limitations in case‐control studies, we proposed a novel method that could test joint association of several loci (i.e. haplotype), with only a single degree of freedom. In this research, we developed a nonparametric approach, which was based on U‐statistics. We also introduced a new kernel for U‐statistic, which could combine the haplotype structure information, and was expected to enhance the power. Simulations indicated that our proposed approach offered merits in identifying the associations between diseases and haplotypes. Application of our method to a study of candidate genes for internalising disorder illustrated its virtue in utility and interpretation, and provided an excellent result in detecting the associations.     

Resistance to obesity by repression of VEGF gene expression through induction of brown-like adipocyte differentiation

Adipose tissues are classified into white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is responsible for energy storage, and malfunction is associated with obesity. BAT, on the contrary, consumes fat to generate heat through uncoupling mitochondrial respiration and is important in body weight control. Vascular endothelial growth factor (VEGF)-A is the founding member of the VEGF family and has been found highly expressed in adipose tissue. A genetic mouse model of an inducible VEGF (VEGF-A) repression system was used to study VEGF-regulated energy metabolism in WAT. VEGF-repressed mice demonstrated lower food efficiency, lower body weight, and resistance to high-fat diet-induced obesity. Repression of VEGF expression caused morphological and molecular changes in adipose tissues. VEGF repression induced brown-like adipocyte development in WAT, up-regulation of BAT-specific genes including PRDM16, GATA-1, BMP-7, CIDEA, and UCP-1 and down-regulation of leptin, a WAT-specific gene. VEGF repression up-regulated expression of VEGF-B and its downstream fatty acid transport proteins. Relative levels of VEGF/VEGF-B may be important switches in energy metabolism and of pharmaceutical significances.     

Scenario simulation-based assessment of trip difficulty for urban residents under rainstorm waterlogging

In this study, an experiment was performed to assess the trip difficulty for urban residents of different age groups walking in various depths of water, and the data were corroborated with the real urban rainstorm waterlogging scenarios in downtown (Daoli district) Ha-Erbin (China). Mathematical models of urban rainstorm waterlogging were constructed using scenario simulation methods, aided by the GIS spatial analysis technology and hydrodynamic analysis of the waterway systems in the study area. Then these models were used to evaluate the impact of waterlogging on the safety of residents walking in the affected area. Results are summarized as: (1) for an urban rainstorm waterlogging scenario reoccurring once every 10 years, three grid regions would have waterlogging above 0.5 m moving at a velocity of 1.5 m/s. Under this scenario, waterlogging would accumulate on traffic roads only in small areas, affecting the safety and mobility of residents walking in the neighborhood; (2) for an urban rainstorm waterlogging scenario reoccurring once every 20 years, 13 grids experienced the same waterlogging situation affecting a larger area of the city; (3) for an urban rainstorm waterlogging scenario reoccurring once every 50 years, 86 grid regions were affected (waterlogging above 0.5 m moving at 1.5 m/s), and those areas would become impassable for residents.     

Application of porous nickel-coated TiO₂ for the photocatalytic degradation of aqueous quinoline in an internal airlift loop reactor

P25 film, prepared by a facile dip-coating method without any binder, was further developed in a recirculating reactor for quinoline removal from synthetic wastewater. Macroporous foam Ni, which has an open three-dimensional network structure, was utilized as a substrate to make good use of UV rays. Field emission scanning electron microscopy and X-ray diffraction analysis showed that the coated/calcinated P25 films consisted of two crystal phases, and had a number of uniform microcracks on the surface. The effects of initial quinoline concentration, light intensity, reaction temperature, aeration, and initial pH were studied. Increased reaction time, light intensity, environmental temperature, and gas aeration were found to significantly improve the quinoline removal efficiency. The aeration effect of oxygen dependency on the quinoline degradation had the trend pure oxygen > air > no gas > pure nitrogen with free O?. The solution pH crucially affected quinoline photodegradation; the high electrostatic adsorption of quinoline molecules on the TiO? surface was strongly pH dependent. 2-Pyridine-carboxaldehyde, 3-pyridinecarboxaldehyde, and 2(1H)-quinolinone were identified as the major intermediates of quinoline degradation. Based on these intermediates, a primary degradation mechanism was proposed. This reusable P25 film benefits the photodegradation of water contaminants and has potential in other various applications.     

Par-4 activation restrains EMT-induced chemoresistance in PDAC by attenuating MDM-2

BackgroundWe recently reported prostate apoptosis response 4 (Par-4), a potential tumor suppressor protein restrains epithelial-mesenchymal transition (EMT) properties and promotes mesenchymal-epithelial transition (MET) in invasive cancer cells by repressing Twist-1 promoter activity. Here, we demonstrate that genetic as well as pharmacological modulation of Par-4 by NGD16 (a small molecule antimetastatic agent), limits EMT-induced chemoresistance in aggressive cancer cells by suppressing MDM-2, a downstream effector of Twist-1.MethodsMatrigel invasion assay, gelatin degradation assay, cell scattering assay, MTT assay and colony formation assay were used to study the proliferation and migration abilities of invasive cancer cells. Immunoblotting, immunocytochemistry, and immunoprecipitation analysis were utilized for determining protein expression and protein-protein interaction. 4T1 aggressive mouse carcinoma model was employed to evaluate tumor growth and lung metastasis.ResultsTreatment of gemcitabine (nucleoside analogue anticancer agent) to pancreatic cancer (Panc-1, MiaPaca-2) and breast cancer (MDA-MB-231) cells amplified MDM-2 expression along with increase in EMT properties. Conversely, NGD16 boosted expression of tumor suppressor Par-4 and inhibited invasion and migration abilities of these cells. Moreover, induction of Par-4 effectively diminished MDM-2 along with pro-EMT markers, whereas, augmented the expression of epithelial markers. Furthermore, siRNA-mediated silencing of Par-4 divulged that NGD16 exerts its EMT inhibitory effects in a Par-4-dependent manner. Mechanistically, Par-4 activation provokes p53 by disrupting MDM-2-p53 interaction, which restored epithelial characteristics in cancer cells. Additionally, partial knockdown of MDM-2 through siRNA pronounced the anti-proliferative and anti-invasive effects of NGD16. Finally, NGD16 efficiently inhibited tumor growth and lung metastasis in mouse mammary carcinoma model without showing any undesirable effects.ConclusionOur findings unveil Par-4 as a key therapeutic target and NGD16 (the pharmacological modulator of Par-4) are potential tools to suppress EMT and associated chemoresistance, which could be exploited clinically for the treatment of aggressive cancers.     

Silver-catalyzed regioselective deuteration of (hetero)arenes and α-deuteration of 2-alkyl azaarenes

A simple silver-catalyzed regioselective deuteration of (hetero)arenes and α-deuteration of 2-alkyl azaarenes has been described. This strategy provides an efficient and practical avenue to access various deuterated electron-rich arenes, azaarenes and α-deuterated 2-alkyl azaarenes with good to excellent deuterium incorporation utilizing D₂O as the source of deuterium atoms.

A practical silver-catalyzed regioselective deuteration of (hetero)arenes and α-deuteration of 2-alkyl azaarenes utilizing D₂O as a deuterium source has been developed.

Deuterium-labelled organic compounds are of great interest and importance, as they are widely used as internal standards in analytical chemistry,¹ tools for elucidation of reaction mechanisms,² metabolic or pharmacokinetic probes,³ and as biologically active compounds and pharmaceuticals.⁴ Indeed, the first deuterated drug, deutetrabenazine, which is recognized as a different orphan drug for the treatment of chorea versus tetrabenazine, was approved by the US Food and Drug Administration in April 2017. As a result, the development of efficient and selective routes for the synthesis of deuterium labeled organic compounds is a subject of increasing interest. Among possible approaches to incorporate deuterium atoms into an organic molecule,⁵ the H/D exchange reaction, which enables the direct deuterium labelling of the desired target molecule without the need to prefunctionalize the starting materials, represents the most straightforward and atom-efficient method. In recent years, extensive studies on H/D exchange reactions of aromatic compounds have been reported, including acid/base promoted pH-dependent H/D exchange reactions of electronically activated aromatic compounds⁶ (Scheme 1a) and transition metal catalyzed site-selective H/D exchange reactions⁷ (Scheme 1b). Among these, transition-metal-catalyzed reactions have gained significant momentum because these catalysts can control the site selectivity of H/D exchange reactions. However, the required ligands, the introduction of directing groups and/or the complexity of catalyst synthesis may not be readily accessible or economically viable. Therefore, there remains room to develop a simple, cost efficient and universal deuteration strategy with broad substrate scope, especially in view of the growing demand for deuterium-labelled compounds in synthetic chemistry and pharmaceutical industry.Open in a separate windowScheme 1Selective H/D exchange reactions.In past decades, silver has demonstrated their high efficiency as special mild Lewis acids, becoming catalysts of first choice for many types of catalytic reactions generally performed under mild reaction conditions and through experimentally simple procedures.⁸ However, despite considerable progress, silver-catalyzed selective H/D exchange reaction has remained much less explored to date.⁹ Quite recently, Huang reported an efficient Ag₂CO₃-catalyzed H/D exchange of five-membered heteroarenes using D₂O as deuterium source at ambient temperature, but external base such as 1 equiv. of K₂CO₃ and a phosphine ligand were still needed.^9b We here developed a practical and selective silver-catalyzed deuteration of (hetero)arenes and α-deuteration of 2-alkyl azaarenes utilizing D₂O as the source of deuterium atom under mild neutral conditions that does not require any other additives (Scheme 1c). This protocol represents a practical and efficient method of silver-catalyzed regioselective H/D exchange reaction under mild neutral conditions, efficiently affording a wide range of deuterated electron-rich arenes, azaarenes and α-deuterated 2-alkyl azaarenes through experimentally simple procedures.Initially, we began our studies by examining the model deuteration of 1,2,3,4-tetrahydroquinoline (1a) with D₂O using various commercially available silver salts as the catalyst. To our delight, 94% deuterium incorporation was achieved in the ortho- and para-positions by using 10 mol% AgOTf in CDCl₃ at 90 °C (9a Control experiment suggests that AgOTf is necessary in this reaction (10,11Optimization of conditions for the silver-catalyzed deuteration of 1a^a

25-methoxyl-dammarane-3β, 12β, 20-triol and artemisinin synergistically inhibit MDA-MB-231 cell proliferation through downregulation of testes-specific protease 50 (TSP50) expression

Tumor Biology - While the incidence of cancer continues to increase, the current therapeutic options remain imperfect. Therefore, there is an urgent need to discover new targeted anti-cancer...