Design, Synthesis and Characterization of Palladium-Functionalized Covalent Organic Framework and Its Application as Heterogeneous Catalysis for C-H Arylation of Azoles.

A novel triazine-based covalent organic framework (TFPT-Bz COF) has been constructed by the condensation of 2,4,6-tris(5-formyl-2-pyridinoxy)-1,3,5-triazine (TFPT) and benzidine (BZ) with deep eutectic solvent (DES) as the reaction medium. After the introduction of Pd ions through strong coordination to TFPT-Bz COF matrix, the constructed TFPT-Bz COF/Pd composite exhibited excellent catalytic activity for C-H arylation of azoles with aryl halides in 2-methyltetrahydrofuran. The protocol allows the arylation of a variety of substituted azoles with diverse aryl halides in high to excellent yield. Moreover, the TFPT-Bz COF/Pd catalyst can be recycled several times without significantly reducing its activity.

An Improved Grey Wolf Optimizer and Its Application in Robot Path Planning.

This paper discusses a hybrid grey wolf optimizer utilizing a clone selection algorithm (pGWO-CSA) to overcome the disadvantages of a standard grey wolf optimizer (GWO), such as slow convergence speed, low accuracy in the single-peak function, and easily falling into local optimum in the multi-peak function and complex problems. The modifications of the proposed pGWO-CSA could be classified into the following three aspects. Firstly, a nonlinear function is used instead of a linear function for adjusting the iterative attenuation of the convergence factor to balance exploitation and exploration automatically. Then, an optimal α wolf is designed which will not be affected by the wolves ß and δ with poor fitness in the position updating strategy; the second-best ß wolf is designed, which will be affected by the low fitness value of the δ wolf. Finally, the cloning and super-mutation of the clonal selection algorithm (CSA) are introduced into GWO to enhance the ability to jump out of the local optimum. In the experimental part, 15 benchmark functions are selected to perform the function optimization tasks to reveal the performance of pGWO-CSA further. Due to the statistical analysis of the obtained experimental data, the pGWO-CSA is superior to these classical swarm intelligence algorithms, GWO, and related variants. Furthermore, in order to verify the applicability of the algorithm, it was applied to the robot path-planning problem and obtained excellent results.

Blocking Notch signalling reverses miR-155-mediated inflammation in allergic rhinitis.

Although recent studies have shown that the Notch signalling pathway induces the production of Th2-related immune factors, the exact mechanism through which Notch signalling exacerbates allergic rhinitis (AR) remains unknown. To investigate the roles of Notch in AR, serum, nasal mucosa and spleen samples were isolated from BALB/c mice. Paraffin sections were stained with haematoxylin and eosin (H&E) or periodic acid-Schiff (PAS) to assess inflammation. Flow cytometry was performed to detect group 2 innate lymphoid cells (ILC2s) in the serum samples, and cytokine levels were measured by enzyme-linked immunosorbent assays (ELISAs). The mRNA expression levels of the Notch signalling pathway components and miR-155 were measured by quantitative real-time PCR (qRT-PCR). In addition, human nasal epithelial cells (HNEpCs) were cultured to investigate the functional consequences of Notch pathway inhibition. The findings demonstrated that symptomatology and pathology were substantially altered, and AR model mice were established. In vivo stimulation with ovalbumin (OVA) significantly increased the Th2-type immune responses and the expression of OVA-sIgE, IL-4, GATA3, NF-κB and miR-155. However, the Notch signalling pathway was significantly deteriorated in AR, and this effect was accompanied by reduced Notch1, Notch2, RBPj and Hes1 levels. These effects were abrogated by gamma-secretase inhibitor IX (DAPT) treatment, and DAPT inhibited the wound healing and proliferation of HNEpCs in a dose-dependent manner. Therefore, our results suggest that blocking the Notch pathway may alleviate miR-155-mediated inflammation via the regulation of immune homeostasis in AR.

MiR-665 Regulates Vascular Smooth Muscle Cell Senescence by Interacting With LncRNA GAS5/SDC1.

Background: Vascular aging is considered a special risk factor for cardiovascular diseases, and vascular smooth muscle cells (VSMCs) play a major role in aging-related vascular remodeling and in the pathological process of atherosclerosis. Recent research has reported that long non-coding RNA/microRNA (lncRNA/miRNA) is a critical regulator of cellular senescence. However, the role and mechanism of lncRNA GAS5/miR-665 axis in VSMC senescence remain incompletely understood. Methods: Cellular senescence was evaluated using senescence-associated ß-gal activity, the NAD+/NADH ratio, and by immunofluorescence staining of γH2AX immunofluorescence. Differentially expressed miRNAs (DEMs) were identified by miRNA microarray assays and subsequently validated by quantitative real-time PCR (qRT-PCR). A dual luciferase reporter assay was conducted to confirm the binding of lncRNA GAS5 and miR-665 as well as miR-665 and syndecan 1 (SDC1). Serum levels of miR-665, lncRNA GAS5, and SDC1 in 93 subjects were detected by qRT-PCR. The participants were subdivided into control, aging, and early vascular aging (EVA) groups, and their brachial-ankle pulse wave velocity (baPWV) was measured. Results: A total of 20 overlapping DEMs were identified in young and old VSMCs via microarray analysis. MiR-665 showed a significant alteration and, therefore, was selected for further analysis. Upregulation of miR-665 was found in aging VSMCs, and downregulation of miR-665 caused an inhibition of VSMCs senescence. Subsequently, the dual luciferase reporter assay determined the binding site of miR-665 with the 3'-UTR of lncRNA GAS5 and SDC1. Increased expression of lncRNA GAS5 expression inhibited the miR-665 level and VSMC senescence. However, as shown in rescue experiment results, either miR-665 overexpression or SDC1 knockdown significantly reversed the effects of lncRNA GAS5 on VSMC senescence. Finally, compared with that of the control group, miR-665 was highly expressed in serum samples in the aging and EVA groups, especially in the EVA groups. On the contrary, serum levels of lncRNA GAS5 and SDC1 were lower in these two groups. Collectively, in the aging and EVA groups, miR-665 expression was negatively correlated with lncRNA GAS5 and SDC1 expression. Conclusion: miR-665 inhibition functions as a vital modulator of VSMC senescence by negatively regulating SDC1, which is achieved by lncRNA GAS5 that sponges miR-665. Our findings may provide a new treatment strategy for aging-related cardiovascular diseases.

Adaptive harmony search algorithm utilizing differential evolution and opposition-based learning.

An adaptive harmony search algorithm utilizing differential evolution and opposition-based learning (AHS-DE-OBL) is proposed to overcome the drawbacks of the harmony search (HS) algorithm, such as its low fine-tuning ability, slow convergence speed, and easily falling into a local optimum. In AHS-DE-OBL, three main innovative strategies are adopted. First, inspired by the differential evolution algorithm, the differential harmonies in the population are used to randomly perturb individuals to improve the fine-tuning ability. Then, the search domain is adaptively adjusted to accelerate the algorithm convergence. Finally, an opposition-based learning strategy is introduced to prevent the algorithm from falling into a local optimum. The experimental results show that the proposed algorithm has a better global search ability and faster convergence speed than other selected improved harmony search algorithms and selected metaheuristic approaches.

miR-5701 promoted apoptosis of clear cell renal cell carcinoma cells by targeting phosphodiesterase-1B.

Increasing evidence has demonstrated that microRNAs play critical roles in malignant biological behaviors, including cancerogenesis, cancer progression and metastasis, through the regulation of target genes expression. As miR-5701 has recently been identified to play roles as tumor suppressor miRNA in the development of some kinds of cancers, in this study we sought to investigate the role of miR-5701 in clear cell renal cell carcinoma (ccRCC). Colony formation, cell apoptosis and proliferation assays were employed, and the results showed that miR-5701 inhibited proliferation and promoted apoptosis of ccRCC cells. Western blotting and dual-luciferase reporter assays were used to confirm that PDE1B is a new direct target of miR-5701. Furthermore, overexpression of PDE1B attenuated the effects of miR-5701, indicating that miR-5701 inhibited proliferation and promoted apoptosis of ccRCC cells via targeting PDE1B. Taken together, the data presented here indicate that t miR-5701 is a tumor suppressor in ccRCC and PDE1B is a new target of miR-5701.

FOXN3 suppresses the growth and invasion of papillary thyroid cancer through the inactivation of Wnt/ß-catenin pathway.

Forkhead box N3 (FOXN3) is a subtype of FOX family that has been demonstrated to be implicated in several cancers. However, the role of FOXN3 in papillary thyroid carcinoma (PTC) and its mechanisms have not yet been investigated. Our results showed that FOXN3 was markedly down regulated in PTC tissues and cell lines. Overexpression of FOXN3 suppressed the proliferation, colony formation, migration, and invasion in PTC cells. Overexpression of FOXN3 also prevented EMT process in PTC cells, as shown by the increased E-cadherin expression level and decreased expression levels of N-cadherin and vimentin. In addition, overexpression of FOXN3 inhibited tumor growth of PTC in vivo. Furthermore, overexpression of FOXN3 caused significant decreases in expression levels of ß-catenin, c-Myc, and cyclin D1. Additionally, activation of Wnt/ß-catenin pathway reversed the effects of FOXN3 on PTC cells. In conclusion, these findings indicated that FOXN3 exerted a tumor suppressive activity in PTC, which was mediated by Wnt/ß-catenin pathway.

Bioavailability and soil-to-crop transfer of heavy metals in farmland soils: A case study in the Pearl River Delta, South China.

Soil-bound heavy metals are of great concern for human health due to the potential exposure via food chain transfer. In the present study, the occurrence, the bioavailability and the soil-to-crop transfer of heavy metals in farmland soils were investigated based on data from two agricultural areas, i.e. Sihui and Shunde in South China. Six heavy metals (As, Cu, Hg, Mn, Ni and Pb) were quantified in the farmland soils. The mean single pollution level indices (PI) were all lower than 1 except for Hg in soils from Shunde (PI = 1.51 ±â€¯0.46), suggesting the farmland soils were within clean and slightly polluted by heavy metals. As, Cu, Ni and Pb were found to be mostly present in the non-bioavailable form. The majority of Hg was considered potentially bioavailable, and Mn was found to be largely bioavailable. Soil pH was an important factor influencing bioavailability of soil-bound heavy metals. The concentrations of heavy metals in vegetables from Sihui and Shunde were within the food hygiene standards, while the rice grain from Sihui was polluted by Pb (PI = 10.3 ±â€¯23.4). Total soil concentrations of heavy metals were not correlated to their corresponding crop concentrations, instead, significant correlations were observed for bioavailable concentrations in soil. The results supported the notion that the bioavailability of the investigated heavy metals in the soil was largely responsible for their crop uptake. The soil-to-crop transfer factors based on bioavailable concentrations suggested that Cu, As and Hg in soils of the study area had greater tendency to be accumulated in the vegetables than other heavy metals, calling for further human health assessment by consuming the contaminated crops.

Preventive and therapeutic effects of sodium bicarbonate on melamine-induced bladder stones in mice.

The actual preventive and therapeutic effects of alkalinizing urine on melamine-induced bladder stones (cystolith) are not completely known. Using an ideal model, two experiments were conducted in Balb/c mice. The mice were fed a normal diet in controls and a melamine diet in the other groups. The first day was set as experiment-day 1. In "Experiment 1", either low-/mid-/high-dose sodium bicarbonate (SB) or sterile water was administered by intragastric perfusion (once daily) to the mice for 14 days. Relative to the model group, the mean pH of the urine in the SB groups was significantly elevated at 3 h after SB administration, with a significant decrease in cystolith incidence on experiment-day 14. In "Experiment 2", on experiment-day 12, the melamine diet was replaced by a normal diet in 4 groups with melamine withdrawal (MW). Meanwhile, either mid-/high-dose SB or sterile water was administered by intragastric perfusion (once) to the mice in the corresponding groups. On experiment-day 12, after an additional 8 h, the cystolith incidence was significantly reduced in the high-SB, MW + mid-SB and MW + high-SB groups than in the model group. In conclusion, low urinary pH is one of the main determinants of the formation of melamine-associated stones, urinary alkalinization can be achieved by a proper dose of oral SB, and SB acts to prevent and treat melamine-induced cystoliths in mice.

Meglumine: A novel and efficient catalyst for one-pot, three-component combinatorial synthesis of functionalized 2-amino-4H-pyrans.

An efficient one-pot synthesis of functionalized 2-amino-4H-pyrans by a meglumine-catalyzed three-component reaction has been developed. A broad range of substrates including aromatic and heteroaromatic aldehydes, isatin derivatives, and acenaphthenequinone are condensed with enolizable C-H activated compounds and alkylmalonates to give the desired products in high to excellent yields. This methodology provides an alternative approach for rapid access to construct a diversity-oriented library of 4H-pyrans.

Conspicuity of breast lesions at different b values on diffusion-weighted imaging.

BACKGROUND: Diffusion-weighted (DW) imaging has shown potential to differentiate between malignant and benign breast lesions. However, different b values have been used with varied sensitivity and specificity. This study aims to prospectively evaluate the influence of b value on the detection and assessment of breast lesions. METHODS: Institutional review board approval and informed patient consent were obtained. Between February 2010 and September 2010, sixty women suspected of having breast cancer by clinical examination and mammography underwent bilateral breast MRI and DW imaging (with maximum b values of 600, 800, and 1000 s/mm(2)). Conspicuity grades of lesions at different b values on DW images were performed. Signal intensity and apparent diffusion coefficient (ADC) values were recorded and compared among different b values by the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and receiver operating characteristic (ROC) curve. RESULTS: Fifty-seven lesions from 52 recruited patients including 39/57 (68%) malignant and 18/57 (32%) benign were confirmed with pathology. DCE MRI accurately detected 53 lesions with the sensitivity of 93.0% and specificity of 66.7%, and DW imaging accurately detected 51 lesions with the sensitivity of 89.5% and specificity of 100%. There were no significant differences in conspicuity grades compared among the three b values (P = 0.072), although the SNR and CNR of breast lesions decreased significantly with higher b values. Mean ADCs of malignant lesions (b = 600 s/mm(2), 1.07 ± 0.26 × 10-3 mm(2)/s; b = 800 s/mm(2), 0.96 ± 0.22 × 10-3 mm(2)/s; b = 1000 s/mm(2), 0.92 ± 0.26 × 10-3 mm(2)/s) were significantly lower than those of benign lesions (b = 600 s/mm(2), 1.55 ± 0.40 × 10-3 mm(2)/s; b = 800 s/mm(2), 1.43 ± 0.38 × 10-3 mm(2)/s; b = 1000 s/mm(2), 1.49 ± 0.38 × 10-3 mm(2)/s) with all P values <0.001, but there were no significant differences among the three b values (P = 0.303 and 0.840 for malignant and benign lesions, respectively). According to the area under the ROC curves, which were derived from ADC and differentiate malignant from benign lesions, no significant differences were found among the three b values (P = 0.743). CONCLUSIONS: DW imaging is a potential adjunct to conventional MRI in the differentiation between malignant and benign breast lesions. Varying the maximum b value from 600 to 1000 s/mm(2) does not influence the conspicuity of breast lesions on DW imaging at 1.5 T.

One-pot, three-component synthesis of a library of spirooxindole-pyrimidines catalyzed by magnetic nanoparticle supported dodecyl benzenesulfonic acid in aqueous media.

Dodecyl benzenesulfonic acid functionalized silica-coated magnetic nanoparticles (γ-Fe2O3@SiO2-DDBSA) were readily prepared and identified as an efficient catalyst for the synthesis of a library of spirooxindole-pyrimidine derivatives by three-component condensation reaction of barbituric acids, isatins and cyclohexane-1,3-diones. The aqueous reaction medium, easy recovery of the catalyst using an external magnet, and high yields make the protocol sustainable and economic.

Cerium ammonium nitrate-catalyzed multicomponent reaction for efficient synthesis of functionalized tetrahydropyridines.

A highly atom-economic one-pot synthesis of functionalized tetrahydropyridines by a multicomponent condensation reaction of ß-keto ester, two equivalents of aromatic aldehyde, and two equivalents of amine in the presence of a catalytic amount of cerium ammonium nitrate (CAN) is reported. In this way, a series of pharmacologically interesting substituted piperidine derivatives were obtained in moderate to good yields at room temperature.

Health risk evaluation for the inhabitants of a typical mining town in a mountain area, South China.

A previous study investigated metal contamination in farmland and the air in a typical mining town of Guangxi, South China. In this study, the health risks associated with exposure to this contamination that were evaluated for the following routes of exposure are reported: inhalation, dermal contact, ingestion of dust, and ingestion of homegrown vegetables. The findings demonstrated that the inhabitants were at high risk for noncancer effects posed by some of the metals. The total hazard index (THI) of all the pathways was 145 for adults and 560 for children, which were far higher than the normative level 1. The noncancer risk mainly came from air PM(10) pollution through inhalation and ingestion routes of exposure. However, vegetable ingestion also made a noticeable contribution to HI of about 7 for adults and 22 for children. The metals that posed the greatest noncancer risks were Mn for inhalation, and ingestion of dust and vegetables. The total cancer risks of the inhabitants were 1 x 10(-1) (adult) and 3 x 10(-1) (child), which far exceeded the acceptable carcinogen risk of 10(-4) approximately 10(-6) for regulatory purposes. The cancer risk in the village is mainly (97%) associated with As exposure by inhalation and ingestion of dust. However, consumption of vegetables is also associated with a significant cancer risk of up to 2 x 10(-3) for adults and 8 x 10(-3) for children. The cancers associated with this exposure are estimated to be lung cancer and skin cancer. Air particulate-matter pollution was the main source of noncancer risk and cancer risk and originated from vehicular transport of ore through the community. The risk could be tested by a specifically designed epidemiological study.

[Ultraviolet absorption spectra of iodine, iodide ion and triiodide ion].

Ultraviolet absorption spectra of iodine I2, iodide ion I(-) and triiodide ion I3(-) were studied, and molar absorptivities of these species were determined. Absorption spectrum of I2 aqueous solution appears as an absorption peak at 203 nm with a molar absorptivity of 1.96 x 10(4) L x mol(-1) x cm(-1). Absorption spectrum of I(-) appears as two absorption peaks at 193 and 226 nm with molar absorptivities of 1.42 x 10(4) and 1.34 x 10(4) L x mol(-1) x cm(-1), respectively. When I2 aqueous solution is mixed with KI solution, two absorption peaks appear at 288 and 350 nm, respectively, indicating the formation of I3(-). Using saturation method, molar absorptivities of I3(-) at 288 and 350 nm were determined to be 3.52 x 10(4) and 2.32 x 10(4) L x mol(-1) x cm(-1), respectively.

[Resonance light scattering of aurintricarboxylic acid].

Resonance light scattering (RLS), absorption and fluorescence spectra of aurintricarboxylic acid (ATA) were studied. In solutions with pH 3.7 to pH 11.0, the RLS signal was very weak, but increased sharply with a decrease in pH when pH < 3.7 and reached a maximum at pH 2.7. This enhancement effect of RLS occurred because the negative charged species of ATA were transformed into neutral molecules when pH decreased, and the neutral molecules assembled into supermolecular aggregates. Two peaks at 260 nm and 340 nm, respectively, and a valley at 300 nm, appeared in the RLS spectrum, whereas an absorption peak appeared at 300 nm in the absorption spectrum. This spectral feature reveals that the RLS spectrum was related to the absorption spectrum of ATA. The change in RLS intensity with the wavelength was not accordant with Rayleigh scattering law. The fluorescence excitation and emission spectra of ATA do not overlap, so resonance fluorescence was not involved in the RLS spectrum. Under a given set of experimental conditions, the RLS intensity increased with the increase in ATA concentration, which, however, was not a strictly linear relationship.