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Background: Atherosclerosis is one of the leading causes of morbidity and mortality worldwide. A variety of long noncoding RNAs (lncRNAs) have been reported to be significantly involved in vascular smooth muscle cell (VSMC) proliferation, which is an essential process for atherosclerotic plaque formation. The aim of this study was to investigate the mechanism of lncRNA urothelial cancer associated 1 (UCA1) involvement in atherosclerosis. Method: The effects of oxidized low-density lipoprotein (oxLDL) and UCA1 on VSMC proliferation and colony-forming ability was measured by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, real-time polymerase chain reaction (PCR), and western blots, as well as to determine the effect that oxLDL has on UCA1 expression, and the effect of oxLDL and UCA1 on the expression of cyclin-dependent kinase 2 (CDK2). Results: oxLDL treatment increased the proliferation rate of VSMCs in a concentration-dependent manner. Importantly, UCA1 apparently increased the viability of VSMCs as the VSMCs exhibited a significantly reduced growth rate when UCA1 expression was knocked down by specific small interfering RNAs (siRNAs). In conjunction with increasing cell viability, oxLDL also enhanced the colony-forming ability of VSMCs while UCA1 siRNA decreased the colony-forming ability of VSMCs. Furthermore, UCA1 significantly decreased the percentage of VSMCs in G1 phase, while increasing their percentage in S phase. In contract siRNA knockdown of UCA1 caused an increased percentage of cell in G1 phase, and a reduction in the percentage of cells in S phase. Using real-time PCR and western blot assays, we showed that oxLDL significantly increased the expression levels of UCA1 and CDK2. Furthermore, UCA1 siRNA and CDK2 siRNA almost abolished the positive effect of oxLDL on CDK2 expression. Finally, overexpression of UCA1 induced an increase in CDK2 levels, and knockdown of UCA1 caused inhibition of CDK2 expression. Conclusion: Upregulation of UCA1 enhances abnormal proliferation of VSMC by promoting G1/S transition through modulating the expression of CDK2.

In the present study, a series of unreported fluorinated dabigatran analogues, which were based on the structural scaffold of dabigatran, were designed by computer-aided simulation. Fifteen fluorinated dabigatran analogues were screened and synthesized. All target compounds were characterized by (1)H NMR, (13)C NMR, (19)F NMR and HRMS. According to the preliminary screening results of inhibition ratio, eleven analogues (inhibition ratio >90%) were evaluated for antithrombin activity in vitro (IC50). The test results expressed that all the analogues showed effective inhibitory activities against thrombin. Especially, compounds 8f, 8k and 8o, with IC50 values of 1.81, 3.21 and 2.16nM, respectively, showed remarkable anticoagulant activities which were in the range of reference drug dabigatran (IC50=1.23nM). Moreover, compounds 8k and 8o were developed to investigate their anticoagulant activities in vivo. In those part, compound 8o exhibited a fairly strong inhibitory action for arteriovenous thrombosis with inhibition ratio of 84.66%, which was comparable with that of dabigatran (85.07%). Docking simulations demonstrated that these compounds could act as candidates for further development of novel anticoagulant drugs.

In this work, 48 thrombin inhibitors based on the structural scaffold of dabigatran were analyzed using a combination of molecular modeling techniques. We generated three-dimensional quantitative structure-activity relationship (3D-QSAR) models based on three alignments for both comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) to highlight the structural requirements for thrombin protein inhibition. In addition to the 3D-QSAR study, Topomer CoMFA model also was established with a higher leave-one-out cross-validation q(2) and a non-cross-validation r(2), which suggest that the three models have good predictive ability. The results indicated that the steric, hydrophobic and electrostatic fields play key roles in QSAR model. Furthermore, we employed molecular docking and re-docking simulation explored the binding relationship of the ligand and the receptor protein in detail. Molecular docking simulations identified several key interactions that were also indicated through 3D-QSAR analysis. On the basis of the obtained results, two compounds were designed and predicted by three models, the biological evaluation in vitro (IC50) demonstrated that these molecular models were effective for the development of novel potent thrombin inhibitors.

A series of fluorinated dabigatran analogs were designed and synthesized. All the target compounds were characterized by 1H NMR, 13C NMR, and FT-ICR-MS. The thrombin inhibitory activities of the new synthesized compounds were also evaluated in vitro. The results show that compound 12a has the highest IC50 of thrombin inhibition (IC50 = 5.41 nM). Moreover, molecular docking simulation was carried out to elucidate the conformations of the compounds and key amino acid residues at the active site of thrombin protein. The results show there is an appropriate relationship between IC50 and the docking scores for compounds 12a–e. We suggest that the hydrogen bond interaction between Asp189, Gly219 of thrombin and the compounds appear to play major role in thrombin inhibition.

Capsella bursa-pastoris L. (C. bursa-pastoris) was treated by hot air drying, microwave drying, vacuum drying and freeze-drying, respectively, to analyze the influences on aroma components using gas chromatography-mass spectrometry. The results showed that the freeze-dried product enjoyed significantly alleviated color changes, short rehydration time, high rehydration ratio and retention rates of chlorophyll and vitamin C. Vacuum drying functioned inferior to freeze-drying but superior to hot air drying and microwave drying. As for aroma components, both vacuum drying and freeze-drying managed to preserve the characteristic aroma components in C. bursa-pastoris. In summary, vacuum drying and freeze-drying retained the color, texture, morphology as well as grass and leaf aromas of C. bursa-pastoris in maximum, but the former method, which lasts a shorter time and consumes less energy, should be given first priority in large-scale industrial practice. Practical Applications C. bursa-pastoris suffers from a plummet of nutritional value and loss of economic benefits even within short harvest and storage periods. Drying newly harvested C. bursa-pastoris with appropriate techniques can both meet different consumer demands and effectively prolong the shelf life of products. Various drying techniques are bound to affect sensory attributes and retention rates of nutrients and aroma components significantly. We treated fresh C. bursa-pastoris by vacuum drying, hot air drying, microwave drying and freeze-drying, and compared the quality of final products, aiming to find out the optimum drying method and parameters and while providing valuable practical evidence for industrial drying of this vegetable.

The human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is generally regarded as a target for the treatment of acquired immune deficiency syndrome (AIDS). Non-nucleoside RT inhibitors (commonly known as NNRTIs) are currently being used in the treatment of HIV-1 infections. In this work, a series of NNRTIs were studied using a combination of molecular modeling techniques including three-dimensional quantitative structure–activity relationship (3D-QSAR), Topomer CoMFA and molecular docking simulations. The best optimum comparative molecule field analysis (CoMFA) model yielded a leave-one-out correlation coefficient (q2) and a non-cross-validated correlation coefficient (r2) of 0.636 and 0.993, respectively. The respective q2 and r2 of the best comparative molecular similarity indices analysis (CoMSIA) model were 0.655 and 0.998. The models were validated by test sets, and predicted correlation coefficients (rpred2) of 0.907 and 0.886 obtained from the CoMFA and CoMSIA models, thus judging the robustness of the model. The analysis of Topomer CoMFA obtained a q2 of 0.546 and a rpred2 value of 0.718 which suggested the model had a good predictive ability (q2 > 0.2). The results indicated the steric, hydrophobic and electrostatic fields play key roles in the models. Molecular docking elucidated the conformations of the compounds and key amino acid residues at the docking pocket of RT protein.

A series of dabigatran derivatives were designed and synthesized to discover effective thrombin inhibitors. All the target compounds were characterized by 1H NMR, 13C NMR and HRMS. These compounds were evaluated in vitro and showed potent anticoagulant activities against thrombin. Among these compounds, the ethyl group substitution at N-1 of benzimidazole exhibited better anticoagulant activity against thrombin. Especially, compound 10i showed an IC50 of 2.04 nM. Docking simulations demonstrated that compound 10i could bind tightly with the crystal structure of the thrombin active site. Based on the results obtained, compound 10i may act as a candidate compound for further development of direct thrombin inhibitors.

We provide the raw data for protein and peptide identification and quantization of superior and inferior spikelets in hybrid rice during grain filling. The mass spectrometry proteomics data have been deposited to the Proteome Xchange Consortium via the PRIDE partner repository with the dataset identifier PXD001046. Our data presented here is also related to the article “Comparative proteomics analysis of superior and inferior spikelets in hybrid rice during grain filling and response of inferior spikelets to drought stress using isobaric tags for relative and absolute quantification ”in the Journal of Proteomics [1].

A new series of resveratrol heterocyclic analogs (4a–m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure–activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC50 = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC50 = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4′-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F1-ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.

High temperature after anthesis may degrade the grain quality of rice (Oryza sativa L.). To understand the effect of stress duration (initial and mid grain filling stages) and the influence to grain quality at different spikelet positions, an indica cultivar and a japonica cultivar, Yangdao 6 and Yangjing 9538, were used in a pot experiment under 35 °C during the initial (8–18 d after anthesis) and mid (18–28 d after anthesis) terms of grain filling. The treatment under normal atmospheric temperature (25–27 °C) served as the control. The high-temperature treatment at initial filling stage had larger influence on grain quality than the stress imposed at mid filling stage, and the grain quality varied with cultivars and spikelet positions. Both treatments with high temperature reduced milled rice rate and head milled rice rate, but increased crude protein content; grains on the primary branches received larger effect than those on the secondary branches. In the same branch, later-flowered grains were affected greater than early-flowered grains. When high temperature was imposed at initial grain filling stage, the chalkiness degree and chalky grain percentage were significantly increased in the early-flowered grains, whereas the amylose content was significantly decreased; such variations were larger in grains on the primary branches than those on the secondary branches. Besides, the 2 cultivars showed different responses of grain quality to high-temperature stress, which indicated the fact of phenotypic difference on temperature sensitivity. Generally, the influence of temperature on rice quality was greater when the stress imposed at the earlier stage of grain filling.

Three analogs derived from the N-terminal 29-residue fragment of human growth hormone-releasing factor (hGRF) which contained a bicyclic beta-turn dipeptide (BTD) at 7-8, 8-9, and 9-10 positions were synthesized by solid phase methodology to ascertain if the beta-turns are important for the biological activity of hGRF and also to show the applicability of the BTD unit to solid phase synthesis. All three analogs were obtained in good yield and purity indicating that the BTD unit can be used in the usual condition of solid phase synthesis. The capacity of these analogs to release growth hormone (GH) was tested in an in vitro bioassay using rat anterior pituitary cells. All three BTD-containing analogs showed the same maximal GH secretion with parallel dose-response curves to that of hGRF(1-29)NH2, except their relative potencies were very low.

Cooking and nutrition qualities of grain are two of the most important aspects of rice quality. To understand the difference in cooking and nutrition qualities among the grains at different positions within a rice panicle, the distributions of gel consistency (GC), amylose content (AC) and crude protein content (CPC) of grains in a panicle in association with different nitrogen levels (0, 120 and 240 kg/ha) were investigated by using two rice varieties, Yangdao 6 (indica) and Wuyujing 3 (japonica). In general, the grains at the basal part of a panicle had lower GC and higher AC than those at the upper or middle part of a panicle. The 1 st grain on the secondary branch with earlier flowering exhibited the highest GC, whereas the 2 nd grain on the primary branch with later flowering showed the highest AC. For Yangdao 6, CPC in the grains on the primary branches was lower at the middle part of a panicle than at the upper or basal part of a panicle. For Wuyujing 3, there were no significant differences in CPCs in the grains among the upper, middle and basal parts of a panicle. GC in the grains was increased, whereas AC was reduced from zero nitrogen application (0N) to low amount of nitrogen application (LN), and the result was reversed from LN to medium amount of nitrogen application (MN). CPC was increased with the increase in the amount of nitrogen application.

Twenty-one fluorinated dabigatran derivatives were designed based on the bioisosteric principle. All derivatives were synthesised and evaluated for their thrombin inhibitory activity in vitro. Among these compounds, 14h, 14m, 14s and 14t were potent and the activity was in the range of reference drug, dabigatran. Three structural changes were introduced in these 21 compounds to elucidate the structure-activity relationship of the drugs. In addition, prodrugs of compounds 14h and 14s were developed to investigate their anticoagulant activities in vivo. In these experiments, compound 16 showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and demonstrated potent activity for inhibiting arteriovenous thrombosis with an inhibition rate of (73 ± 6) %, which was comparable to that of dabigatran etexilate (76 ± 2) %. Moreover, molecular docking studies were performed to understand the binding interactions of active compounds 14h, 14s and 14t with thrombin protein (PDB ID:1KTS). Contour maps obtained from the 3D-QSAR model are meaningful in designing more active molecules to act as direct inhibitors of thrombin.

Analogs of human and rat growth hormone-releasing factor (hGRF and rGRF), related to [D-Arg 2 ]hGRF(1–29)NH 2 , were synthesized by solid phase methodology. Their capacity to inhibit growth hormone secretion stimulated by hGRF(1–44)NH 2 was tested on rat anterior pituitary cells in monolayer culture. Among the analogs of hGRF, [D-Arg 2,29 ,Arg 30 ]hGRF(1–30)NH 2 showed the highest antagonistic potency of 3.64 relative to [D-Arg 2 ]hGRF(1–29)NH 2 = 1. However, the most potent analog synthesized thus far was [N-Ac-His 1 , D-Arg 2 ,Ala 15 ]rGRF(1–29)NH 2 , which showed a relative potency of 27.7.

Fifty-four analogs of human growth hormone-releasing factor (hGRF) substituted with a single D-amino acid were synthesized by solid phase methodology. Their capacity to release growth hormone was tested on rat anterior pituitary cells in monolayer culture. Among the series of 28 analogs, which had the amino acid at each position of hGRF (1-29)NH2, except glycine at position 15, substituted by the corresponding D-isomer, [D-Ala2]-, [D-Asp3]-, [D-Asn8]-, [D-Tyr10]-, [D-Asp25]-, [D-Met27]-, [D-Ser28]-, and [D-Arg29]hGRF(1-29)NH2 were as potent as hGRF(1-29)NH2, while [D-Ile5]-, [D-Phe6]-, [D-Thr7]-, and [D-Val13]hGRF(1-29)NH2 showed quite low potencies. Effects of substitution with other D-amino acids in positions 2,3,8,9,10 and 11 were also studied. In most cases, the resulting analogs showed decreased potency, but still retained high intrinsic activity. Only [D-Arg2]hGRF(1-29)NH2 showed very low intrinsic activity and some antagonistic property.