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Quality control of animal-derived traditional Chinese medicines has improved dramatically as proteomics research advanced in the past few decades. However, it remains challenging to identify quality attributes with routine proteomics approaches since protein with fibrinolytic activity is rarely reported in pheretima, a typical animal-derived traditional medicine. A novel strategy based on bioinformatics combined with parallel reaction monitoring (PRM) was developed here to rapidly discover the marker peptides associated with a fibrinolytic effect. Potential marker peptides were found by lumbrokinase sequences' alignment and in silico digestion. The fibrinogen zymography was used to visually identify fibrinolytic proteins in pheretima. As a result, it was found that the fibrinolytic activity varied among different portions of pheretima. Fibrinolytic proteins were distributed regionally in the anterior and anterior-mid portion and there was no significant fibrinogenolytic activity observed in the mid-posterior and posterior portion. Finally, PRM experiments were deployed to validate and quantify selected marker peptides and a total of 11 peptides were identified as marker peptides, which could be potentially used in quality control of pheretima. This strategy provides a robust workflow to benefit the quality control of other animal-derived traditional medicines. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The aim of this study was to depict a comprehensive description of near miss research and clarify research gaps. BACKGROUND: Learning from near miss can provide early warnings and is critical for proactive and prospective risk management. Because of the lack of structured reviews, there is little knowledge about how near miss management has been managed in the past. METHODS : This review was conducted following the Arksey and O'Malley's methodology and reported by the PRISMA Extension for Scoping Reviews. RESULTS : Sixty-seven research articles were included. The results revealed that the most investigated fields include near miss reporting, near miss characteristics, and good catch project. Poor theoretical investigation, underreporting, and inconsistent outcome indicators are major problems. CONCLUSIONS: Solely understanding causes of near misses cannot guarantee effective learning; we also need to apply appropriate learning theories. Advanced technologies should be applied to solve long-standing underreporting issues. Accurate and consistent indicators should be applied in near miss research and management. [ABSTRACT FROM AUTHOR]

In this note, we revisit the result of the Toeplitz matrix inversion formula proposed by Lv and Huang (2007), then we give a new structured perturbation analysis, which is useful for testing the stability of practical algorithms. It has been shown that our new upper bound is much sharper than the one they have given, especially when the size of the Toeplitz matrix is very large. Numerical experiments illustrate the effectiveness of our theoretical results. [ABSTRACT FROM AUTHOR]

For solving an augmented linear system, Njeru and Guo presented an accelerated SOR-like (ASOR) method in (P. N. Njeru and X.-P. Guo. Accelerated SOR-like method for augmented linear systems, BIT Numerical Mathematics. 56, 557–571 2016). By further accelerating the ASOR method, we introduce another parameter and propose a modified ASOR method. We first characterize properties about eigenpairs of the iteration matrix, then discuss the convergence of the modified ASOR method. Numerical experiments are given to show the effectiveness of the modified ASOR method. [ABSTRACT FROM AUTHOR]

Achieved herein is a novel diversity‐oriented one‐pot multicomponent synthesis of polycyclic pyrrolidinyl‐dispirooxindoles 3. The key pyrrolidine forming reaction is the 1,3‐dipolar cycloaddition event of isatylidenyl‐chromanones 2 with azomethine ylides (thermally generated in situ from isatins and proline or thioproline). Products bearing four consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure, were smoothly obtained in high yields (up to 89% yield) with good diastereoselectivity (up to >20:1). Valuable feature of this method was the design of new hybrid architectures for biological screenings through creating molecular diversity and complexity by means of the generation of several bonds and rings in a single operation. In particular, their biological activity against human leukemia cells K562 and normal L929 cells have been evaluated. These results suggested changes of this chromanone group could obviously impact the activity, and a chromanone group located in the polycyclic pyrrolidinyl‐dispirooxindoles is beneficial for the activity. What is more, the results also indicated that chromanone‐fused polycyclic pyrrolidinyl‐dispirooxindoles 3 have selective cytotoxicity against cancer cells K562 compared with normal cells L929. [ABSTRACT FROM AUTHOR]

In this study, a rapid and reliable pretreatment method called dispersive liquid-liquid microextraction (DLLME) was developed for the determination of 4(5)-methylimidazole (4-MeI) in beverages. The clean-up samples were analyzed by a high performance liquid chromatography coupled with triple quadrupole mass spectrometer (HPLC–MS/MS) using a reversed-phase C18 column (250 mm × 4.6 mm, 5 μm). The matrix effects and the fault of DLLME operation were corrected by the isotope dilution technique. The developed method exhibited the limit of quantification (0.3 μg L −1 ) and excellent linearity (R 2  = 0.999). In addition, the recovery values of 4-MeI in carbonated beverage were ranging from 102.60% to 113.22%, in soft drinks were ranging from 103.24% to 108.85%. The content 4-MeI was detected in thirteen beverage samples treated with DLLME and solid phase extraction method (SPE) (ranging from 6.4 to 165.5 μg L −1 ). The consistent result of 4-MeI content detected by DLLME and SPE method concluded that the established method on the basis of DLLME was rapid, robust and accurate for the trace 4-MeI determination in beverages. [ABSTRACT FROM AUTHOR]

Exponential discriminant analysis (EDA) is a generalized discriminant analysis method based on matrix exponential. It can essentially overcome the intrinsic difficulty of small-sample-size problem that exists in the classical linear discriminant analysis (LDA). However, for data with high dimensionality, one has to solve a large matrix exponential eigenproblem in this method, and the time complexity is dominated by the computation of exponential of large matrices. In this paper, we propose two inexact Krylov subspace algorithms for solving the large matrix exponential eigenproblem efficiently. The contribution of this work is threefold. First, we consider how to compute matrix exponential-vector products efficiently, which is the key step in the Krylov subspace method. Second, we compare the discriminant analysis criterion of EDA and that of LDA from a theoretical point of view. Third, we establish the relationship between the accuracy of the approximate eigenvectors and the distance to nearest neighbor classifier, and show why the matrix exponential eigenproblem can be solved approximately in practice. Numerical experiments on some real-world databases show the superiority of our new algorithms over their original counterpart for face recognition. [ABSTRACT FROM AUTHOR]

Reported is a facile and efficient methodology toward the synthesis of novel pyrimidine-fused spiropyrrolidine oxindoles via a multicomponent 1,3-dipolar cycloaddition reaction of pyrimidine-fused 3-alkenyloxindoles 1 with azomethine ylides (thermally generated in situ from sarcosine and formaldehyde). Products bearing adjacent quaternary–tertiary centers were smoothly obtained in high yields (up to 90% yield) with good diastereoselectivity (up to >20:1). In addition, their biological activity has been preliminarily demonstrated by in vitro evaluation against human lung cancer cells A549, human prostate cancer cells PC-3, and human leukemia cells K562 by the MTT-based assays, using the commercially available broad-spectrum anticancer drug of Cisplatin as a positive control. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines of K562, PC-3, and A549, showed comparably potent or even more potent than the positive control of Cisplatin (up to 3.0 times), and indicated that novel pyrimidine-fused spiropyrrolidine oxindoles may be potential leads for further biological screenings and may generate drug-like molecules. [ABSTRACT FROM AUTHOR]

Developed herein was an expedient method toward the synthesis of pyrimidine-fused 3-alkenyloxindoles 4 via a Knoevenagel condensation/S N Ar sequential reaction of pyrimidine aldehydes 1 with 2-oxindoles 2 using alcohols 3 as both the solvents and the reactants. A wide variety of products, which is a typical hybridization of two key structural skeletons of 3-alkenyl-oxindole and pyrimidine found in an array of biologically active natural products and pharmaceutical compounds, were obtained smoothly with high efficiency (up to 93% yield) and high ( E/Z )-selectivities (up to >20:1 E/Z ). Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays using the commercially available broad-spectrum anticancer drug Cisplatin as a positive control. These results suggested that most of pyrimidine-fused 3-alkenyloxindoles 4 showed equipotent or more potent than the positive control of Cisplatin (up to 5.1 times), which suggested that pyrimidine-fused 3-alkenyloxindoles 4 may be potential leads for further biological screenings. [ABSTRACT FROM AUTHOR]

The null linear discriminant analysis method is a competitive approach for dimensionality reduction. The implementation of this method, however, is computationally expensive. Recently, a fast implementation of null linear discriminant analysis method was proposed in the paper of Sharma et al. In this method, a random matrix multiplication with scatter matrix is used to produce the orientation matrix. In this paper, we consider whether the random matrix can be replaced by an arbitrary full rank matrix of appropriate size, and focus on the necessary and sufficient condition to guarantee full column rank of the orientation matrix. We investigate how to choose the matrix properly, such that the two criteria of the null linear discriminant analysis method are satisfied. Furthermore, we give a necessary and sufficient condition to guarantee full column rank of the orientation matrix, and describe the geometric characterization of this condition. Numerical experiments justify our theoretical analysis. [ABSTRACT FROM AUTHOR]

We revisit the shift-and-invert Arnoldi method proposed in [S. Lee, H. Pang, and H. Sun. Shift-invert Arnoldi approximation to the Toeplitz matrix exponential, SIAM J. Sci. Comput., 32: 774-792, 2010] for numerical approximation to the product of Toeplitz matrix exponential with a vector. In this approach, one has to solve two large-scale Toeplitz linear systems in advance. However, if the desired accuracy is high, the cost will be prohibitive. Therefore, it is interesting to investigate how to solve the Toeplitz systems inexactly in this method. The contribution of this paper is in three regards. First, we give a new stability analysis on the Gohberg-Semencul formula (GSF) and define the GSF condition number of a Toeplitz matrix. It is shown that when the size of the Toeplitz matrix is large, our result is sharper than the one given in [M. Gutknecht and M. Hochbruck. The stability of inversion formulas for Toeplitz matrices, Linear Algebra Appl., 223/224: 307-324, 1995]. Second, we establish a relation between the error of Toeplitz systems and the residual of Toeplitz matrix exponential. We show that if the GSF condition number of the Toeplitz matrix is medium-sized, then the Toeplitz systems can be solved in a low accuracy. Third, based on this relationship, we present a practical stopping criterion for relaxing the accuracy of the Toeplitz systems and propose an inexact shift-and-invert Arnoldi algorithm for the Toeplitz matrix exponential problem. Numerical experiments illustrate the numerical behavior of the new algorithm and show the effectiveness of our theoretical results. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a case study of 40‐year‐old Chinese woman with medical history presented with a right breast lump. Topics discussed include ultrasonography of the right breast, ultrasound‐guided core biopsy of the nodule revealed a low‐grade fibromyxoid stromal proliferation and nodular mucinosis of the breast.

Inspired by the chemistry and biology of isoflavones and pyrazolones, herein we report the first example of synthesis of 3-pyrazolyl isoflavones by two steps, starting from commercially available chromanones and pyrazolones. The [1,5]-proton transfer was used as a key strategy. All the 3-pyrazolyl isoflavones 3 , which are hard to synthesize by traditional methods, are smoothly obtained in up to 86% total yield. Interestingly, the product forms a stable 7-membered ring through intramolecular hydrogen bond between carbonyl group on chromone core and hydroxyl group on pyrazolone core, preventing further ketone-enol tautomerization. In particular, the products are featured with an intriguing combination of two privileged motifs including isoflavone and pyrazolone substructures, which might be valuable in medicinal chemistry. Image 1 • The first example of synthesis of 3-pyrazolyl isoflavones. • [1,5]-hydrogen transfer as the key step. • Potential biologically active molecules. [ABSTRACT FROM AUTHOR]

A series of novel derivatives of 18β-glycyrrhetinic acid (GA) were synthesized by introducing aromatic or heterocyclic structures to extend the side chain, thereby enhancing their interaction with amino acid residues in the active pocket of the target protein. These compounds were structurally characterized using 1H NMR, 13C NMR, and HRMS. The compounds were subsequently evaluated for their inhibitory effects on HIV-1 protease and cell viability in the human cancer cell lines K562 and HeLa and the mouse cancer cell line CT26. Towards HIV-1 protease, compounds 28 and 32, which featured the introduction of heterocyclic moieties at the C3 position of GA, exhibited the highest inhibition, with inhibition rates of 76% and 70.5%, respectively, at 1 mg/mL concentration. Further molecular docking suggests that a 3-substituted polar moiety would be likely to enhance the inhibitory activity against HIV-1 protease. As for the anti-proliferative activities of the GA derivatives, incorporation of a thiazole heterocycle at the C3- position in compound 29 significantly enhanced the effect against K562 cells with an IC50 value of 8.86 ± 0.93 µM. The introduction of electron-withdrawing substituents on the C3-substituted phenyl ring augmented the anti-proliferative activity against Hela and CT26 cells. Compound 13 exhibited the highest inhibitory activity against Hela cells with an IC50 value of 9.89 ± 0.86 µM, whereas compound 7 exerted the strongest inhibition against CT26 cells with an IC50 value of 4.54 ± 0.37 µM. These findings suggest that further modification of GA is a promising path for developing potent novel anti-HIV and anticancer therapeutics. [ABSTRACT FROM AUTHOR]

For the given signature operator H = I r ⊕ − I n − r , a pseudo-Jacobi matrix is a self-adjoint matrix relatively to a symmetric bilinear form 〈 ⋅ , ⋅ 〉 H , and it is the counterpart of a classical Jacobi matrix to the indefinite scalar product space setting. In this article, we consider an inverse eigenvalue problem for this class of matrices. The main concern is to construct an n × n pseudo-Jacobi matrix from a prescribed n -tuple of distinct real numbers and a Jacobi matrix of order not less than ⌊ n 2 ⌋ , such that its spectrum is this tuple and the given Jacobi matrix is its trailing principal submatrix. A divide-and-conquer scheme is used to solve this problem, and a necessary and sufficient condition under which the problem is solvable is presented. A numerical algorithm is designed to solve this pseudo-Jacobi matrix inverse eigenvalue problem according to the obtained results. Some illustrative numerical examples are also given to test the reconstructive algorithm. [ABSTRACT FROM AUTHOR]

C16H12O3, monoclinic, P21/c (no. 14), a = 10.9636(14) Å, b = 12.1767(12) Å, c = 10.1557(13) Å, β = 116.588(16)°, V = 1212.4(3) Å3, Z = 4, Rgt(F) = 0.0366, wRref(F2) = 0.1019, T = 250.00(10) K. [ABSTRACT FROM AUTHOR]

Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract of G. elegans exhibited significant antitumor activity with IC50 values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1–2) were then screened for cytotoxicity. Interestingly, compound 2 showed moderate cytotoxicity against K562 leukemia cells with an IC50 value of 57.02 uM. [ABSTRACT FROM AUTHOR]

Diamide insecticides, represented by chlorantraniliprole (CHL), were widely applied in the control of lepidopteran insects. In efforts to develop bioactive diamides with novel scaffolds, we design and synthesized a series of diamides containing central amino acids to conformationally simulate CHL. Bioassay results indicated that most compounds containing 1‐aminocyclopropane‐1‐carboxylic acid exhibited excellent larvacidal potency against Mythimna separate and Plutella xylostella. After a systematic structure–activity relationship study, 1–23 was identified as a potential insecticidal candidate with LC50 values of 34.920 mg·L−1 against M. separate and 61.992 mg·L−1 on P. xylostella. Finally, molecular docking revealed the possible binding mode of 1–23 with the target protein, ryanodine receptors. [ABSTRACT FROM AUTHOR]

The slurry ability of lignite is too poor to be applied directly to coal-water slurry gasification technology. Luhuo lignite sample was pretreated differently by acid/water washing and pyrolysis in order to improve its slurryability. The treated samples were characterized by BET test, proximate analysis, ultimate analysis experiments, etc. The results show that the pore structure of the coal samples is destroyed by pretreatment, specific surface area decreases and average pore size increases, and the slurry concentration and mobility are improved. The concentration of coal water slurry can rise to 60% in the study of the slurryability of pretreated lignite washed with acid. The TherMax500 thermogravimetric apparatus was introduced to study the gasification characteristics of differently pretreated lignite. The results reveal that pretreatment with water washed has little effect on coal gasification reactivity, but acid washing pretreatment greatly reduces gasification reactivity of luhuo lignite. [ABSTRACT FROM AUTHOR]

Background: Detection of vulnerable plaques could be clinically significant in the prevention of cardiovascular events. We aimed to compare Fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in vulnerable and stable plaques, and investigate the feasibility of predicting thrombosis events using Positron Emission Tomography/Computed Tomography (PET/CT) angiography. Methods: Atherosclerosis was induced in 23 male New Zealand white rabbits. The rabbits underwent pharmacological triggering to induce thrombosis. A pre-triggered PET/CTA scan and a post-triggered PET/CTA scan were respectively performed. 18F-FDG uptake by the aorta was expressed as maximal standardized uptake value (SUVmax) and mean SUV (SUVmean). SUVs were measured on serial 7.5 mm arterial segments. Results: Thrombosis was identified in 15 of 23 rabbits. The pre-triggered SUVmean and SUVmax were 0.768±0.111 and 0.804±0.120, respectively, in the arterial segments with stable plaque, and 1.097±0.189 and 1.229±0.290, respectively, in the arterial segments with vulnerable plaque (P<0.001, respectively). The post-triggered SUVmean and SUVmax were 0.849±0.167 and 0.906±0.191, respectively in the arterial segments without thrombosis, and 1.152±0.258 and 1.294±0.313, respectively in the arterial segments with thrombosis (P<0.001, respectively). The values of SUVmean in the pre-triggered arterial segments were used to plot a receiver operating characteristic curve (ROC) for predicting thrombosis events. Area under the curve (AUC) was 0.898. Maximal sensitivity and specificity (75.4% and 88.5%, respectively) were obtained when SUVmean was 0.882. Conclusions: Vulnerable and stable plaques can be distinguished by quantitative analysis of 18F-FDG uptake in the arterial segments in this rabbit model. PET/CT may be used for predicting thrombosis events and risk-stratification in patients with atherosclerotic disease. [ABSTRACT FROM AUTHOR]

• Citropten markedly alleviated DSS-induced acute and recurrent colitis. • Citropten dramatically decreased the production of pro-inflammatory mediators in colon tissues and effectively suppressed the proportion of Th17 cells in spleen. • Citropten significantly inhibited the activation of NF-κB and JAK/STAT3 signaling pathways. Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease, which is characterized by inflammation, with many symptoms including diarrhea, abdominal pain, bloody stool, and weight loss. It is difficult to completely cure and promising therapeutic drug candidates are urgently needed. Citropten, a coumarin-like compound found in traditional Chinese medicine such as Finger Citron Fruit, notopterygium root and citrus peel, has been shown to inhibit the proliferation of tumor cells, protect against depression and suppress the production of inflammatory mediators. In this study, we demonstrated that citropten could alleviate dextran sulfate sodium (DSS)-induced acute and recurrent colitis in mice, with significant improvement in body weight loss, disease activity index, shortened colon length and histological changes. Moreover, citropten dramatically decreased the production of pro-inflammatory mediators in colon tissues and effectively suppressed the proportion of Th17 cells in spleen. Mechanism investigations revealed that citropten significantly inhibited the activation of NF-κB and JAK/STAT3 signaling pathways, thus leading to decreased inflammation, Th17 cells and alleviative colitis. These findings provide novel insights into the anti-colitis effect of citropten, which may be a promising drug candidate for treatment of IBD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel compound 1 possessed a benzophenone skeleton with a farnesyl side chain. • The methanol and dichloromethane extractions of H. lancasteri exhibited significant antiradical effects. • The IC 50 value of compound 4 was closest to that of the positive control drug ascorbic acid. • This work provided systematic biological targeted study on antiradical activity from active extracts to novel compound. A novel benzophenone lancasteriphenone A (1), one new natural product 2,4-dihydroxy-6-(3-methylbut-2-enoxy) phenyl]-phenylmethanone (2), along with two known compounds (3 and 4) were isolated and identified from the aerial parts of Hypericum lancasteri. Their structures were elucidated by means of spectroscopic techniques. Novel compound 1 possessed a benzophenone skeleton with a farnesyl side chain. DPPH radical scavenging activities were tested to determine the antioxidant potential of the methanol extract, dichloromethane extract as well as the isolated compounds (1 – 4). Its methanol and dichloromethane extracts exhibited significant antiradical effect with IC 50 values of 20.84 µg/mL and 60.63 µg/mL, respectively. Besides, the antiradical activitise of the compounds 1 – 4 from active dichloromethane extract were also tested. The DPPH radical scavenging rates of the compounds 1 – 4 were 33.07%, 24.59%, 17.67% and 86.56% at the concentration of 400 µmol/L, respectively, while the IC 50 value (97.53 µmol/L) of compound 4 was closest to that of the positive control drug ascorbic acid (IC 50 = 58.13 µmol/L). This work provided systematic biological targeted study on antioxidant activity from active extracts to novel compound, and shed a new light on the further antioxidant application research of H. lancasteri. [ABSTRACT FROM AUTHOR]

Abstract In the present work, we investigated the influence of deformation temperature on the formation of a bimodal microstructure and tensile properties of a Mg–9Al–1Zn (AZ91) alloy processed by a single pass hard plate rolling (HPR) with a thickness reduction of 55% followed by a short time annealing. Microstructural examinations by electron backscatter diffraction (EBSD) reveal that there exists a narrow deformation temperature window, i.e. it is only feasible to achieve a desired bimodal grain structure in the AZ91 alloy when HPRed at ∼350 °C. It is mainly because that partial dynamic recrystallization (DRX) occurs easily in the sample HPRed at ∼ 350 °C, facilitating the formation of a bimodal microstructure consisting of coarse un–recrystallized grains (>∼70 μm) and fine recrystallized grains (<∼5 μm). In contrast, reducing deformation temperature to ∼300 °C results in a coarse unrecrystallized microstructure containing substantial sub structure, while elevating the deformation temperature to ∼400 °C leads to an almost uniform recrystallized grain structure. Especially, the formation mechanism for the bimodal grain structure at the optimum deformation temperature is explored in terms of Schmidt factors analysis for basal slips (SF basal ) for grains of different size scales. Moreover, the 350 °C HPRed AZ91 sample exhibits a better combination of strength (ultimate tensile strength = ∼374 MPa) and ductility (elongation = ∼19.6%), as compared to the 300 and 400 °C samples. It is mainly attributed to the typical bimodal grain structure and the relatively high SF basal featured by the fine recrystallized grains as well as the nanometer spherical particles distributing in fine grain interiors. Graphical abstract Image 1 Highlights • A bimodal grain structure of Mg–9Al–1Zn alloy was achieved by tailoring rolling temperature during hard–plate rolling (HPR). • The formation of bimodal microstructure was explored in terms of Schmidt factors analysis for basal slips (SF basal ). • The formation of bimodal grain structure generated a simultaneous improvement of strength and ductility. [ABSTRACT FROM AUTHOR]

A new methodology was developed for the synthesis of 3,3′-pyrrolidinyl-dispirooxindoles 3 through a 1,3-dipolar cycloaddition event of isatylidenyl-chromanones 2 with azomethine ylides (thermally generated in situ from isatins and sarcosine). The method gives an easy access to a series of highly functionalized products containing three consecutive stereocenters and vicinal spiroquaternary stereocenters fused in one ring structure with 15 examples in high yields (up to 82% yield) and good diastereoselectivity (up to >20:1), which makes possible the synthesis of libraries under similar circumstances. Moreover, the current method provides a convenient approach for the efficient incorporation of two biologically important scaffolds (chromanone and 3,3′-pyrrolidinyl-dispirooxindoles). X-ray diffraction studies of one of the cycloadducts proved the structure and regiochemistry of the cycloaddition. In particular, their biological activity against human leukemia cells K562 and normal L929 cells has been evaluated. These results suggested that 3,3′-pyrrolidinyl-dispirooxindoles 3 may be potential leads for further biological screenings. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of bone mesenchymal stem cells (BMSCs) and BMSC neural-like cells (BMSC-Ns) on the spinal cord injury (SCI) in the rat model of SCI. BMSC-Ns were prepared from the third passage of BMSCs by induction of healthy cerebrospinal fluid (CSF) of an adult human. The SCI rat model was established through a surgical procedure, and after 7 days the rats were randomly divided into 3 (A, B and C) groups. Groups A (BMSC-Ns) and B (BMSCs) were treated with 1 × 10 6 /20 μl cells, while group C (saline) was treated with saline, all via intracerebroventricular injection. After transplantation, the BBB score of group A was significantly higher than that of group B, which in turn was significantly higher than that of group C ( P <  .05). The levels of Bdnf, Ngf, Ntf3 were statistically significantly higher in group A than those in groups B and C ( P <  .05). The levels of 5-HT, NA, Ach, DA, GABA in group A were significantly higher than those in groups B and C, whereas the level of Glu was significantly lower in group A than that in groups B and C ( P <  .05). The histopathological data showed remarkably less necrosis of the spinal cord in group A, compared to that in groups B and C. Transplanting BMSC-Ns or BMSCs into the lateral ventricles improved the neurological function of rats with SCI. Moreover, BMSC-Ns were significantly more effective than BMSCs, which provides a possible approach for the treatment of SCI. [ABSTRACT FROM AUTHOR]

Described herein is a facile and efficient methodology toward the synthesis of novel convolutamydine A‐incorporated β‐ionone scaffold 3 from an Aldol addition event of β‐ionone to isatins via enamine Et2NH catalysis. Products featuring a quaternary carbon center were smoothly obtained in good yields (up to 96% yield). This protocol also represents the first construction of ionone skeleton‐fused oxindole molecules, thus leading to new knowledge in the fields of both molecular complexity and diversity‐oriented synthesis and the lead compound discovery. Furthermore, their biological activities against human leukemia cells K562 have been preliminarily demonstrated by in vitro assays. The results demonstrated that most of these compounds obtained by this protocol showed comparable with or even much better than the positive control of Cisplatin. [ABSTRACT FROM AUTHOR]

We have developed an efficient and straightforward methodology for the synthesis of novel tanshinone-substituted bis(indolyl/pyrrolyl)methane scaffolds 3 through TsOH catalysis-enabled addition of indoles or pyrroles 1 with tanshinones 2 based on molecular hybridization strategy. Products were smoothly obtained in good yields (up to 81% yield). This protocol also represents the first construction of tanshinone skeleton-fused bis(indolyl/pyrrolyl)methane scaffolds, thus leading to new knowledge in the fields of both molecular complexity and diversity-oriented synthesis and the lead compound discovery. Furthermore, their biological activities against human leukemia cells K562, human prostate cancer cells PC-3, and human lung cancer cells A549 have been preliminarily demonstrated by in vitro assays. The results demonstrated that most of these compounds 3 obtained by this protocol showed comparable activity to the positive control of cisplatin. [ABSTRACT FROM AUTHOR]

miR-758-3p plays an important role via regulting ABCA1-mediated cholesterol efflux in atherosclerosis. However, the mechanism of miR-758-5p in cholesterol metabolism is still unclear. Here, we revealed that miR-758-5p decreased total cholesterol accumulation in THP-1 macrophage derived foam cells through markedly reducing cholesterol uptake, and no effect on the cholesterol efflux. Interestingly, computational analysis suggests that CD36 may be a target gene of miR-758-5p. Our study further demonstrated that miR-758-5p decreased CD36 expression at both protein and mRNA levels via targeting the CD36 3′UTR in THP-1 macrophage derived foam cells. The present present study concluded that miR-758-5p decreases lipid accumulation of foam cell via regulating CD36-mediated the cholesterol uptake. Therefore, targeting miR-758-5p may offer a promising strategy to treat atherosclerotic vascular disease. [ABSTRACT FROM AUTHOR]

Developed herein is a diversity-oriented one-pot multicomponent synthesis of polycyclic 3,3′- pyrrolidinyl-dispirooxindoles 3 via a multicomponent 1,3-dipolar cycloaddition event of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles 2 with azomethine ylides (thermally generated in situ from isatins and proline or thioproline). Products bearing four consecutive stereocenters consist of two oxindole moieties and a polycyclic pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure were smoothly obtained in high yields (up to 85% yield) with good diastereoselectivity (up to >20:1). Valuable features of this method were application of 3-methyl-4-nitro-5-isatylidenyl-isoxazoles as 1,3-dipolarophiles and the design of new hybrid architectures for biological screenings through the adequate fusion of these sub-units of isoxazole and 3,3′-pyrrolidinyl-dispirooxindole, generating drug-like molecules. [ABSTRACT FROM AUTHOR]

Described herein is a facile and efficient methodology toward the synthesis of Morusin scaffolds and Morusignin L scaffolds 4 – 9 and 12 via a novel three-step approach (Michael addition or prenylation, cyclization and cyclization) and use a rapid, microwave-accelerated cyclization as the key step. Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation for anti-osteoporosis activity. These Morusin, Morusignin L and newly synthesized compounds 5b , 6a , 8e , 8f greatly exhibited the highest potency, especially at the 10 −5 mol/L (P < 0.01), and had good in vitro anti-osteoporosis activities using the commercially available standard drug Ipriflavone as a positive control. The mechanisms associated with anti-osteoporosis effects of these compounds may be through the inhibition of TRAP enzyme activity and bone resorption in osteoclasts, and promotion effect of osteoblast proliferation in vitro . The results indicated that Morusin scaffolds and Morusignin L scaffolds may be useful leads for further anti-osteoporosis activity screenings. [ABSTRACT FROM AUTHOR]

Described herein is a facile and efficient methodology for diversity-oriented one-pot multicomponent synthesis of 3-aminomethyl quaternary carbon oxindole fused five-membered carbocyclic spirooxindoles 5 via knoevenagel condensation/Michael/cyclization and then aminomethylation reaction. A wide variety of products with varying degrees of substitution around it, were obtained smoothly with high efficiency (up to overall yield 73% and >20:1 diastereoselectivity). In particular, their biological activities against these three cell lines K562, A549 and PC-3 have been evaluated. These results suggested that most of 3-aminomethyl quaternary carbon oxindole fused five-membered carbocyclic spirooxindoles 5 showed equipotent or more potent than the positive control of Cisplatin (up to 3.4 times). [ABSTRACT FROM AUTHOR]

Objective: In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs). Methods: PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted. Results: Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61–0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57–0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33–0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents. Conclusion: Our results indirectly suggest that BP-stainless DESs may offer more benefits than BP-alloy DESs in the era of BP-DESs. Further well-designed RCTs comparing BP-stainless with BP-alloy DESs are needed to confirm which platform is better. [ABSTRACT FROM AUTHOR]

Developed herein is a facile and efficient methodology toward the synthesis of novel turmerone motif-fused spiropyrrolidine oxindoles via a multicomponent 1,3-dipolar cycloaddition event of dienones 2 with azomethine ylides (thermally generated in situ from isatin derivatives and sarcosine). Products bearing adjacent quaternary–tertiary centers were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). In addition, their biological activity has been preliminarily demonstrated by in vitro evaluation against human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays, using the commercially available standard drug of Cisplatin as a positive control. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these two cell lines of K562 and A549, showed comparably potent or even more potent than the positive control of Cisplatin (up to 5.1 times), and indicated that novel turmerone motif-fused spiropyrrolidine oxindoles may be potential leads for further biological screenings and may generate drug-like molecules. [ABSTRACT FROM AUTHOR]

A facile and efficient methodology was developed for the synthesis of multifunctional polycyclic spiropyrrolidine oxindoles bearing mesityl oxide unit via a three-component 1,3-dipolar cycloaddition reaction of dienones 2 with azomethine ylides (thermally generated in situ from isatin derivatives and proline or thioproline). Products bearing adjacent four chiral carbon centers were smoothly obtained in high yields (up to 98% yield) with diastereoselectivities up to >20:1. Furthermore, the key structural characteristic of the products of such a reaction is the natural product ingredient turmerone motif fused at the 3-position of the spirooxindole core, with varying degrees of substitution around it. In addition, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays, using the commercially available standard drugs Cisplatin as a positive control. These results suggested there is a trend that lipophilicity groups improve the potency, and also suggested an mesityl oxide moiety located in the polycyclic spiropyrrolidine oxindoles is beneficial for the activity. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines K562, A549 and PC-3, and indicated that polycyclic spiropyrrolidine oxindole analogs bearing mesityl oxide unit may be potential leads for further antitumor activity screenings. [ABSTRACT FROM AUTHOR]

A novel chiral phosphoric acid catalyst bearing two acidic phenolic hydroxyl groups was synthesized. Its as a chiral Brøsted acid has been examined in the Friedel-Crafts and enones as a model reaction. In comparison with the other chiral phosphoric acid catalysts, the reaction catalyzed by the novel chiral catalyst afforded the desired 3-substituted indoles in a higher (up to 69% ee). [ABSTRACT FROM AUTHOR]

A direct competitive enzyme-linked immunosorbent assay (ELISA) with monoclonal antibody (MAb) was diagnosed with progesterone (P) level of human serum. In high concentrations and large amounts of displacer effect, this monoclonal antibody (MAb) can retain biological activity so that it can be specially combined with progesterone. Under conditions of the existing displaced agent, monoclonal antibody 11F8(3)H5 can maintain high specificity and affinity and can specifically bind progesterone in serum. Progesterone ELISA standard curve was calculated according to the following formula: Logit(y)=−1.358Log(x)+0.4961, r=0.9944. The serum progesterone values obtained by this method correlated well with those obtained by chemiluminescent immunoassay (CLIA): the correlative equation was y=0.7804x+0.7600, r=0.9126. [ABSTRACT FROM AUTHOR]

The well-known toxic medicine Gelsemium elegans is widely and historically used to treat bone fracture and skin ulcers by the folk people of China. Two new monoterpenoid indole alkaloids, gelselegandines D and E, together with the known analogue gelegamine A were isolated from G. elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. All isolated compounds were tested for the effects on RANKL-induced osteoclast formation. Interestingly, gelselegandine E and gelegamine A, respectively, showed significant promoting and inhibitory activities on osteoclastogenesis, while gelselegandine D had no activity under the same concentration. This work suggested the different configurations for the carbons near the C-19/20 oxygen rings of the isolated compounds may be the key active groups on osteoclast formation and provided the evidence for the rationality as the traditional treatment for bone-related diseases of G. elegans. [ABSTRACT FROM AUTHOR]

An organic, ultrathin, and transparent sound-emitting device was fabricated using poly(3,4-ethylenedioxythiophene):poly(styrenesulfonic) (PEDOT:PSS) films. This sound-emitting device was easily processed by spin coating. Sound emission from PEDOT:PSS was measured as a function of power, distance, and frequency. The sound frequency spectrum was found to be ultra-flat in a wide sound frequency range (10-45 kHz). Theoretical analysis showed that the working principle was the thermoacoustic effect. The PEDOT:PSS sound-emitting device has potential applications in the acoustic field. In particular, it can be integrated with a liquid crystal display to realize sound emission and image display at the same time. [ABSTRACT FROM AUTHOR]

A series of structurally diverse chrysin-chromene-spirooxindole hybrids were designed, synthesized via a Knoevenagel/Michael/cyclization of chrysin and isatylidene malononitrile derivatives through utilizing a hybrid pharmacophore approach. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds showed stronger anti-proliferative activity than parent compound chrysin. In particular, compound 3e had the highest cytotoxicity towards A549 cells (IC 50 = 3.15 ± 0.51 μM), and had better selectivity in A549 cells and normal MRC-5 cells. Furthermore, compound 3e could significantly inhibit the proliferation and migration of A549 cells in a dose-dependent manner, as well as induce the apoptosis possibly through mitochondria-mediated caspase-3/8/9 activation and multi-target co-regulation of the p53 signaling pathway. Thus, our results provide in vitro evidence that compound 3e may be a potential candidate for the development of new anti-tumour drugs. Unlabelled Image • The first example of flavonoid-fused spirooxindoles. • A molecular hybridization strategy. • Compound 3e induced cancer cell apoptosis as a potential anticancer agent. [ABSTRACT FROM AUTHOR]

Facile and efficient methodology for the synthesis of novel turmerone motif-fused spiropyrrolidine oxindoles via a multicomponent 1,3-dipolar cycloaddition reaction of dienones with azomethine ylides is reported. [ABSTRACT FROM AUTHOR]

A facile and efficient methodology is developed for the synthesis of multifunctional polycyclic spiropyrrolidine oxindoles via a three-component 1,3-dipolar cycloaddition reaction of dienones (III) with azomethine ylides (thermally generated in situ from isatin derivatives and proline or thioproline). [ABSTRACT FROM AUTHOR]