Gold-Catalyzed Intramolecular Hydroarylation and Transfer Hydrogenation of N-Aryl Propargylamines to Construct Tetrahydroquinolines and 5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolines.

A novel protocol of gold-catalyzed N-aryl propargylamines to construct tetrahydroquinolines and 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolines in moderate to good yields has been developed through the tandem reactions of intramolecular hydroarylation and transfer hydrogenation. The strategy has the advantages of easy access to raw materials, simple reaction conditions, good substrate compatibility, high efficiency, and excellent regioselectivity.

Towards Axially Chiral Pyrazole-Based Phosphorus Scaffolds by Dipeptide-Phosphonium Salt Catalysis.

Given the comparatively lower rotational barriers, the catalytic asymmetric construction of axially chiral biaryl structures, especially those containing a five-membered heterocycle, still remains a challenge. Herein, we described a general and modular protocol to access atropisomeric arylpyrazole scaffolds containing a phosphorus unit by a dipeptide phosphonium salt catalyzed reaction involving an oxidative central-to-axial chirality conversion. This reaction features excellent yields and enantioselectivities, broad substrate scope, and a low catalyst loading, delivering axially chiral phosphine compounds.

Cardiopulmonary exercise test-based assessment of the effects of sacubitril/valsartan on the blood pressure response to exercise in patients with acute myocardial infarction during hospitalization.

OBJECTIVE: To investigate the effects of sacubitril/valsartan (S/V) on cardiopulmonary function and blood pressure response to exercise during hospitalization in patients with acute myocardial infarction (AMI) based on the cardiopulmonary exercise test (CPET). METHODS: A total of 265 AMI patients were treated with either perindopril or S/V within 24 hours of admission. CPET was completed for all patients before discharge. There were 182 cases in the perindopril group and 83 cases in the S/V group. RESULTS: The proportion of exercise oscillatory ventilation (EOV) was higher in the S/V group than in the perindopril group (10.8% vs 1.6%, X2 = 11.148, P = .001). The resting heart rate (HR), resting diastolic blood pressure (DBP), and warm-up DBP were lower in the S/V group than in the perindopril group (P < .05). The resting systolic blood pressure (SBP) was 9.0 mmHg lower (115.7 ± 17.5 vs 106.7 ± 15.0, P < .001), the SBP during warm-up was 9.5 mmHg lower (124.8 ± 23.7 vs 115.3 ± 22.5,P = .002), the SBP at the anaerobic threshold (AT) was 10.5 mmHg lower (135.3 ± 24.8 vs 127.1 ± 25.1,P = .021),the SBP at max watts was 11.5 mmHg lower (148.9 ± 26.4 vs 137.4 ± 26.4,P = .001), and the SBP during one-minute recovery was 12.3 mmHg lower (146.5 ± 27.1 vs 134.2 ± 24.4, P = .001)in the S/V group than in the perindopril group. The S/V group had a higher oxygen ventilation equivalent and carbon dioxide ventilation equivalent (VE/VCO2) at AT and a lower oxygen uptake-work rate relationship during max watts (P < .05). The differences in the oxygen pulse, stroke volume, peak oxygen uptake (VO2 peak), and VE/VCO2 slope were not statistically significant between the two groups. CONCLUSION: Treatment with S/V was able to reduce the exercise blood pressure in patients with AMI during hospitalization, but did not significantly improve the VO2 peak, VE/VCO2 slope, or exercise tolerance.

Enantiodivergent Kinetic Resolution of 1,1'-Biaryl-2,2'-Diols and Amino Alcohols by Dipeptide-Phosphonium Salt Catalysis Inspired by the Atherton-Todd Reaction.

A highly enantiodivergent organocatalytic method is disclosed for the synthesis of atropisomeric biaryls via kinetic resolution inspired by a dipeptide-phosphonium salt-catalyzed Atherton-Todd (A-T) reaction. This flexible approach led to both R- and S-enantiomers by fine-tuning of bifunctional phosphonium with excellent selectivity factors (s) of up to 1057 and 525, respectively. The potential of newly synthesized O-phosphorylated biaryl diols was illustrated by the synthesis of axially chiral organophosphorus compounds. Mechanistic investigations suggest that the bifunctional phosphonium halide catalyst differentiates between the in-situ-generated P-species in the A-T process, mainly involving phosphoryl chloride and phosphoric anhydride, thus leading to highly enantiodivergent O-phosphorylation reactions. Furthermore hydrogen bonding interactions between the catalysts and phosphorus molecules were crucial in asymmetric induction.

Multiple crystallization as a potential strategy for efficient recovery of succinic acid following fermentation with immobilized cells.

This study aimed to enhance the crystallizability of bio-based succinic acid for its efficient recovery while maintaining the end product at the highest purity. Immobilization of Actinobacillus succinogenes was initially evaluated based on three different carriers: volcanic glass, clay pebbles, and silica particles. The adsorption capacity of metabolites with a low concentration (10 g/L) and a high concentration (40 g/L) was investigated. It was demonstrated that clay pebbles adsorbed the least succinic acid (< 11 mg/g clay pebbles). The repeated batch-fermentation trials with immobilized cells highlighted that succinic acid with an average concentration of up to 36.3 g/L with a metabolite-production ratio of 3:1 (succinic acid to by-products) could be attained within 130 h. Subsequently, the purification of succinic acid through crystallization was assessed in terms of pH, temperature, crystallization time, initial succinic acid concentration and multiple recrystallization processes. Increasing the crystallization time from 6 h to 9 h afforded an improvement of 17% in the recovery of succinic acid crystals. Moreover, a fourfold concentration coefficient of the broth yielded the highest purity percentage (99.9%). The crystallization in three consecutive stages at 9 h (with a fourfold concentration coefficient) successfully improved the total recovery percentage of succinic acid from 55.0 to 84.8%.

Homogeneous solid dispersion (HSD) system for rapid and stable production of succinic acid from lignocellulosic hydrolysate.

Continuous bio-production of succinic acid was reported in homogeneous solid dispersion (HSD) system utilizing porous coconut shell activated carbon (CSAC) as immobilization carrier. The aim of the present work was to implement the HSD system to increase the area of cell immobilization and the rate of succinic-acid production from the lignocellulosic medium. The ratio of the two enzymes (cellulase-to-hemicellulase) was initially optimized to break down the lignocellulose into its free monomers, wherein the best ratio was determined as 4:1. Succinic-acid production was evaluated in the HSD system by varying the substrate loading and dilution rate. The results showed that high productivities of succinic acid were obtained when 60 g/L glucose was fed over a dilution rates ranging from 0.03 to 0.4/h. The titer of succinic acid decreased gradually with higher dilution rate, whereas the residual substrate concentration increased with it. Critical dilution rate was determined to be 0.4/h at which the best productivity of succinic acid of 6.58 g/L h and its yield of 0.66 g/g were achieved using oil palm fronds (OPF) hydrolysate. This work lends evidence to the use of CSAC and lignocellulosic hydrolysate to further exploit the potential economies of scale.

Highly Enantioselective Synthesis of Fused Tri- and Tetrasubstituted Aziridines: aza-Darzens Reaction of Cyclic Imines with α-Halogenated Ketones Catalyzed by Bifunctional Phosphonium Salt.

The first enantioselective aza-Darzens reaction of cyclic imines with α-halogenated ketones was realized under mild reaction conditions by using amino-acid-derived bifunctional phosphonium salts as phase-transfer promoters. A variety of structurally dense tri- and tetrasubstituted aziridine derivatives, containing benzofused heterocycles as well as spiro-structures, were readily synthesized in high yields with excellent diastereo- and enantioselectivities (up to >20:1 d.r. and >99.9 % ee). The highly functionalized aziridine products could be easily transformed into different classes of biologically active compounds.

[2,6-Bis(5-eth-oxy-1,3-oxazol-2-yl)-4-meth-oxy-phenyl-κ(3) N,C (1),N']bromidopalladium(II).

In the title compound, [PdBr(C17H17N2O5)], the Pd(II) atom is coordinated by an N,C(1),N'-tridentate pincer ligand and a Br atom in a distorted square-planar geometry. In the crystal, mol-ecules are connected by C-H⋯Br and C-H⋯O hydrogen bonds, and π-π inter-actions between the oxazole and benzene rings [centroid-centroid distance = 3.7344 (19) Å], resulting in a three-dimensional supra-molecular structure.

[Coagulation and prothrombotic state parameters: clinical analysis in early pregnancy].

OBJECTIVE: To assess the changes in coagulation, thrombosis, anti-coagulation and fibrinolysis during early pregnancy. METHODS: A total of 105 gravidas with monocytic pregnancies between 10 and 12 weeks gestational age at Sun Yat-sen Memorial Hospital, Sun Yat-sen University during April 2005 to June 2009 were recruited for study group and another 82 non-pregnant women as control group. Coagulation parameters, including thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin (PT) and fibrinogen (Fg), were measured. We also tested the prothrombotic state parameters, including prothrombin fragment 1+2 (F1+2), thrombomodulin (TM), thrombin-antithrombin complex (TAT), antithrombin III(AT-III), GMP140, thromboxane B2 (TXB2), plasminogen activator inhibitor (PAI-2; performed by enzyme-linked immunosorbent assay) and D-dimer (D2; tested by latex turbidimetric immunoassay). RESULTS: Fg (4.00 vs 2.52 g/L), F1+2 (0.66 vs 0.31 nmol/L), TAT (179.95 vs 39.46 µg/L), GMP140 (9.42 vs 19.13 µg/L), D2 (201.51 vs 125.02 µg/L) and PAI-2 (0.047 vs 0.006 g/L) were statistically different between the study and control groups (P < 0.01). CONCLUSIONS: The coagulation, fibrinolysis and anti-fibrinolysis functions of healthy pregnant women become enhanced during early pregnancy while anti-coagulation function slightly increases. These four basic functions are balanced at a higher level so that the activation of platelets stays at a lower level.

[Modulation of low molecular weight heparin and heparin-binding epidermal growth factor on biological functions of human first trimester trophoblast].

OBJECTIVE: To evaluate the effects of low molecular weight heparin (LMWH) and heparin-binding epidermal growth factor (HB-EGF) on the biological function of human trophoblast in first trimester. METHODS: From Feb. 2011 to Nov. 2011, the trophoblast isolated from human first trimester chorionic villi was cultured in vitro. Based on variation of LMWH concentration, the trophoblast was classified into 0.025 U/ml group, 0.25 U/ml group, 2.5 U/ml group, 25 U/ml group and 250 U/ml group. In the mean time, based on treatment of heparin, the trophoblast was classified into LMWH group (0.25 U/ml), HB-EGF group (10 µg/L), combination group (LMWH at 0.25 U/ml + HB-EGF at 10 µg/L) and add with DMEM as control group. Cell proliferation was assessed by the methyl thiazolyl tetrazolium (MTT) test, which was showed with the mean absorbance as A value. Cell invasion was measured by transwell, which counted the number of cells migrated to the superficies inferia of filter membrane. Cell differentiation was assessed by the concentration of hCG secretion. RESULTS: Compared with control group, the trophoblast proliferation and invasion treated by LMWH at 0.025 U/ml did not show significant difference (P > 0.05). When treated by LWMH at 0.25 U/ml and 2.5 U/ml, trophoblast proliferation and invasion was increased significantly (P < 0.05). When LMWH at 25 U/ml and 250 U/ml, it could inhibit trophoblast proliferation and invasion (P < 0.05). When compared with A value of 0.44 ± 0.04 in control group, the increased A value were 0.51 ± 0.05 in LMWH group, 0.56 ± 0.04 in HB-EGF group and 0.69 ± 0.06 in combination group (P < 0.05). In the transwell test, the cell number were 511 ± 78 in LMWH group, 669 ± 67 in HB-EGF group and 872 ± 64 in combination group, which were significantly higher than 405 ± 67 in control group (P < 0.05), respectively. And the hCG concentration were (7143 ± 649) U/L in LMWH group, (11 762 ± 1059) U/L in HB-EGF group and (11 015 ± 1084) U/L in combination group, which showed statistical difference with (8182 ± 666) U/L in control group (P < 0.05). CONCLUSION: LMWH could modulate trophoblast proliferation, invasion, and differentiation. HB-EGF is one of important factors involved in effects of LMWH on trophoblast function.

Biotechnological enhancement of lactic acid conversion from pretreated palm kernel cake hydrolysate by Actinobacillus succinogenes 130Z.

The aim of this study was to establish an improved pretreatment and fermentation method i.e. immobilized cells for high recovery of fermentable sugars from palm kernel cake (PKC) and its effects on fermentability performance by Actinobacillus succinogenes 130Z in the conversion of the fermentable sugar to lactic acid. The effects of oxalic acid concentrations (1-6% w/v) and residence times (1-5 h) on the sugar recovery were initially investigated and it was found that the highest mannose concentration was 25.1 g/L at the optimum hydrolysis conditions of 4 h and 3% (w/v) oxalic acid. The subsequent enzymatic saccharification of the pretreated PKC afforded the highest enzymatic digestibility with the recovered sugars amounting to 25.18 g/L and 9.14 g/L of mannose and glucose, respectively. Subsequently, the fermentability performance of PKC hydrolysate was evaluated and compared in terms of cultivation phases (i.e. mono and dual-phases), carbonate loadings (i.e. magnesium and sodium carbonates), and types of sugars (i.e. glucose and mannose). The highest titer of 19.4 g/L lactic acid was obtained from the fermentation involving A. succinogenes 130Z in dual-phase cultivation supplemented with 30 g/L of magnesium carbonate. Lactic acid production was further enhanced by using immobilized cells with coconut shell-activated carbon (CSAC) of different sizes (A, B, C, and D) in the repeated batch cultivation of dual-phase fermentation producing 31.64 g/L of lactic acid. This work sheds light on the possibilities to enhance the utilization of PKC for lactic acid production via immobilized A. succinogenes 130Z.

Suzuki-Miyaura coupling of aryl iodides, bromides, and chlorides catalyzed by bis(thiazole) pincer palladium complexes.

Bis(thiazole) pincer palladium complexes showed efficient catalytic activity for the Suzuki-Miyaura coupling of aryl halides, allowing the synthesis of biaryls with very high turnover numbers and turnover frequencies. The complexes were successfully applied in the scalable and green synthesis of the key intermediates of bioactive LUF5771 and its analogues.

Asymmetric synthesis of N-bridged [3.3.1] ring systems by phosphonium salt/Lewis acid relay catalysis.

Optically pure pseudo-natural products (PNPs), particularly exemplified by azabicyclo[3.3.1]nonane molecules and their analogs provide an attractive platform for structure-activity relationship studies, and also lead new compound discovery in drug development. However, there are currently no examples of guiding catalytic asymmetric strategies available to construct such important PN-scaffolds, thus limiting their broad use. Here, we report a general and modular method for constructing these pseudo-natural N-bridged [3.3.1] ring systems via cascade process by bifunctional phosphonium salt/Lewis acid relay catalysis. A wide variety of substrates bearing an assortment of functional groups (59 examples) are compatible with this protocol. Other features include a [3 + 2] cyclization/ring-opening/Friedel-Crafts cascade pathway, excellent reactivities and stereoselectivities, easily available starting materials, step economy and scalability. The obtained enantioenriched products showed potential of preliminary anticancer activities. Insights gained from our studies are expected to advance general efforts towards the catalytic synthesis of challenging even unprecedented chiral PNPs, offering new opportunities for bioactive small-molecule discovery.

Research on Intelligent Identification of Pivoting Center and Smooth Processing of Test Data for Flying Flexible Joint.

In this paper, a method of intelligent identification and data smooth processing of flying flexible joint pivoting center based on machine vision is proposed. The intelligent identification is realized by the following process: first of all the geometric center of the two markers attached to the flying body is located on a straight line at a certain angle to the center-line of the measured pivoting body, secondly then continuous image sampling is carried out by industrial camera when the marker swings with the pivoting body, and image data is transmitted through a data interface to an industrial computer, Finally the image processing module de-noises the image, removes the background and locates the markers to obtain the plane coordinates of the markers in the coordinate system of the test system. The data smooth of obtained coordinates is carried outby Matlab software including the following steps: the coordinates of the mark points detected based on machine vision are optimized to obtain the smooth curve by fitting of the parabola and arc. Then the coordinates of the points on the curve are used to optimize the coordinates of the marked points from measurement. The optimized coordinate values are substituted into the calculation module of pivoting center, so the average pivoting center of the sampling interval of two images is calculated according to the mathematical model to approach the instantaneous pivoting center during the motion of the pivoting body. The result processing module displays and records the curve of pivoting center shift directly and effectively. Finally, it is validated by simulation and experiments that the precision of pivoting center measured by such measuring system is ~0.5%.

Research on monitoring method for thinning spinning process of the ultra-thin-walled cylinder based on the drum shape.

In order to perceive the state of the process of reverse thinning spinning of the ultra-thin wall tube, a monitoring method based on drum shape is proposed. The method uses the non-uniform rational basis spline curve fitting method based on the moving least squares method to reconstruct the outer contour data of the spinning zone collected by the line laser displacement sensor and extracts the outer contour curve of the drum zone according to the spinning characteristics. Then, the dynamic time warping algorithm is used to analyze the similarity between the current and previous drum curves in order to judge whether the current spinning state is abrupt or not. At the same time, the current spinning state is judged by combining the curvature comb of the drum curve, the number of convex areas of the drum curve, the drum ratio, and the drum change trend. Finally, the drum shape detection and the spinning condition monitoring experiments are carried out. The experimental results show that this method can obtain the outer contour shape of the drum section at one time, and the accuracy is 0.05 mm with respect to the measured value of the three coordinates. The method can realize the visual monitoring of the abrupt change of the spinning process by judging the similarity of the drum curve at the adjacent time under different spinning states. In the state of instability, the curvature comb of the drum curve is discontinuous, the curve is G0 continuous, the drum ratio exceeds the critical drum ratio 2.0, and there is more than one convex region, which realizes the monitoring of spinning state more accurately. The experimental results verify the correctness of the proposed method and prove that the method can be used as a new method to judge the stability of the ultra-thin-walled cylinder spinning process.

[Efficacy of photodynamic therapy for peri-implantitis: A meta-analysis].

PURPOSE: This meta-analysis was undertaken to evaluate the efficacy of photodynamic therapy (PDT) in combination with non-surgical therapy compared to non-surgical therapy alone for patients with peri-implantitis. METHODS: Bibliographic databases including Cochrane Library, PubMed, EMbase, Web of Science, CNKI, VIP, Wanfang Data and CBM were searched from inception to April 1st 2018 , to collect randomized controlled trials (RCTs) of photodynamic therapy in combination with non-surgical therapy and non-surgical therapy alone for peri-implantitis. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the quality. Then after cross-checking, meta analyses was performed by using RevMan 5.3 software. Meta analysis of probing depth (PD), bleeding on probing(BOP) and clinical attachment level(CAL) was conducted using weighted mean differences (WMD) for continuous data with 95% confidence intervals(CI). RESULTS: Six studies met the inclusion criteria. Meta analysis results showed that compared to non-surgical therapy alone, PDT in combination with non-surgical therapy showed significant differences in PD(WMD=-0.81,95%CI -1.52 to -0.11, P=0.02), BOP(WMD=-5.15, 95%CI -6.29 to -4.01, P<0.00001), but no significant differences in CAL(WMD=-1.13, 95%CI -3.51 to 1.25, P=0.35). CONCLUSIONS: In the treatment of peri-implantitis, compared to non-surgical therapy alone, non-surgical therapy with PDT was more effective in reduction of probing depth and probing bleeding, but it did not significantly improve clinical attachment level. For the quantity and quality limitation of the included studies, the conclusion has to be further proved by performing more well-designed and high quality RCTs.

Catalyst-Free Synthesis of α-Functionalized 2H-Chromenes in Water: A Tandem Self-Promoted pseudo-Substitution and Decarboxylation Process.

A catalyst-free decarboxylative reaction between ß-keto acids and 2H-chromene acetals in water was developed. This reaction featured a broad substrate scope and easily obtainable starting materials to afford α-functionalized 2H-chromenes in high yields. The synthetic value of this protocol was also demonstrated by the scale-up synthesis and versatile conversions of the title product into other useful compounds. In addition, control experiments indicated that water was essential for the reactivity. Mechanistic studies further revealed that the reaction proceeded through a self-promoted tandem pseudo-substitution and decarboxylation process.

Bifunctional Phosphonium Salt Directed Enantioselective Formal [4 + 1] Annulation of Hydroxyl-Substituted para-Quinone Methides with α-Halogenated Ketones.

A highly diastereo- and enantioselective [4 + 1] cycloaddition of para-quinone methides to α-halogenated ketones was realized by bifunctional phosphonium salt catalysis, furnishing functionalized 2,3-dihydrobenzofurans in high yields and excellent stereoselectivities (>20:1 dr and up to >99.9% ee). Mechanistic observations suggested that the reaction underwent a cascade intermolecular substitution/intramolecular 1,6-addition process. DFT calculations revealed the presence of multiple H-bonding interactions between the catalyst and the enolate intermediate in the stereodetermining transition states.

[Clinical experience of using oxytocin antagonist atosiban in the rescue therapy of preterm labour].

OBJECTIVE: To investigate the effectiveness of oxytocin antagonist atosiban in the alternative rescue therapy of preterm labor. METHODS: Alternative tocolysis atosiban was given as rescue therapy to 35 women, who had received ritodrine or magnesium sulphate but failed, due to either progression of labour or intolerable adverse events. Atosiban was administered for up to 48 hours. Efficacy and tolerability were assessed based on the proportion of women who did not deliver and did not need alternative tocolytic therapy at 48 hours and 7 days after therapy initiation. The numbers of maternal adverse events and neonatal morbidity were also assessed. RESULTS: Efficacy and tolerability at 48 hours and 7 days after atosiban initiation were 77% (27/35) and 60% (21/35). One woman presented drug-related side effects with mild nausea and vomiting. Thirty-four women have delivered and one bigemina (28 weeks) is being followed-up. In 34 women, 11 delivered before 28 gestational weeks, 17 delivered after 28 gestational weeks, 3 delivered after 34 weeks and 3 had term delivery. Pregnancies were prolonged by 4 hours to 14(+2) weeks. There were nine neonatal deaths, with gestational ages less than 28 weeks at delivery. CONCLUSION: Oxytocin antagonist atosiban could be given as alternative rescue therapy if therapy with ritodrine or magnesium sulphate fails in the treatment of preterm labor, and it is safe and effective.

Preeminent productivity of 1,3-propanediol by Clostridium butyricum JKT37 and the role of using calcium carbonate as pH neutraliser in glycerol fermentation.

Calcium carbonate was evaluated as a replacement for the base during the fermentation of glycerol by a highly productive strain of 1,3-propanediol (PDO), viz., Clostridium butyricum JKT37. Due to its high specific growth rate (µmax=0.53h-1), 40g/L of glycerol was completely converted into 19.6g/L of PDO in merely 7h of batch fermentation, leaving only acetate and butyrate as the by-products. The accumulation of these volatile fatty acids was circumvented with the addition of calcium carbonate as the pH neutraliser before the fermentation was inoculated. An optimal amount of 15g/L of calcium carbonate was statistically determined from screening with various glycerol concentrations (20-120g/L). By substituting potassium hydroxide with calcium carbonate as the pH neutraliser for fermentation in a bioreactor, a similar yield (YPDO/glycerol=0.6mol/mol) with a constant pH was achieved at the end of the fermentation.