bluuebunny/crossref_metadata_2025 huggingface dataset:
Static magnetic field effects on proteases with fibrinolytic activity produced byMucor subtilissimus
Authors: Albuquerque Wendell , Nascimento Thiago , Brandão‐Costa Romero , Fernandes Thiago , Porto Ana
Published: November 2016

The influence of a static magnetic field (SMF) on crude enzyme extracts with proteolytic activity is described and discussed. Proteolytic enzymes, which hydrolyze peptide bonds, and fibrinolytic enzymes, which dissolve fibrin clots, have industrial relevance, and applicability dependent on improvements of productivity and activity. We investigated whether a moderate SMF affects proteolysis in different in vitro tests: general proteolysis of azocasein substrate, and static and dynamic fibrinolytic processes (to compare fibrin gel configuration under exposure). Crude enzyme extracts, obtained from solid state fermentation ofMucor subtilissimusUCP (Universidade Católica de Pernambuco, Recife, Brazil) 1262, were used to carry out assays under slightly heterogeneous fields: a varied vertical SMF (for tests in Eppendorf tubes, from 0.100 to 0.170 T) and a varied horizontal SMF (for tests in Petri dishes, from 0.01 to 0.122 T), generated by two permanent magnets (NdFeB alloy). Results showed significant differences (P < 0.05) in static fibrinolysis assays after 24 h of exposure. The mean diameter of halos of fibrin degradation in the treated group increased by 21% compared to the control group; and the pixel number count of fibrin consumption (in a computational analysis of the area of each halo) enhanced by 30% with exposure. However, in dynamic fibrinolysis assays, no effects of SMF were observed. These results suggest a response of fibrin monomers to the SMF as a possible cause of the observed effects. Bioelectromagnetics. 38:109–120, 2017. © 2016 Wiley Periodicals, Inc.
Exploring the electrochemiluminescent behavior of procaterol hydrochloride in the presence of Ru(bpy)32+ and its analytical application in pharmaceutical preparation
Authors: Kong Dexian , Hu Fangdong , Jiang Lili , Lin Jiandi , Wei Qiaohua , Chi Yuwu , Chen Guonan
Published: November 2016

Based on the strong enhancement effect of procaterol hydrochloride on the electrochemiluminescence (ECL) of Ru(bpy)32+ (bpy = 2,2′‐bipyridine) in an alkaline H3PO4–NaOH buffer solution on a bare Pt electrode, a simple, rapid and sensitive method was developed for the determination of procaterol hydrochloride. The optimum conditions for the enhanced ECL have been developed in detail in this work. Under optimum conditions, the logarithmic ECL enhancement vs. the logarithmic concentration of procaterol hydrochloride is linear over a wide concentration range of 2.0 × 10−7 to 2.0 × 10−4 M (r = 0.9976), with a limit of detection of 1.1 × 10−8 M (S/N = 3), and a relative standard deviation of 2.1% (n = 7, c = 5.0 × 10−6 M). The proposed method was applied to the determination of this drug in tablets with recoveries of 89.7%–98.5%. In addition, a possible mechanism for the enhanced ECL of Ru(bpy)32+, which is caused by ProH, has also been proposed.
Intracellular cysteine oxidation is modulated by aquaporin‐8‐mediated hydrogen peroxide channeling in leukaemia cells
Authors: Vieceli Dalla Sega Francesco , Prata Cecilia , Zambonin Laura , Angeloni Cristina , Rizzo Benedetta , Hrelia Silvana , Fiorentini Diana
Published: November 2016

The modulation of H2O2 production by NADPH oxidase (Nox), on vascular endothelial growth factor (VEGF) stimulation, affects the redox signaling linked to cancer cell proliferation. H2O2 signal transduction involves reversible oxidation of thiol proteins, leading to the formation of cysteine sulfenic acids, responsible for the temporary inactivation of many phosphatases. These events imply that H2O2 reaches its intracellular targets. As Aquaporin‐8 (AQP8) has been demonstrated to funnel Nox‐produced H2O2 across the plasma membrane, this study aims to elucidate the role of AQP8 in the redox signaling occurring in human leukaemia B1647 cells that constitutively produce VEGF. AQP8 overexpression or silencing resulted in the modulation of VEGF ability of increasing or decreasing, respectively, H2O2 intracellular level. Moreover, data obtained by a dimedone‐based immunochemical method for sulfenic acid detection demonstrate that the expression of AQP8 can modulate the amplitude of downstream events, altering the activity of redox‐sensitive targets. In particular, AQP8 affected VEGF‐induced redox signaling by increasing the sulfenation of the tumor suppressor PTEN, which resulted in its inactivation and, in turn, caused Akt activation. Therefore, the dimedone‐based method for easily monitoring cellular protein sulfenation allowed to demonstrate, for the first time, the role of AQP8 on the fine tune of cysteine oxidation in target proteins involved in leukaemia cell proliferation pathways. © 2016 BioFactors, 43(2):232–242, 2017
Novel technique for high throughput measurement of active monooxygenase concentration
Authors: Welters Tim , Horn Thomas , Ruff Anna Joelle , Schwaneberg Ulrich , Büchs Jochen
Published: November 2016

Absorbance measurements via transmitting light spectroscopy in microtiter plates are established for high throughput screening of biological systems. These measurements allow for the determination of important process parameters within a short time. However, absorbance determination via transmitted light measurements is not always feasible. As for carbon monoxide difference absorbance spectroscopy, used for concentration measurements of active P450 monooxygenases (P450s), security standards, and consistent gassing have to be addressed. In this study, a non‐invasive online measuring principle for absorbance via scattered light is proposed. Based on optical fiber measurements, a decrease in scattered light signals at 450 nm wavelength of reflecting polymer particles is observed, and P450 concentrations are calculated. In this way, high throughput determination of P450 concentrations in a secure, gas‐tight environment is realized. The designed method was successfully applied to concentration measurements and carbon monoxide (CO) saturation kinetics ranging from 0.3 to 5.0 μM P450 BM3 achieving a measurement accuracy of ±0.05 μM P450. Biotechnol. Bioeng. 2017;114: 929–933. © 2016 Wiley Periodicals, Inc.
Identification of mineral‐binding peptides that discriminate between chalcopyrite and enargite
Authors: Curtis Susan , Lederer Franziska L. , Dunbar W. Scott , MacGillivray Ross T.A.
Published: November 2016

Innovative approaches to the separation of minerals and subsequent extraction of metals are imperative owing to the increasing mineralogical complexity of ore deposits that are difficult or even impossible to separate into slurries or solutions containing only the minerals or metals of interest. Low recovery of metal is typical for these complex deposits leading to significant losses to tailings. In addition, the minerals often contain impurities, some toxic, which are difficult and costly to control or manage during the processing of a concentrate or other mineral product. One example of this complex situation is the significant economic and environmental costs associated with diluting and processing copper concentrates containing arsenic (in the form of the mineral enargite, Cu3AsS4) in the production of pure copper. To overcome these separation problems, we have utilized phage display to identify peptides that demonstrate selective recognition of enargite and the arsenic‐free copper sulfide, chalcopyrite. Screening of two random peptide phage display libraries resulted in the identification of an enargite‐selective peptide with the sequence MHKPTVHIKGPT and a chalcopyrite‐selective peptide with the sequence RKKKCKGNCCYTPQ. Mineral‐binding selectivity was demonstrated by binding studies, zeta potential determination and immunochemistry. Peptides that have the ability to discriminate between enargite and chalcopyrite provide a greener option for the separation of arsenic containing contaminants from copper concentrates. This represents the first step towards a major advance in the replacement or reduction of toxic collectors as well as reducing the level of arsenic‐bearing minerals in the early stages of mineral processing. Biotechnol. Bioeng. 2017;114: 998–1005. © 2016 Wiley Periodicals, Inc.
Patterns of recurrence after oesophagectomy and postoperative chemoradiotherapy versus surgery alone for oesophageal squamous cell carcinoma
Authors: Hsu P-K , Chen H-S , Huang C-S , Liu C-C , Hsieh C-C , Hsu H-S , Wu Y-C , Wu S-C
Published: November 2016

Background

Patterns of recurrence after surgery with postoperative chemoradiotherapy (S-CCRT) or surgery alone in patients with oesophageal squamous cell carcinoma (SCC) may differ. This might influence the nature and timing of subsequent management strategies.

Methods

Patients with SCC who had undergone R0 resection were included. Propensity score matching was used to select matched groups. Survival and recurrence were compared by Kaplan–Meier analysis. Univariable and multivariable Cox regression analyses were used to identify prognostic factors for overall and disease-free survival.

Results

A total of 1390 patients were included, of whom 1000 had surgery alone and 390 underwent S-CCRT. Propensity score matching yielded 213 well balanced pairs. The 3-year overall survival rate and median survival time in the S-CCRT group were 0·50 and 36·5 (95 per cent c.i. 25·1 to 52·6) months respectively, compared with 0·38 and 22·8 (18·2 to 29·0) months in the surgery-alone group (P = 0·006). The 3-year disease-free survival rate and median disease-free survival time in the S-CCRT group were 0·46 and 30·6 (22·2 to 39·3) months respectively, compared with 0·36 and 17·6 (11·3 to 23·9) months in the surgery-alone group (P = 0·006). The 2-year freedom from locoregional recurrence rate was 0·87 and 0·77 in the S-CCRT and surgery-alone groups respectively (P = 0·003). In multivariable analysis, independent prognostic factors for disease-free survival included age over 56 years, pT3–4 category, pN category, poor differentiation, tumour length exceeding 4·0 cm, and receiving postoperative chemoradiotherapy (hazard ratio 0·62, 95 per cent c.i. 0·47 to 0·81; P < 0·001).

Conclusion

Oesophagectomy with postoperative chemoradiotherapy was associated with longer survival and lower recurrence rates, especially at a locoregional level, compared with surgery alone.
Rapid analysis of interaction between six drugs and β2‐adrenergic receptor by injection amount‐dependent method
Authors: Zeng Kaizhu , Wang Jing , Sun Zhenyu , Li Qian , Liao Sha , Zhao Xinfeng , Zheng Xiaohui
Published: November 2016

Drug–protein interaction analysis has become a considerable topic in life science which includes clarifying protein functions, explaining drug action mechanisms and uncovering novel drug candidates. This work was to determine the association constants (KA) of six drugs to β2‐adrenergic receptor by injection amount‐dependent method using stationary phase containing the immobilized receptor. The values of KA were calculated to be (25.85 ± 0.035) × 104 m−1 for clorprenaline, (42.51 ± 0.054) × 104 m−1 for clenbuterol, (6.67 ± 0.008) × 104 m−1 for terbutaline, (33.99 ± 0.025) × 104 m−1 for tulobuterol, (7.59 ± 0.011) × 104 m−1 for salbutamol and (78.52 ± 0.087) × 104 m−1 for bambuterol. This rank order agreed well with the data determined by zonal elution, frontal analysis and nonlinear chromatography, even using different batches of β2‐AR column. A good correlation was found between the association constants by the current method and radio‐ligand binding assay. Our data indicates that the injection amount‐dependent method is a powerful alternative for rapid analysis of ligand–receptor interactions.
An In‐situ glucose‐stimulated insulin secretion assay under perfusion bioreactor conditions
Authors: Sharp Jamie , Vermette Patrick
Published: November 2016

Perfusion bioreactors, unlike traditional in vitro cell culture systems, offer stringent control of physiological parameters such as pH, flow, temperature, and dissolved oxygen concentration which have been shown to have an impact on cellular behaviour and viability. Due to the relative infancy and the growing interest in these in vitro culture systems, detection methods to monitor cell function under dynamic perfusion bioreactor conditions remains one of the main challenges. In this study, INS‐1 cells, a cell line which exhibit glucose‐stimulated insulin secretion, were embedded in fibrin and cultured under perfusion bioreactor conditions for 48 h and then exposed to either a high‐, or low‐glucose concentration for 24 h. These cultures were compared to non‐bioreacted controls. Bioreacted cultures exposed to a high‐glucose concentration showed the highest glucose‐stimulated insulin secretion when compared to those in a low‐glucose environment. The stimulation index, a marker for insulin secretion functionality, increased over time. A lower incidence of apoptotic cells was observed in the bioreacted cultures when compared to non‐bioreacted ones, as evaluated by a TUNEL assay. Immunofluorescence staining of Ki67 and insulin was performed and showed no differences in the incidence of proliferative cells between conditions (bioreacted and non‐bioreacted), where all cells stained positive for insulin. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:454–462, 2017
N‐methyl‐N‐nitrosourea induces retinal degeneration in the rat via the inhibition of NF‐κB activation
Authors: Xiong Yu , Ji Hong‐pei , Song Wei‐tao , Yin Ye‐Wei , Xia Chao‐hua , Xu Bei , Xu Yi , Xia Xiao‐bo
Published: November 2016

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by the loss of photoreceptor cells through apoptosis. N‐methyl‐N‐nitrosourea (MNU) is an alkylating toxicant that induces photoreceptor cell death resembling hereditary RP. This study aimed to investigate the role of nuclear factor κB (NF‐κB) in MNU‐induced photoreceptor degeneration. Adult rats received a single intraperitoneal injection of MNU (60 mg/kg bodyweight). Hematoxylin and eosin staining demonstrated progressive outer nuclear layer (ONL) loss after MNU treatment. Transmission electron microscopy revealed nuclear pyknosis, chromatin margination in the photoreceptors, increased secondary lysosomes, and lobulated retinal‐pigmented epithelial cells in MNU‐treated rats. Numerous photoreceptor cells in the ONL showed positive TUNEL staining and apoptosis rate peaked at 24 hours. Enhanced depth imaging spectral‐domain optical coherence tomography showed ONL thinning and decreased choroid thickness. Electroretinograms showed decreased A wave amplitude that predominated in scotopic conditions. Western blot analysis showed that nuclear IκBα level increased, whereas nuclear NF‐κB p65 decreased significantly in the retinas of MNU‐treated rats. These findings indicate that MNU leads to selective photoreceptor degradation, and this is associated with the inhibition of NF‐κB activation.
Copper is a Cofactor of the Formylglycine‐Generating Enzyme
Authors: Knop Matthias , Dang Thanh Quy , Jeschke Gunnar , Seebeck Florian P.
Published: November 2016

Formylglycine‐generating enzyme (FGE) is an O2‐utilizing oxidase that converts specific cysteine residues of client proteins to formylglycine. We show that CuI is an integral cofactor of this enzyme and binds with high affinity (KD=of 10−17 m) to a pair of active‐site cysteines. These findings establish FGE as a novel type of copper enzyme.
Does minimalist transfemoral transcatheter aortic valve replacement produce better survival in patients with severe chronic obstructive pulmonary disease?
Authors: Condado Jose F. , Haider Moosa N. , Lerakis Stamatios , Keegan Patricia , Caughron Hope , Thourani Vinod H. , Devireddy Chandan , Leshnower Bradley , Mavromatis Kreton , Sarin Eric L. , Stewart James , Guyton Robert , Forcillo Jessica , Patel Ateet , Simone Amy , Block Peter C. , Babaliaros Vasilis
Published: November 2016

Objectives

To compare outcomes after minimalist and standard transfemoral transcatheter aortic valve replacement (TF‐TAVR) in patients with severe chronic obstructive pulmonary disease (COPD).

Background

TF‐TAVR is increasingly performed with conscious sedation and transthoracic echocardiography guidance (minimalist). The safety/efficacy of this technique in patients with severe COPD is unknown.

Methods

We compared demographics, 30‐day outcomes and 1‐year survival of patients with severe COPD (FEV1% ≤50) who underwent minimalist vs. standard TF‐TAVR between 2008 and 2015 at our institution.

Results

Of 88 patients with severe COPD, 46 underwent minimalist and 42 underwent standard TF‐TAVR. There were no differences on baseline characteristics, except for more history of coronary artery bypass grafting (45.5% vs. 20.6%, P = 0.03) and less history of cerebrovascular disease (16.7% vs. 45.5%, P = 0.03) in the standard TF‐TAVR. Seventeen minimalist TF‐TAVR patients (41.0%) were transferred directly to the general medical ward with telemetry monitoring (without ICU stay); all standard TF‐TAVR patients went to the ICU. Minimalist TF‐TAVR patients had shorter procedure time (97 vs. 129 min, P < 0.001), ICU time (21.8 vs. 29.8 hr, P = 0.001) and length of stay (2 vs. 5 days, P = 0.001). There were no differences in procedure complications and 30‐day mortality between groups. In our multivariate analysis, minimalist TF‐TAVR (HR 0.28, 95%CI 0.08–0.97) and previous coronary revascularization (HR 0.24, 95%CI 0.09–0.65) were associated with increased 1‐year survival. In contrast, moderate paravalvular leak (HR 7.73, 95%CI 1.94–30.84) was associated with decreased 1‐year survival.

Conclusion

In patients with severe COPD, Minimalist TF‐TAVR results in less resource utilization and improved 1‐year survival compared to standard approach. Our findings should be validated in a larger cohort of patients with severe COPD. © 2016 Wiley Periodicals, Inc.
Stenting of the ductus arteriosus in infants with functionally univentricular heart disease and ductal‐dependent pulmonary blood flow: A single‐center experience
Authors: Celebi Ahmet , Yucel Ilker Kemal , Bulut Mustafa Orhan , Kucuk Mehmet , Balli Sevket
Published: November 2016

Objective

To determine the short‐ and medium‐term outcomes of ductal stenting (DS) in patients with functionally univentricular hearts (FUHs) and ductal‐dependent pulmonary blood flow.

Background

Several studies have evaluated the outcomes of DS in a limited number of patients with FUHs. Nonetheless, there is still no consensus regarding the indications for this procedure, and no appropriate patient selection criteria have been devised.

Methods

From 2005 to 2015, cardiac catheterization for DS was performed in 68 patients with FUHs. Of these patients, 49 had single source pulmonary blood flow from ductus arteriosus. Procedural and follow‐up data were evaluated.

Results

The median weight of the patients was 3.6 kg (2.3–6.8 kg), and the median age was 26 days (3 days–8 months). The technical success rate of the procedure was 95% (65 of 68 patients). Mean oxygen saturation increased from 70% ± 7.6% to 87% ± 4.6% (P < 0.0001). Among patients in whom DS was successful, 55 (84.6%) were bridged to a Glenn procedure after a median of 9.1 months (6.4–14 months), and 41 (63%) were successfully bridged to a Glenn procedure without additional interventions. Of the 16 patients with preexisting mild pulmonary artery stenosis, five required a surgical shunt due to progressive branch pulmonary artery stenosis, while nine were bridged to a Glenn operation without shunt placement. Five (7.3%) patients died, including patients who were sent to surgery.

Conclusion

DS is a reasonable and effective alternative to surgical shunt placement as a first‐stage palliative procedure in patients with FUHs. © 2016 Wiley Periodicals, Inc.
Transcatheter closure of large atrial septal defects using 40 mm amplatzer septal occluder: Single group experience with short and intermediate term follow‐up
Authors: Dalvi Bharat , Sheth Kshitij , Jain Shreepal , Pinto Robin
Published: November 2016

Objectives

To assess feasibility, safety, and efficacy of the use of 40 mm Amplatzer septal occluder (ASO 40) for the closure of large atrial septal defects (ASD).

Background

There is very little data available on closure of large ASDs with ASO 40.

Materials and methods

Case records of patients who underwent ASD closure with ASO 40 between 2002 and 2014 were retrospectively analyzed. All patients had clinical, transthoracic, and transesophageal echocardiographic (TEE) evaluation prior to device closure. Postclosure follow‐up was done at 6 weeks, 6 months, and annually thereafter.

Results

87 patients underwent ASD closure using ASO 40 during the study period. Mean age and weight of the group was 32.4 ± 11.6 years and 59.5 ± 11.3 kg respectively. Mean ASD diameter on TEE was 32 ± 2.8 mm. The balloon stretched diameter (N = 40) was 37.8 ± 1.3 mm. The balloon assisted technique was used in 80/87 patients for device deployment. The procedure was successful in 84/87 patients. Follow‐up was available in 77 patients over a period of 44 ± 15.7 months. 3/77 patients had a small residual shunt. The severity of tricuspid regurgitation decreased in 40/77 patients. The pulmonary artery systolic pressure decreased from 49.7 ± 9.2 to 41.2 ± 6.2 mm Hg (N = 61; P < 0.05). The right ventricular diameter decreased from 35.1 ± 2.8 to 26.1 ± 3 mm (N = 77; P < 0.05).

Conclusion

ASO 40 can be used safely and effectively with promising short and intermediate term results.© 2016 Wiley Periodicals, Inc.
Does direct stenting with drug‐eluting stents improve outcome? A meta‐analysis of 10,900 patients
Authors: Magalhaes Marco A. , Minha Sa'ar , Lhermusier Thibault , Pendyala Lakshmana , Escarcega Ricardo O. , Baker Nevin C. , Torguson Rebecca , Satler Lowell F. , Pichard Augusto , Waksman Ron
Published: November 2016

Objectives

The aim of this study is to summarize the outcomes of patients undergoing direct stenting (DS) with drug‐eluting stents (DES) compared to those who underwent balloon predilatation.

Background

DS has been associated with improved outcomes in the bare‐metal stent era. Although DS with DES implantation has been increasingly adopted in clinical practice, its safety and effectiveness remain controversial.

Methods

The search criteria identified 546 studies in the Medline/PubMed, Cochrane, and EMBASE databases from 2001 to July 2014. From these, seven studies totaling 10,900 patients were selected. Summarized estimates [odds ratio (OR) and 95% confidence intervals] were obtained using a random‐effects model. The primary outcomes were a composite of major adverse cardiac events (MACE), including all‐cause death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included a composite of death and MI and the rates of target lesion revascularization (TLR).

Results

Overall, 4101 (38%) and 6799 (62%) patients underwent DS with DES and balloon pre‐dilatation, respectively. DS with DES reduced the likelihood of MACE (OR: 0.81 [0.71–0.93]). Additionally, DS with DES was associated with reduced rates of death/MI (OR: 0.76 [0.62–0.92]), and TLR (OR: 0.66 [0.44–0.98]).

Conclusions

DS with DES is safe and may be associated with better outcomes in selected patients. © 2016 Wiley Periodicals, Inc.
Effect of Post‐Treatment on Structure and Catalytic Activity of CuCo‐based Materials for Glycerol Oxidation
Authors: Dodekatos Georgios , Tüysüz Harun
Published: November 2016

A series of CuCo‐based materials prepared by co‐precipitation with varied Co/Cu ratios and different post‐treatments were applied in the selective oxidation of glycerol in the aqueous phase under basic conditions. The influence of the post‐treatment on the structure of the materials and the catalytic performance was investigated in detail. As‐prepared materials without calcination and materials calcined under air with subsequent reduction under ethanol/N2 gas stream showed higher conversion of glycerol compared to samples solely calcined under air or to samples calcined under air with subsequent reduction under H2/Ar gas stream. The main products identified in the liquid phase were glyceric, glycolic, and formic acids. Systematic catalytic studies for differently prepared samples with varied Cu content and subsequent characterization of the materials by N2 physisorption, XRD, TEM, and EDX allowed for the identification of CoO(OH) in contact with CuO as the potentially active phases.
Reinventing Hsp90 Inhibitors: Blocking C‐Terminal Binding Events to Hsp90 by Using Dimerized Inhibitors
Authors: Koay Yen Chin , Wahyudi Hendra , McAlpine Shelli R.
Published: November 2016

Heat shock protein 90 (Hsp90) is a molecular chaperone (90 kDa) that functions as a dimer. This protein facilitates the folding, assembly, and stabilization of more than 400 proteins that are responsible for cancer development and progression. Inhibiting Hsp90’s function will shut down multiple cancer‐driven pathways simultaneously because oncogenic clients rely heavily on Hsp90, which makes this chaperone a promising anticancer target. Classical inhibitors that block the binding of adenine triphosphate (ATP) to the N‐terminus of Hsp90 are highly toxic to cells and trigger a resistance mechanism within cells. This resistance mechanism comprises a large increase in prosurvival proteins, namely, heat shock protein 70 (Hsp70), heat shock protein 27 (Hsp27), and heat shock factor 1 (HSF‐1). Molecules that modulate the C‐terminus of Hsp90 are effective at inducing cancer‐cell death without activating the resistance mechanism. Herein, we describe the design, synthesis, and biological binding affinity for a series of dimerized C‐terminal Hsp90 modulators. We show that dimers of these C‐terminal modulators synergistically inhibit Hsp90 relative to monomers.
A Synthetic Toolbox for the In Situ Formation of Functionalized Homo‐ and Heteropolysaccharide‐Based Hydrogel Libraries
Authors: Dibbert Nick , Krause Andreas , Rios‐Camacho Julio‐Cesar , Gruh Ina , Kirschning Andreas , Dräger Gerald
Published: November 2016

A synthetic toolbox for the introduction of aldehydo and hydrazido groups into the polysaccharides hyaluronic acid, alginate, dextran, pullulan, glycogen, and carboxymethyl cellulose and their use for hydrogel formation is reported. Upon mixing differently functionalized polysaccharides derived from the same natural precursor, hydrazone cross‐linking takes place, which results in formation of a hydrogel composed of one type of polysaccharide backbone. Likewise, hydrogels based on two different polysaccharide strands can be formed after mixing the corresponding aldehydo‐ and hydrazido‐modified polysaccharides. A second line of these studies paves the way to introduce a biomedically relevant ligand, namely, the adhesion factor cyclic RGD pentapeptide, by using an orthogonal click reaction. This set of modified polysaccharides served to create a library of hydrogels that differ in the combination of polysaccharide strands and the degree of cross‐linking. The different hydrogels were evaluated with respect to their rheological properties, their ability to absorb water, and their cytotoxicity towards human fibroblast cell cultures. None of the hydrogels studied were cytotoxic, and, hence, they are in principal biocompatible for applications in tissue engineering.
Hydrogenated Bismuth Molybdate Nanoframe for Efficient Sunlight‐Driven Nitrogen Fixation from Air
Authors: Hao Yuchen , Dong Xiaoli , Zhai Shangru , Ma Hongchao , Wang Xiuying , Zhang Xiufang
Published: November 2016

Sunlight‐driven dinitrogen fixation can lead to a novel concept for the production of ammonia under mild conditions. However, the efficient artificial photosynthesis of ammonia from ordinary air (instead of high pure N2) has never been implemented. Here, we report for the first time the intrinsic catalytic activity of Bi2MoO6 catalyst for direct ammonia synthesis under light irradiation. The edge‐exposed coordinatively unsaturated Mo atoms in an Mo−O coordination polyhedron can act as activation centers to achieve the chemisorption, activation, and photoreduction of dinitrogen efficiently. Using that insight as a starting point, through rational structure and defect engineering, the optimized Bi2MoO6 sunlight‐driven nitrogen fixation system, which simultaneously possesses robust nitrogen activation ability, excellent light‐harvesting performance, and efficient charge transmission was successfully constructed. As a surprising achievement, this photocatalytic system demonstrated for the first time ultra‐efficient (1.3 mmol g−1 h−1) and stable sunlight‐driven nitrogen fixation from air in the absence of any organic scavengers.
Epicocconone–Hemicyanine Hybrids: Near Infrared Fluorophores for Protein Staining and Cell Imaging
Authors: Karuso Peter , Loa Kum Cheung Wendy , Peixoto Philippe A. , Boulangé Agathe , Franck Xavier
Published: November 2016

The development of new near infrared (NIR) dyes is crucial for diverse applications and especially bioimaging, as they absorb and emit light in the “therapeutic window“ (650–950 nm). We report here a new family of NIR fluorophores that has been obtained by hybridising hemicyanines with epicocconone. Emission wavelengths of these hybrid dyes is in the range 715–795 nm and is combined with large Stokes’ shifts (75–95 nm). The absorption and emission wavelength can be modulated according to the hemicyanine moiety and adding sulfonic acid moieties enhances water solubility. We demonstrate their application in the sensitive detection of proteins in gel electrophoresis and the staining of specific cellular organelles in confocal microscopy. These results are particularly encouraging and bring forward a new fluorescent skeleton for chemical biology.
Radical Reaction Control in the AdoMet Radical Enzyme CDG Synthase (QueE): Consolidate, Destabilize, Accelerate
Authors: Jäger Christof M. , Croft Anna K.
Published: November 2016

Controlling radical intermediates and thus catalysing and directing complex radical reactions is a central feature of S‐adensosylmethionine (SAM)‐dependent radical enzymes. We report ab initio and DFT calculations highlighting the specific influence of ion complexation, including Mg2+, identified as a key catalytic component on radical stability and reaction control in 7‐carboxy‐7‐deazaguanine synthase (QueE). Radical stabilisation energies (RSEs) of key intermediates and radical clock‐like model systems of the enzyme‐catalysed rearrangement of 6‐carboxytetrahydropterin (CPH4), reveals a directing role of Mg2+ in destabilising both the substrate‐derived radical and corresponding side reactions, with the effect that the experimentally‐observed rearrangement becomes dominant over possible alternatives. Importantly, this is achieved with minimal disruption of the thermodynamics of the substrate itself, affording a novel mechanism for an enzyme to both maintain binding potential and accelerate the rearrangement step. Other mono and divalent ions were probed with only dicationic species achieving the necessary radical conformation to facilitate the reaction.
Hydroxyapatite Nanowires@Metal–Organic Framework Core/Shell Nanofibers: Templated Synthesis, Peroxidase‐Like Activity, and Derived Flexible Recyclable Test Paper
Authors: Chen Fei‐Fei , Zhu Ying‐Jie , Xiong Zhi‐Chao , Sun Tuan‐Wei
Published: November 2016

The templated synthesis of hydroxyapatite (HAP) nanowires@metal–organic framework (MOF) core/shell nanofibers (named HAP@MIL‐100(Fe) nanofibers) is demonstrated. The ultralong hydroxyapatite nanowires are adopted as a hard template for the nucleation and growth of MIL‐100(Fe) (a typical MOF) through the layer‐by‐layer method. The Coulombic and chelation interactions between Ca2+ ions on the surface of the HAP nanowires and the COO− organic linkers of MIL‐100(Fe) play key roles in the formation process. The as‐prepared, water‐stable HAP@MIL‐100(Fe) nanofibers exhibit peroxidase‐like activity toward the oxidation of different peroxidase substrates in the presence of H2O2, accompanied by a clear color change of the solution. Furthermore, a flexible, recyclable HAP@MIL‐100(Fe) test paper is prepared successfully by using HAP@MIL‐100(Fe) nanofibers as building blocks. A simple, low‐cost, and sensitive colorimetric method for the detection of H2O2 and glucose is established based on the as‐prepared, flexible, recyclable HAP@MIL‐100(Fe) test paper. More importantly, the HAP@MIL‐100(Fe) test paper can be recovered easily for reuse by simply dipping in absolute ethanol for just 30 min, thus showing excellent recyclability. With its combination of advantages such as easy transportation, easy storage and use, rapid recyclability, light weight, and high flexibility, this HAP@MIL‐100(Fe) test paper is promising for wide applications in various fields.
Multicomponent Aqueous Synthesis of Iodo‐1,2,3‐triazoles: Single‐Step Models for Dual Modification of Free Peptide and Radioactive Iodo Labeling
Authors: Li Lingjun , Ding Shengqiang , Yang Yanping , Zhu Anlian , Fan Xincui , Cui Mengchao , Chen Changpo , Zhang Guisheng
Published: November 2016

Iodo‐1,2,3‐triazoles are of considerable interest for chemical and biomedical applications. However, current synthetic methods for preparing iodo‐1,2,3‐triazoles cannot easily be applied to the direct modification of bioactive molecules in water. Through the combination of water‐compatible oxidative iodination and the copper‐catalyzed alkyne–azide cycloaddition reaction, a novel copper‐catalyzed aqueous multicomponent synthetic method for the preparation of 5‐iodo‐1,2,3‐triazoles has been developed. The method is highly effective and selective for substrates including biologically relevant compounds with nucleoside, sugar, and amino acid moieties. Based on this aqueous tandem reaction, a direct single‐step multicomponent dual modification of peptide is developed from readily available starting materials. Furthermore, the method could also be applied to concise and fast multicomponent radioactive 125I labeling from an aqueous solution of commercially available sodium 125iodide as a starting material.
Enantioselective Synthesis of N−H‐Free 1,5‐Benzothiazepines
Authors: Wang Guojin , Tang Yu , Zhang Yu , Liu Xiaohua , Lin Lili , Feng Xiaoming
Published: November 2016

An enantioselective sulfa‐Michael‐cyclization reaction was developed for the synthesis of 1,5‐benzothiazepines with versatile pharmacological activities. The reaction between 2‐aminothiophenol and α,β‐unsaturated pyrazoleamides gave direct access to N−H‐free 1,5‐benzothiazepines in the presence of a chiral N,N′‐dioxide/Yb(OTf)3 complex. Excellent enantioselectivities (up to 96 % ee) and high yields (up to 99 %) were obtained for a broad range of substrates under mild reaction conditions. This method provided a facile approach to the antidepressant drug (R)‐(−)‐Thiazesim.
Effects of solvent on inclusion complexation of a chiral dipeptide toward racemic BINOL
Authors: Hu Xiaoyun , Yang Yuyuan , Shi Shuai , Shan Zixing
Published: November 2016

The effects of reaction solvent on inclusion complexation of a chiral dipeptide (3S,6S)‐1 derived from (S)‐proline toward racemic BINOL was investigated, discovering that the reaction solvent played a crucial role in determining the inclusion complexation behavior of dipeptide (3S,6S)‐1 toward rac‐BINOL. (3S,6S)‐1 did not show any chiroselective or achiroselective complexation toward rac‐BINOL in polar protic solvents such as methanol and ethanol, polar aprotic solvents including trichloromethane and THF, while in polar aprotic solvent ethyl acetate and apolar aprotic solvents benzene, (3S,6S)‐1 displayed achiroselective complexation toward rac‐BINOL. However, the resulting heterocomplex HC‐2 from benzene and HC‐3 from ethyl acetate have a different composition. Single crystal X‐ray diffraction analysis demonstrates that the two heterocomplexes are formed via different H‐bond interaction patterns, in which the reaction solvent has a dramatic effect. Furthermore, this work provides a relatively green method for quantitative enantiomeric enrichment of nonracemic BINOL, in which unacceptable and toxic benzene was replaced by ethyl acetate.
Trends in hospitalization for congestive heart failure, 1996–2009
Authors: Munir Muhammad Bilal , Sharbaugh Michael S. , Thoma Floyd W. , Nisar Muhammad Umer , Kamran Amir S. , Althouse Andrew D. , Saba Samir
Published: November 2016

Background

Although heart failure (HF) is a common cause of hospital admissions, few data describe temporal trends in HF hospitalization. We present data on number of HF admissions, length of stay (LOS), and inpatient mortality in the United States, 1996–2009.

Hypothesis

To assess HF hospitalizations in a national sample of United States population.

Methods

Data were obtained from the National Hospital Discharge Survey (NHDS), a national probability sample survey of discharges conducted annually by the National Center for Health Statistics. Sampling weights are applied to raw NHDS data to produce national estimates. Hospitalizations with a primary diagnosis of HF were identified using ICD‐9‐CM codes. We excluded hospitalizations where HF was a secondary diagnosis. Weighted least squares regression was used to test for linear trends in HF hospitalizations.

Results

Approximately 15.5 million weighted primary HF hospitalizations were included. The number of total primary HF hospitalizations increased from 1 000 766 in 1996 to about 1 173 832 in 2009 (β = 7371 hospitalizations per year; 95% confidence interval (CI): 552 to 14 190, P = 0.036). Mean LOS per hospitalization decreased from 6.07 days in 1996 to about 5.26 days in 2009 (β = −0.059 days per year; 95% CI: −0.079 to −0.039, P < 0.001). Inpatient mortality rates declined from 4.92% in 1996 to 3.41% in 2009 (β = −0.17% per year; 95% CI: −0.23 to −0.10, P < 0.001).

Conclusions

In a nationally representative sample of HF hospitalizations, mean LOS and inpatient mortality rates declined over the past 2 decades. HF management cost is most likely to be reduced by decreasing the number of HF admissions.
Computational simulation of formin‐mediated actin polymerization predicts homologue‐dependent mechanosensitivity
Authors: Bryant Derek , Clemens Lara , Allard Jun
Published: November 2016

Many actin structures are nucleated and assembled by the barbed‐end tracking polymerase formin family, including filopodia, focal adhesions, the cytokinetic ring and cell cortex. These structures respond to forces in distinct ways. Formins typically have profilin‐actin binding sites embedded in highly flexible disordered FH1 domains, hypothesized to diffusively explore space to rapidly capture actin monomers for delivery to the barbed end. Recent experiments demonstrate that formin‐mediated polymerization accelerates when under tension. The acceleration has been attributed to modifying the state of the FH2 domain of formin. Intriguingly, the same acceleration is reported when tension is applied to the FH1 domains, ostensibly pulling monomers away from the barbed end. Here we develop a mesoscale coarse‐grain model of formin‐mediated actin polymerization, including monomer capture and delivery by FH1, which sterically interacts with actin along its entire length. The binding of actin monomers to their specific sites on FH1 is entropically disfavored by the high disorder. We find that this penalty is attenuated when force is applied to the FH1 domain by revealing the binding site, increasing monomer capture efficiency. Overall polymerization rates can decrease or increase with increasing force, depending on the length of FH1 domain and location of binding site. Our results suggest that the widely varying FH1 lengths and binding site locations found in known formins could be used to differentially respond to force, depending on the actin structure being assembled. © 2016 Wiley Periodicals, Inc.
Responding to the quality imperative to embed mental health care into ambulatory oncology
Authors: Penedo Frank J. , Cella David
Published: November 2016

The calls by the Institute of Medicine to fully integrate psychosocial care into oncology practice are closer to being implemented. Because of the multiple challenges faced across the cancer care continuum, it is recommended that multidimensional approaches that extend beyond the assessment of depression and anxiety and consider physical symptoms and practical concerns be considered as part of systematic psychosocial screening in oncology practice. See also pages 485–93.
What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study
Authors: Rungruang Bunja J. , Miller Austin , Krivak Thomas C. , Horowitz Neil S. , Rodriguez Noah , Hamilton Chad A. , Backes Floor J. , Carson Linda F. , Friedlander Michael , Mutch David G. , Goodheart Michael J. , Tewari Krishnansu S. , Wenham Robert M. , Bookman Michael A. , Maxwell G. Larry , Richard Scott D.
Published: November 2016

BACKGROUND

The purpose of this study was to determine the effect of retroperitoneal (RP) exploration on progression‐free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC) patients with stage IIIC disease who underwent optimal debulking surgery.

METHODS

Data were collected from records of the Gynecologic Oncology Group 182 (GOG‐182) study of stage IIIC EOC patients cytoreduced to no gross residual disease (R0) or minimal gross residual (<1 cm) disease (MGRD) at primary surgery. Patients with stage IIIC disease by intraperitoneal (IP) tumor were included and divided into 3 groups: 1) > 2 cm IP tumor without lymph node involvement (IP/RP−), 2) > 2 cm IP tumor with lymph node involvement (IP/RP+), and 3) > 2 cm IP tumor with no RP exploration (IP/RP?). The effects of disease distribution and RP exploration on PFS and OS were assessed using Kaplan–Meier and proportional hazards methods.

RESULTS

There were 1871 stage IIIC patients in GOG‐182 who underwent optimal primary debulking surgery. Of these, 689 (36.8%) underwent RP exploration with removal of lymph nodes from at least 1 para‐aortic site, and 1182 (63.2%) did not. There were 269 patients in the IP/RP− group, 420 patients in the IP/RP + group, and 1182 patients in the IP/RP? group. Improved PFS (18.5 vs 16.0 months; P < .0001) and OS (53.3 vs 42.8 months; P < .0001) were associated with RP exploration versus no exploration. Patients with MGRD had improved PFS (16.8 vs 15.1 months, P = 0.0108) and OS (44.9 vs 40.5 months, P = 0.0076) versus no exploration.

CONCLUSIONS

RP exploration at the time of primary surgery in patients with optimally debulked stage IIIC EOC is associated with a survival benefit. Cancer 2017;123:985–93. © 2016 American Cancer Society.
Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single‐center, open‐label, phase 2 study
Authors: Gulhati Pat , Raghav Kanwal , Shroff Rachna T. , Varadhachary Gauri R. , Kopetz Scott , Javle Milind , Qiao Wei , Wang Huamin , Morris Jeffrey , Wolff Robert A. , Overman Michael J.
Published: November 2016

BACKGROUND

Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX.

METHODS

In this phase 2, single‐arm, single‐center, open‐label study, patients aged ≥18 years with untreated, advanced SBA or AAC were recruited. Patients received capecitabine at a dose of 750 mg/m2 orally twice daily on days 1 to 14, oxaliplatin at a dose of 130 mg/m2 intravenously on day 1, and bevacizumab at a dose of 7.5 mg/kg intravenously on day 1 of a 21‐day cycle. The primary endpoint was progression‐free survival (PFS) at 6 months. Secondary objectives included response rate, overall PFS, overall survival, and toxicity.

RESULTS

Between August 2011 and November 2014, a total of 30 patients were enrolled into the study (male/female ratio of 13/17; median age of 63 years [range, 33‐78 years]; and 7 patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 0, 20 patients with an ECOG PS of 1, and 3 patients with an ECOG PS of 2). Of the 30 patients, 23 (77%) had SBA (18 of duodenal origin and 5 of jejunal/ileal origin) and 7 patients (23%) had AAC (5 of pancreaticobiliary subtype, 1 of mixed subtype, and 1 of intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 patients each [23%]), neutropenia (6 patients [20%]), and diarrhea (3 patients [10%]) (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The probability of PFS at 6 months was 68% (95% confidence interval [95% CI], 52% to 88%). The response rate was 48.3%, with 1 complete response and 13 partial responses; 10 patients achieved stable disease. At a median follow‐up of 25.9 months, the median PFS was 8.7 months (95% CI, 4.9‐10.5 months) and the median overall survival was 12.9 months (95% CI, 9.2‐19.7 months).

CONCLUSIONS

The results of the current study indicate that CAPOX with bevacizumab is an active and well‐tolerated regimen for patients with SBA and AAC. These findings support the need for further investigation into the clinical benefit of targeting angiogenesis in patients with SBA and AAC. Cancer 2017;123:1011–17. © 2016 American Cancer Society.
Wire‐Active Microrheology to Differentiate Viscoelastic Liquids from Soft Solids
Authors: Loosli Frédéric , Najm Matthieu , Chan Raymond , Oikonomou Evdokia , Grados Arnaud , Receveur Mathieu , Berret Jean‐François
Published: November 2016

Viscoelastic liquids are characterized by a finite static viscosity and a yield stress of zero, whereas soft solids have an infinite viscosity and a non‐zero yield stress. The rheological nature of viscoelastic materials has long been a challenge and is still a matter of debate. Here, we provide for the first time the constitutive equations of linear viscoelasticity for magnetic wires in yield‐stress materials, together with experimental measurements by using magnetic rotational spectroscopy (MRS). In MRS, the wires were subjected to a rotational magnetic field as a function of frequency and the motion of the wire was monitored by using time‐lapse microscopy. The studied soft solids were aqueous dispersions of gel‐forming polysaccharide (gellan gum) at concentrations above the gelification point. It was found that soft solids exhibited a clear and distinctive signature compared with viscous and viscoelastic liquids. In particular, the average wire rotation velocity equaled zero over a broad frequency range. We also showed that the MRS technique is quantitative. The equilibrium elastic modulus was retrieved from the wire oscillation amplitudes, and agrees with polymer‐dynamics theory.