bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, characterization, and in vitro effect of the Cu(II) complex with niflumic acid and 3‐picoline on paraoxanase‐I
Authors: Dilek Esra , Caglar Sema , Çardak Seda , Karakoç Barış , Caglar Bülent , Sahin Onur
Published: May 2019

Niflumic acid is used to treat inflammatory rheumatoid diseases, pain, and fever. The present study reports the experimental, spectroscopic, thermal, structural analyses, and biological activities of this complex. The nonsteroidal anti‐inflammatory drug niflumic acid, 3‐picoline, and copper(II) chloride were utilized to synthesize a new complex: [Cu2Cl
2(nif)
2(3‐pic)
4]. The crystal structure of [Cu
2Cl
2(nif)
2(3‐pic)
4] was determined by X‐ray crystallography. The complex crystallizes in the triclinic space group P‐1 and each Cu(II) center displayed six‐coordinated distorted octahedral geometry. Two Cu(II) centers are connected by a chloro‐bridge to form the binuclear metal core. Finally, the in vitro effects of the synthesized new complex and free niflumic acid were evaluated on the human serum paraoxonase 1 enzyme. At low doses, both the new complex and free niflumic acid showed very good inhibition activity with different inhibition mechanisms. In addition, the results showed that the new complex has more inhibition activity than free niflumic acid.
Multi‐omics profiling of CHO parental hosts reveals cell line‐specific variations in bioprocessing traits
Authors: Lakshmanan Meiyappan , Kok Yee Jiun , Lee Alison P. , Kyriakopoulos Sarantos , Lim Hsueh Lee , Teo Gavin , Poh Swan Li , Tang Wen Qin , Hong Jongkwang , Tan Andy Hee‐Meng , Bi Xuezhi , Ho Ying Swan , Zhang Peiqing , Ng Say Kong , Lee Dong‐Yup
Published: May 2019

Chinese hamster ovary (CHO) cells are the most prevalent mammalian cell factories for producing recombinant therapeutic proteins due to their ability to synthesize human‐like post‐translational modifications and ease of maintenance in suspension cultures. Currently, a wide variety of CHO host cell lines has been developed; substantial differences exist in their phenotypes even when transfected with the same target vector. However, relatively less is known about the influence of their inherited genetic heterogeneity on phenotypic traits and production potential from the bioprocessing point of view. Herein, we present a global transcriptome and proteome profiling of three commonly used parental cell lines (CHO‐K1, CHO‐DXB11, and CHO‐DG44) in suspension cultures and further report their growth‐related characteristics, and N‐ and O‐glycosylation patterns of host cell proteins (HCPs). The comparative multi‐omics and subsequent genome‐scale metabolic network model‐based enrichment analyses indicated that some physiological variations of CHO cells grown in the same media are possibly originated from the genetic deficits, particularly in the cell‐cycle progression. Moreover, the dihydrofolate reductase deficient DG44 and DXB11 possess relatively less active metabolism when compared to K1 cells. The protein processing abilities and the N‐ and O‐glycosylation profiles also differ significantly across the host cell lines, suggesting the need to select host cells in a rational manner for the cell line development on the basis of recombinant protein being produced.
How to choose proper local treatment in men aged ≥75 years with cT2 localized prostate cancer?
Authors: Jin Kun , Qiu Shi , Li Jiakun , Zheng Xiaonan , Tu Xiang , Liao Xinyang , Yang Yan , Yang Lu , Wei Qiang
Published: May 2019

Background

For localized prostate cancer (PCa), radical prostatectomy (RP) and radiotherapy (RT) are two standard interventions to decrease PCa mortality. Contemporary studies contained the elderly people; analyses focusing on patients over 75 years of age were still lacking.

Method

In the Surveillance Epidemiology and End Results (SEER) database (2004‐2015), people over 75 years of age with cT2 stage were selected in our research. Multivariable Cox proportional hazard models were used to analyze cancer‐specific mortality (CSM) and overall mortality (OM) after adjustment. The propensity score matching was performed to assume the randomization. An instrument variate (IVA) was used to calculate the unmeasured confounders.

Results

Radical prostatectomy is superior to RT in OM and CSM after adjustment for covariates (HR = 0.54, 95% CI = 0.47‐0.62, P < 0.001 and HR = 0.30, 95% CI = 0.20‐0.45, P < 0.001, respectively). The cox model after matching indicated similar consequence (OM: HR = 0.53, 95% CI = 0.46‐0.62, P < 0.001; CSM: HR = 0.27, 95% CI = 0.17‐0.43, P < 0.001). In the IVA‐adjusted model, the effect of treatment changed slightly (OM: HR = 0.65, 95% CI = 0.54‐0.78, P < 0.001; CSM: HR = 0.21, 95% CI = 0.12‐0.37, P < 0.001). Subgroup analyses showed that for patients with GS = 7, those received RP obtained the highest risk decline for overall death (HR = 0.41, 95% CI = 0.32‐0.52); and for patients with younger age, those received RP obtained the highest risk decline for CSM (HR = 0.11, 95% CI = 0.01‐0.52).

Conclusion

Patients over 75 years of age with cT2 stage will obtain more benefit from RP compared with RT, especially for patients with GS = 7 and younger age.
Single‐step Conversion of Methyl Ethyl Ketone to Olefins over ZnxZryOz Catalysts in Water
Authors: Dagle Vanessa L. , Dagle Robert A. , Kovarik Libor , Baddour Frederick , Habas Susan E. , Elander Richard
Published: May 2019

In this study we investigated the conversion of aqueous methyl‐ethyl‐ketone (MEK) to olefin fuel precursors over ZnxZryOz mixed oxide catalysts. Experiments were carried out in water as MEK is intended to be produced from the dehydration of 2,3‐butanediol in fermentation broth which is highly diluted in water. We demonstrated that ZnxZryOz catalysts are highly effective for converting aqueous MEK to C4−C5 olefins. High selectivity to olefins equal to 85 % was reached at 92 % per pass conversion when under H2 atmosphere. Catalyst stability was demonstrated for 60 hours’ time on stream, highlighting the potential for upgrading 2,3‐butanediol contained in fermentation broth without the need for energy‐intensive water separation. Increased concentration of MEK in the aqueous feed results in increased activity towards olefin production. However, water inhibits catalyst deactivation from coking. A mechanistic investigation revealed the impact of the reaction environment (inert or reducing atmosphere) on the reaction pathways. In an inert environment, the mechanism involves consecutive aldol condensation of MEK and 3‐pentanone intermediate. Under reducing conditions two reaction pathways compete with each other as MEK hydrogenation to butenes occurs concurrently with the aldol condensation/decomposition.
First Bis(σ)‐borane Complexes of Group 6 Transition Metals: Experimental and Theoretical Studies
Authors: Lenczyk Carsten , Roy Dipak Kumar , Ghosh Bijoy , Schwarzmann Johannes , Phukan Ashwini K. , Braunschweig Holger
Published: May 2019

A series of bis(σ)‐borane complexes of Group 6 transition metals were prepared by direct dihydroborane coordination to the metal center. Reaction of [M(CO)3(PCy3)2] and two dihydroboranes [DurBH2] and [(Me3Si)2NBH2] (Dur=2,3,5,6‐Me4C6H) yielded bis(σ)‐borane complexes fac‐[M(CO)3(PCy3){η2‐(H2BR)}] (R=Dur; 1: M=Cr, 2: M=W; R=N(SiMe3)2; 3: M=Cr, 4: M=W). In the case of molybdenum, we have isolated an arene complex (5) with [DurBH2] in which the Dur group acts as a η6‐bound ligand, and with [(Me3Si)2NBH2] a similar bis(σ)‐borane complex was isolated, cis,trans‐[Mo(CO)2(PCy3)2{η2‐(H2BN(SiMe3)2}] (6), with a different pattern of auxiliary ligands. The complexes were investigated by multinuclear NMR spectroscopy, mass spectrometry, X‐ray diffraction analysis, and computational methods. Quantum theory of atoms in molecules (QTAIM) calculations demonstrated that the borane complexes may be described as pure bis(σ)‐borane complexes rather than elongated or stretched examples given that the calculations do not show the presence of a ring‐critical point (RCP) at the ring formed by the interactions of the B−H with metal center.
Visible‐Light‐Promoted Ring‐Opening Alkynylation, Alkenylation, and Allylation of Cyclic Hemiacetals through β‐Scission of Alkoxy Radicals
Authors: Shi Jiang‐Ling , Wang Zixuan , Zhang Rui , Wang Yuankai , Wang Jianbo
Published: May 2019

The alkoxy radicals that are derived from cyclic hemiacetals have been generated through the visible‐light‐promoted reaction of the corresponding N‐alkoxyphthalimides with Hantzsch ester as the reductant. The alkoxy radicals subsequently undergo β‐scission of the C−C bond to generate carbon‐centered radicals, which are trapped by alkynyl‐, alkenyl‐, or allylsulfones.
Synthesis of Air‐stable, Odorless Thiophenol Surrogates via Ni‐Catalyzed C−S Cross‐Coupling
Authors: Magné Valentin , Ball Liam T.
Published: May 2019

Thiophenols are versatile synthetic intermediates whose practical appeal is marred by their air sensitivity, toxicity and extreme malodor. Herein we report an efficient catalytic method for the preparation of S‐aryl isothiouronium salts, and demonstrate that these air‐stable, odorless solids serve as user‐friendly sources of thiophenols in synthesis. Diverse isothiouronium salts featuring synthetically useful functionality are readily accessible by nickel‐catalyzed C−S cross‐coupling of (hetero)aryl iodides and thiourea. Convenient, chromatography‐free isolation of these salts is achieved by precipitation, allowing the methodology to be applied directly to large scales. Thiophenols are liberated from the corresponding isothiouronium salts upon treatment with a weak base, enabling an in situ release/S‐functionalization strategy that entirely negates the need to isolate, purify or manipulate these noxious reagents.
Catalytic Hydrogenation of Acetic Acid to Acetaldehyde: Synergistic Effect of Bifunctional Co/Ce‐Fe Oxide Solid Solution Catalysts
Authors: Li Naixu , Zhang Qi , Bibi Rehana , Shen Quanhao , Ngulube Richard , Liu Yunyi , Zhou Jiancheng
Published: May 2019

Summary of main observation and conclusion

The large‐scale industrial production of acetic acid (HAc) from carbonylation of methanol has enabled intense research interest from direct hydrogenation of HAc to acetaldehyde (AA). Herein, a series of cerium‐iron oxide solid solution supported metallic cobalt catalysts were prepared by modified sol‐gel method and were applied in gas‐phase hydrogenation of HAc to AA. A synergistic effect between the hydrogenation metal cobalt and Ce‐Fe oxide solid solution is revealed. Specifically, oxygen vacancies provide the active sites for adsorption of HAc, while highly uniformly dispersed metallic Co adsorbs H2 and activates the reduction of HAc into AA. Moreover, the metallic Co can also assist the cyclical conversion between Fe3+/Fe2+ and Ce3+/Ce4+ on the surface of Ce1‐xFexO2‐δ supports. The unique effect substantially enhances the ability of the support material to rapidly capture oxygen atoms from HAc. It is found that the catalyst of 5% Co/Ce0.8Fe0.2O2‐δ with the highest concentration of oxygen vacancy presents the best catalytic performance (i.e. acetaldehyde yield reaches 49.9%) under the optimal reaction conditions (i.e. 623 K and H2 flow rate = 10 mL/min). This work indicates that the Co/Ce‐Fe oxide solid solution catalyst can be potentially used for the selective hydrogenation from HAc to AA. The synergy between the metallic Co and Ce1‐xFexO2‐δ revealed can be extended to the design of other composite catalysts.
Structural States of Hdm2 and HdmX: X‐ray Elucidation of Adaptations and Binding Interactions for Different Chemical Compound Classes
Authors: Kallen Joerg , Izaac Aude , Chau Suzanne , Wirth Emmanuelle , Schoepfer Joseph , Mah Robert , Schlapbach Achim , Stutz Stefan , Vaupel Andrea , Guagnano Vito , Masuya Keiichi , Stachyra Therese‐Marie , Salem Bahaa , Chene Patrick , Gessier Francois , Holzer Philipp , Furet Pascal
Published: May 2019

Hdm2 (human MDM2, human double minute 2 homologue) counteracts p53 function by direct binding to p53 and by ubiquitin‐dependent p53 protein degradation. Activation of p53 by inhibitors of the p53–Hdm2 interaction is being pursued as a therapeutic strategy in p53 wild‐type cancers. In addition, HdmX (human MDMX, human MDM4) was also identified as an important therapeutic target to efficiently reactivate p53, and it is likely that dual inhibition of Hdm2 and HdmX is beneficial. Herein we report four new X‐ray structures for Hdm2 and five new X‐ray structures for HdmX complexes, involving different classes of synthetic compounds (including the worldwide highest resolutions for Hdm2 and HdmX, at 1.13 and 1.20 Å, respectively). We also reveal the key additive 18‐crown‐ether, which we discovered to enable HdmX crystallization and show its stabilization of various Lys residues. In addition, we report the previously unpublished details of X‐ray structure determinations for eight further Hdm2 complexes, including the clinical trial compounds NVP‐CGM097 and NVP‐HDM201. An analysis of all compound binding modes reveals new and deepened insight into the possible adaptations and structural states of Hdm2 (e.g., flip of F55, flip of Y67, reorientation of H96) and HdmX (e.g., flip of H55, dimer induction), enabling key binding interactions for different compound classes. To facilitate comparisons, we used the same numbering for Hdm2 (as in Q00987) and HdmX (as in O15151, but minus 1). Taken together, these structural insights should prove useful for the design and optimization of further selective and/or dual Hdm2/HdmX inhibitors.
An updated analysis of 4 randomized ECOG trials of high‐dose interferon in the adjuvant treatment of melanoma
Authors: Najjar Yana G. , Puligandla Maneka , Lee Sandra J. , Kirkwood John M.
Published: May 2019

Background

The pivotal E1684, E1690, E1694, and E2696 trials of adjuvant high‐dose interferon‐α (HDI) enrolled nearly 2000 patients, and established HDI as the standard of care in adjuvant therapy for patients with resected high‐risk melanoma. Herein, the authors present an updated analysis of these 4 trials.

Methods

Survival and disease status were updated in September 2016. These data represent a median follow‐up of 17.9 years for the E1684 trial, 12.2 years for the E1690 trial, 16.0 years for the E1694 trial, and 16.5 years for the E2696 trial.

Results

The current analysis confirmed the benefit to recurrence‐free survival (RFS) of HDI in the E1684 trial at a median follow‐up of 17.9 years. The RFS benefit in the E1694 trial remained evident at a median follow‐up of 16 years. Furthermore, the results of the current study confirmed the RFS benefit of adjuvant HDI compared with observation in a pooled analysis of the E1684 and E1690 trials. No overall survival benefit was apparent in this pooled analysis. Updated results for the E1690 and E2696 trials did not differ from those previously reported. In addition, to the authors’ knowledge, the current study is the first to report a significant difference in melanoma‐specific survival (MSS) between patients treated with HDI compared with the ganglioside GM2/keyhole limpet hemocyanin (GMK) vaccine in the E1694 trial.

Conclusions

In patients with resected high‐risk melanoma, adjuvant HDI demonstrated improved RFS in the E1684 and E1694 trials, and improved MSS in a pooled analysis of HDI in the E1694 trial. To the authors’ knowledge, these findings represent the most mature level of evidence for the benefit of HDI with respect to RFS and MSS. HDI is the only approved adjuvant treatment for which there are data available in patients with resected stage IIB/IIC melanoma, and remains a reasonable treatment option in this population.
Dependence of the Properties of 2D Nanocomposites Generated by Covalent Crosslinking of Nanosheets on the Interlayer Separation: A Combined Experimental and Theoretical Study
Authors: Singh Reetendra , Gupta Uttam , Kumar V. Sampath , Ayyub Mohd Monis , Waghmare Umesh V. , Rao C. N. R.
Published: May 2019

Covalently cross‐linked heterostructures of 2D materials are a new class of materials which possess electrochemical and photochemical hydrogen evolution properties. It was of considerable interest to investigate the role of interlayer spacing in the nanocomposites involving MoS2 and graphene sheets and its control over electronic structures and catalytic properties. We have investigated this problem with emphasis on the hydrogen evolution properties of these structures by a combined experimental and theoretical study. We have linked MoS2 based nanocomposites with other 2D materials with varying interlayer spacing by changing the linker and studied their hydrogen evolution properties. The hydrogen evolution activity for these composites decreases with increasing linker length, which we can link to a decrease in magnitude of charge transfer across the layers with increasing interlayer spacing. Factors such as the nature of the sheets, interlayer distance as well as the nature of the linker provide pathways to tune the properties of covalently cross‐linked 2D material rendering this new class of materials highly interesting.
Effect of Ligand Chirality and Hyperconjugation on the Thermodynamic Stability of a Tris(aquated) GdIII Complex: Synthesis, Characterization, and T1‐Weighted Phantom MR Image Study
Authors: Khannam Mahmuda , Sahoo Suban K. , Mukherjee Chandan
Published: May 2019

The hexadentate chiral alanine‐based ligand, Li3cbda, in a reaction with hydrated GdCl3 at pH ~ 6.5 provided the corresponding nine‐coordinated, neutral GdIII complex (1). The hydration state (q) of complex 1 was 3.1 ± 0.1, as determined by luminescence decay time measurements of TbIII congener in H2O and D2O. Complex 1 exhibited thermodynamic stability, log KGdL = 14.64 in 0.15 m NaCl solution at 25 °C. At 1.41 T, pH ≈ 7.4, and 25 °C, the complex offered longitudinal relaxivity, r1 = 10.95 mm–1 s–1, which was in accordance with three inner‐sphere water molecules. While, the relaxivity value remained unaffected in the pH range of 4.0 to 7.4, under basic conditions (pH ≥ 10) a reduction in the relaxivity value to 6.68 mm–1 s–1 was observed. A similar phenomenon was also realized in the presence of endogenous anions (100 equivalents of F– and HCO3–), which implied the removal of coordinated‐water molecules under the conditions. Phantom MR imaging under the clinical scanner at 1.5 T showed the enhancement in the image intensity with increasing concentration of the complex. As expected, the image intensity of 1 mm complex 1 was about three times compared to 1 mm MultiHance® solution.
Detection of the Elusive Nitrogen‐Centered Radicals from Catalytic Hofmann–Löffler Reactions
Authors: Bosnidou Alexandra E. , Duhamel Thomas , Muñiz Kilian
Published: May 2019

The catalytic Hofmann–Löffler reaction represents a uniquely effective protocol for the formation of pharmaceutically relevant heterocycles and is based on the reactivity of N‐halogenated amines. Herein, we report stoichiometric experimentation toward the detection of a sulfonamidyl radical as the decisive intermediate in this C‐H amination reaction. It can be observed by EPR after homolytic cleavage of the in situ formed N‐halogen bond under the conditions of the iodine or bromine catalyzed Hofmann–Löffler reaction.
Structure‐Based Design, Synthesis and Biological Evaluation of Bis‐Tetrahydropyran Furan Acetogenin Mimics Targeting the Trypanosomatid F1 Component of ATP Synthase
Authors: Zacharova Marija K. , Tulloch Lindsay B. , Gould Eoin R. , Fraser Andrew L. , King Elizabeth F. , Menzies Stefanie K. , Smith Terry K. , Florence Gordon J.
Published: May 2019

The protozoan parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for the severely debilitating neglected Tropical diseases of African sleeping sickness, Chagas disease and leishmaniasis, respectively. As part of our ongoing programme exploring the potential of simplified analogues of the acetogenin chamuvarinin we identified the T. brucei FoF1‐ATP synthase as a target of our earlier triazole analogue series. Using computational docking studies, we hypothesised that the central triazole heterocyclic spacer could be substituted for a central 2,5‐substituted furan moiety, thus diversifying the chemical framework for the generation of compounds with greater potency and/or selectivity. Here we report the design, docking, synthesis and biological evaluation of new series of trypanocidal compounds and demonstrate their on‐target inhibitory effects. Furthermore, the synthesis of furans by the modular coupling of alkyne‐ and aldehyde‐THPs to bis‐THP 1,4‐alkyne diols followed by ruthenium/xantphos‐catalysed heterocyclisation described here represents the most complex use of this method of heterocyclisation to date.
Treatments and uses of Moringa oleifera seeds in human nutrition: A review
Authors: Saa Romuald Willy , Fombang Edith Nig , Ndjantou Elie Baudelaire , Njintang Nicolas Yanou
Published: May 2019

This work reviews treatments and uses of Moringa oleifera seeds in human nutrition. Moringa oleifera seeds are considerable sources of proteins (mean 19%) and lipids (mean 31%). Previous reports presented the nutritional properties of the seeds and oil. Moringa seeds are sources of lipids, and their removal leads to Moringa seed flour with a high protein content which might play a role in food technology and human nutrition. Moringa oil has been tested in frying and was found to be more stable than groundnut oil; its incorporation in groundnut at level lower than 10% improved on the acceptability of chips. Several treatments like roasting, germination, and boiling have been applied to Moringa seeds to produce flour with improved nutritional properties. In particular, defatted Moringa flour has been applied in different formulations including cakes, cookies, burgers, infant porridges. Generally, the products deriving from the flour were more stable in conservation and well accepted for low substitution while high substitution increased the bitterness. Notwithstanding their high content in protein and oil, defatted M. oleifera seed flour and oil are still fairly investigated in order to envisage their integration in the food habits of people. The present wrote up reviews the treatments applied on M. oleifera seeds and applications of the defatted M. oleifera flour and oil in food systems for human nutrition.
Introduction of a novel guided bone regeneration memory shape based device
Authors: Zakaria Osama , Madi Marwa , Kasugai Shohei
Published: May 2019

Bone regeneration by periosteal distraction has been reported in numerous animal studies; however, the main disadvantages of this technique are poor bone quality and soft tissue invasion in the distracted space. The purpose of this study was to evaluate a novel shape memory‐based device to promote bone regeneration in a large, secluded growth space in a rabbit model. Twenty rabbits were divided into two groups. In the first group (n = 10), a device composed of silicone sheets and nitinol strips was inserted subperiosteally in the calvarial area. In the second group (n = 10), only silicone sheets were inserted in the calvarial area. Each group was further divided in half: five animals were sacrificed at 8 weeks postoperatively, and the other five were sacrificed at 16 weeks postoperatively. In the study group, the new device vertically expanded the overlying soft tissue 4 mm above the original bone and created a secluded space; the newly generated bone maximum height median ranged between 2.7 mm in 8 weeks group and 2.6 mm in 16 weeks group. In the control group, a very thin rim of bone was generated below the flat silicone sheets on top of the original bone. Maximum bone heights median ranged from 0.37 mm in 8 weeks group to 0.32 mm in 16 weeks group. The device was proven to be effective at vertically augmenting bone by applying the guided bone regeneration and soft tissue expansion procedures simultaneously. This device may pave the way for a new generation of smart guided bone regeneration membranes that can remember the original dimensions of resorbed bone areas.
Mechanistic investigations of the liver toxicity of the free fatty acid receptor 1 agonist fasiglifam (TAK875) and its primary metabolites
Authors: Ackerson Timothy , Amberg Alexander , Atzrodt Jens , Arabeyre Catherine , Defossa Elisabeth , Dorau Martina , Dudda Angela , Dwyer Jacquelyn , Holla Wolfgang , Kissner Thomas , Kohlmann Markus , Kürzel Ulrich , Pánczél József , Rajanna Shibani , Riedel Jens , Schmidt Friedemann , Wäse Kerstin , Weitz Dietmar , Derdau Volker
Published: May 2019

For fasiglifam (TAK875) and its metabolites the substance‐specific mechanisms of liver toxicity were studied. Metabolism studies were run to identify a putatively reactive acyl glucuronide metabolite. In vitro cytotoxicity and caspase 3/7 activation were assessed in primary human and dog hepatocytes in 2D and 3D cell culture. Involvement of glutathione (GSH) detoxication system in mediating cytotoxicity was determined by assessing potentiation of cytotoxicity in a GSH depleted in vitro system. In addition, potential mitochondrial liabilities of the compounds were assessed in a whole‐cell mitochondrial functional assay. Fasiglifam showed moderate cytotoxicity in human primary hepatocytes in the classical 2D cytotoxicity assays and also in the complex 3D human liver microtissue (hLiMT) after short‐term treatment (24 hours or 48 hours) with TC50 values of 56 to 68 µM (adenosine triphosphate endpoint). The long‐term treatment for 14 days in the hLiMT resulted in a slight TC50 shift over time of 2.7/3.6 fold lower vs 24‐hour treatment indicating possibly a higher risk for cytotoxicity during long‐term treatment. Cellular GSH depletion and impairment of mitochondrial function by TAK875 and its metabolites evaluated by Seahorse assay could not be found being involved in DILI reported for TAK875. The acyl glucuronide metabolites of TAK875 have been finally identified to be the dominant reason for liver toxicity.
Retracted: Long noncoding RNA MT1JP inhibits proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway
Authors: Zhang Ye , Sui Rui , Chen Yi , Liang Hanyang , Shi Ji , Piao Haozhe
Published: May 2019

This study is carried out to elucidate the role of long noncoding RNAs (lncRNAs) MT1JP in proliferation, invasion, migration, and apoptosis of glioma cells through the regulation of PTEN/Akt signaling pathway. The expression of MT1JP in 80 normal brain tissues and 138 glioma tissues, as well as glioma cell lines, was detected by quantitative reverse‐transcription polymerase chain reaction. Besides, glioma cells with overexpression and low expression of MT1JP were constructed to confirm the role of MT1JP in proliferation, invasion, migration, and apoptosis of glioma cells and the growth of glioma cells in vivo through the regulation of PTEN/Akt signaling pathway. MT1JP expression was downregulated in glioma tissues and cells. The low expression of MT1JP was considered as an independent risk factor for predicting overall survival in gliomas. After transfection of MT1JP overexpression plasmid, glioma cells showed decreased proliferation, migration and invasion ability, increased apoptosis rate, and decreased the tumorigenic ability of nude mice. The trends were opposite in glioma cells transfected with MT1JP poor expression plasmid. Collectively, our study suggests that lncRNA MT1JP is responsible for inhibiting proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway.
miR‐324‐5p protects against oxidative stress‐induced endothelial progenitor cell injury by targeting Mtfr1
Authors: Chen Peier , Zhong Jianfeng , Ye Jianfeng , He Yuan , Liang Zheng , Cheng Yu , Zheng Jie , Chen Hao , Chen Can
Published: May 2019

Endothelial progenitor cells (EPCs) belong to bone marrow‐derived myeloid progenitor cells that have strong proliferative ability. Dysregulation of miRNAs after acute myocardial infarction (AMI) can result in EPCs injury, thus we hypothesize that correction of miRNA expression may contribute to the tolerance of EPCs against oxidative stress. The peripheral blood of healthy volunteers and patients with ST‐segment elevation myocardial infarction (STEMI) was clinically collected. EPCs derived from peripheral blood were transfected by miR‐324‐5p mimic and simultaneously handled with hydrogen peroxide (H2O2) to inducing EPCs injury. At 24 hrs after the H2O2 treatment, cell viability, the uptake capacity on DiI‐Ac‐LDL, and carrying ability on FITC‐UEA‐l and multiplication capacity were analyzed. The mechanism process was carefully researched by valued the characteristics of the mitochondrion morphology, membrane potential, ATP levels, and the expressing of apoptosis pathways. Small RNA sequencing indicated that the expression level of miR‐324‐5p in peripheral blood EPCs of patients with STEMI was significantly lower compared with the healthy volunteers. The Mtfr1 has been confirmed as a targeted gene of miR‐324‐5p through miRTarBase software and western blot. The miR‐324‐5p mimic units could be contributed for the improvement of viability, the uptake capacity on DiI‐Ac‐LDL and carrying ability on FITC‐UEA‐l and multiplication capacity on oxidative stress‐injured EPCs. miR‐324‐5p could suppress mitochondrial fragmentation, promote membrane potential, and ATP levels, as well as protect against oxidative stress‐induced EPCs apoptosis. Our results suggested that miR‐324‐5p protects against oxidative stress‐induced EPCs injury by regulating Mtfr1.
Ni‐induced TGF‐β signaling promotes VEGF‐a secretion via integrin β3 upregulation
Authors: Wu Chih‐Hsien , Ko Jiunn‐Liang , Pan Hui‐Hsien , Chiu Ling‐Yen , Kang Yu‐Ting , Hsiao Yu‐Ping
Published: May 2019

Nickel compounds are associated with lung and skin cancer incidence increase and accumulation of nickel in the body contributes to carcinogenesis. Upregulation of certain integrins in the primary tumor is associated with cancer metastasis and poor prognosis. However, the molecular mechanisms of nickel‐induced cancer metastasis are still unclear. The purpose of the present study was to investigate the effects of nickel chloride (NiCl2) on the progression of cancer during metastasis. The results of showed that NiCl2 induces the expression of integrin β3 mRNA and protein in a dose‐ and time‐dependent manner. Inhibition of integrin αvβ3 activation by ITGB3 ligand mimetics and GR144053, as well as downregulation of ITGB3 by lentiviral shRNA gene silencing, diminished NiCl2‐induced secretion of vascular endothelial growth factor‐a (VEGF‐a). Furthermore, pretreatment with type I TGF‐β receptor inhibitor, SB525334, suppressed the expression of ITGB3 at cell surface and secretion of VEGF‐a in NiCl2‐treated cells. In conclusion, NiCl2 induces the expression of ITGB3 through TGF‐β signaling activation, followed by increasing VEGF‐a secretion, revealing a novel role for ITGB3 in nickel compound‐induced cancer metastasis and tumor angiogenesis.
The dermal skeleton of the jawless vertebrateTremataspis mammillata(Osteostraci, stem‐Gnathostomata)
Authors: O'Shea James , Keating Joseph N. , Donoghue Philip C. J.
Published: May 2019

Osteostracans are the closest jawless relatives of jawed vertebrates, informing the gradual assembly of the vertebrate mineralised skeleton. Conflicting interpretations of their dermal skeletal histology arise from failure to account for topological variation, obscuring their significance in elucidating vertebrate skeletal evolution. To resolve this, we characterize the cranial and trunk dermal skeleton of a single individual ofTremataspis mammillata(Osteostraci, Thyestiida) at submicron resolution using synchrotron‐ and computed‐ tomography. Our results show that the architecture of theTremataspisdermal skeleton is, for the most part, conserved over the skeleton and is broadly consistent with previous histological hypotheses based on 2D thin section study. We resolve debate over the homology of the basal layer, identifying it as osteogenic acellular isopedin rather than odontogenic elasmodine or metaplastic ossification of the stratum compactum of the dermis. We find topological variation between all dermal skeletal elements studied, and particularly between the cranial and postcranial dermal skeleton. This variation can be largely explained by reduction in differentiation due to geometric constraints imposed within smaller skeletal elements, such as scales. Our description of the dermal skeleton ofTremataspis mammillataprovides a foundation for interpreting data from cursory topological samples of dermal skeletal diversity obtained in other osteostracans. This reveals general aspects of histological structure that must be ancestral for osteostracans and, likely, ancestral jawed vertebrates. Finally, we draw the distinction between hypotheses and descriptions in palaeohistology.
Rapid detection and clinical spectrum of the novel influenza H1N1 strain in a diabetic pediatric population
Authors: Ammar Rania A. , Montasser Karim , Ezz Hoda , Albishi Laila A. , Ghareeb Ahmed
Published: May 2019

Objectives

H1N1 infection in diabetic patients is of special concern and serious interest since the virus can place individuals, especially children, at great possible risk of subsequently developing type 1 diabetes. This work aims to describe the demographic characteristics, clinical features, and severity of illness of children with type 1 diabetes mellitus (DM), compare the incidence of pandemic H1N1 virus in children with that of the general pediatric population with influenza‐like symptoms, and identify the complications of H1N1 virus infection associated with glycemic control.

Methods

The present study included 45 children and adolescents with type 1 diabetes, who were subject to clinical and laboratory investigations. Another 30 healthy adolescents and children with a mean age of 10.43 ± 4.38 years were included as a control group. H1N1 reverse‐transcriptase quantitative PCR (RT‐Q PCR) was tested for H1N1 virus detection.

Results

Diabetic patients positive for (H1N1) showed significantly higher random blood sugar (RBS) levels than diabetic patients negative for (H1N1). Moreover, the H1N1‐positive patients had significantly higher hemoglobin (Hb) g/dL, platelet counts, total leukocyte counts (TLCs), and CRP levels. Newly diagnosed patients who were tested positive for (H1N1) and diabetic ketoacidosis (DKA) had significantly higher RBS levels and TLCs than patients who were presented with hyperglycemia.

Conclusion

RT‐PCR is a rapid and specific method for influenza A (H1N1) virus diagnosis. In addition, early administration of oseltamivir no later than 48 hours after the infection is highly recommended in either diabetic or DKA patients suspected of having H1N1.
Transvaginal Real‐time Shear Wave Elastography in the Diagnosis of Cervical Disease
Authors: Liu Chun , Li Ting Ting , Hu Ziyue , Li Yuan , Cheng Xueqing , Zhu Yi , Lu Man
Published: May 2019

Objectives

To explore the value of shear wave elastography in the diagnosis of cervical disease.

Methods

This work was a retrospective analysis of 246 cases of cervical lesions confirmed by transvaginal conventional ultrasound, shear wave elastography, and a cytologic test. The lesions were divided into 2 groups according to the final pathologic results: a malignant cervical group and a benign cervical group. In addition, the normal cervix was set as the control group.

Results

The maximum and mean shear wave velocity values ± SD were 5.24 ± 1.11 and 4.91 ± 1.12 m/s for the malignant cervical group, 3.93 ± 0.39 and 3.53 ± 0.52 m/s for the benign cervical group, and 3.27 ± 0.31 and 2.86 ± 0.23 m/s for the normal cervix, respectively. The areas under the receiver operating characteristic curves for the maximum and mean shear wave velocity in the differential diagnosis of a normal cervix and benign cervical tumors were 0.909 and 0.878 (both P < .001), whereas in the differential diagnosis of benign and malignant cervical tumors, they were 0.909 and 0.895 (both P < .001).

Conclusions

Shear wave elastography can quantitatively analyze the elastic characteristics of cervical diseases, help differentially diagnose cervical diseases, accurately determine the extent of tumor invasion, and improve effective clinical staging and treatment.
Susane, a device for sampling chemical gradients in the benthic water column
Authors: Knoery Joël , Cossa Daniel , Thomas Bastien , Gregory Germain , Rigaud Sylvain
Published: May 2019

In aquatic environments, the benthic water column exhibits strong concentration gradients of various substances. They result from transfers and chemical reactions that may occur both within this layer, and at the sediment–water interface (SWI). Characterization of these gradients yields important information for the quantification of such processes and transfers. However, it is difficult to actually sample these gradients in the field, since turbulence decreases their vertical scale. This article describes a sampler designed to collect simultaneously 16 discrete water column samples at a centimeter‐scale vertical resolution. This small device (40 × 40 × 60 cm) is reliable, safe to handle, and easily deployed from a small boat using a cable or a Scuba diver. It is made of materials compatible with trace element and dissolved gases work, and simultaneously draws samples from various heights above the SWI into 60 mL syringes. The altitude of the sample inlets is field‐adjustable. Sampling artifacts are minimized by in situ flushing of tubing dead volumes, by rapid and simultaneous sample collection, and by sampling an undisturbed water‐column. Thus, this device can contribute to the characterization of vertical concentration gradients in benthic water‐columns. Such gradients of various compounds and metals from two coastal sites (Quiberon Bay and Berre Lagoon) are shown, illustrating the sampler's usefulness to describe and investigate processes in the benthic zone.
Mass Spectrometric Lipid Profiles of Picosecond Infrared Laser‐Generated Tissue Aerosols Discriminate Different Brain Tissues
Authors: Wurlitzer Marcus , Hessling Elisabeth , Rinas Karsten , Fuh MarcelineManka , Petersen Hannes , Ricklefs Franz , Lamszus Katrin , Regelsberger Jan , Maier Stephanie , Kruber Sebastian , Hansen Nils‐Owe , Miller RJDwayne , Schlüter Hartmut
Published: May 2019

Background and Objectives

A picosecond infrared laser (PIRL) has recently been demonstrated to cut biological tissue without scar formation based on the minimal destructive action on the surrounding cells. During cutting with PIRL, the irradiated tissue is ablated by a cold vaporization process termed desorption by impulsive vibrational excitation. In the resulting aerosol, all molecules are dissolved in small droplets and even labile biomolecules like proteins remain intact after ablation. It is hypothesized that these properties enable the PIRL in combination with mass spectrometry as an intelligent laser scalpel for guided surgery. In this study, it was tested if PIRL‐generated tissue aerosols are applicable for direct analysis with mass spectrometry, and if the acquired mass spectra can be used to discriminate different brain areas.

Materials and Methods

Brain tissues were irradiated with PIRL. The aerosols were collected and directly infused into a mass spectrometer via electrospray ionization without any sample preparation or lipid extraction.

Results

The laser produced clear cuts with no marks of burning. Lipids from five different classes were identified in the mass spectra of all samples. By principal component analysis the different brain areas were clearly distinguishable from each other.

Conclusions

The results demonstrate the potential for real‐time analysis of lipids with a PIRL‐based laser scalpel, coupled to a mass spectrometer, for the discrimination of tissues during surgeries. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Acute Rat and Mouse Oral Toxicity Determination of Anticholinesterase Inhibitor Carbamate Pesticides: A QSTR Approach
Authors: Roy Partha Pratim , Banjare Purusottam , Verma Sandhya , Singh Jagadish
Published: May 2019

The toxic potentials of carbamates to human and non target organisms are of public concern in relation to society and ecosystem for their unregulated and indiscriminate use. No computational study was found on rat and mouse oral toxicity for carbamate pesticides. In this context, carbamate pesticides were collected from ChemIDplus databases for the modeling study. A series of local QSTR model for both rat and mouse oral toxicity of carbamate derivatives were developed according to OECD principle from 2D descriptors by using Genetic Algorithm (GA) as feature selection chemometric tools using QSARINS software. All the models indicate the importance of auto correlation descriptors related to charge, I‐State, atom type E state for fragment −O− in relation to acute mammalian toxicity. Reliability of predictions of the models was verified by applicability domain (AD) and prediction reliability index. Finally developed models were applied to unknown carbamate pesticides to evaluate their predictions and AD. The toxic nature of the prioritized compounds with structural alerts were commented in a consensus way. Additional toxicity‐toxicity relationship studies (QTTR) between these two responses with similar findings promoted further application of QTTR models in absence of one response. These findings may help the scientific community in prioritizing potentially hazardous pesticides of carbamate and related classes.
Resveratrol improved the developmental potential of oocytes after vitrification by modifying the epigenetics
Authors: Chen Huanhuan , Zhang Lei , Wang Zhenqiang , Chang Haoya , Xie Xiaogang , Fu Liangzheng , Zhang Yong , Quan Fusheng
Published: May 2019

Resveratrol (Res) has been reported to be able to improve oocyte vitrification because of its antioxidative properties. The objective of this study was to further assess the positive effect of Res addition on the developmental potential of vitrified mouse oocytes from the perspective of epigenetic alterations. First, 2 μM Res was chosen as the optimal concentration on the basis of its effects on survival and its antioxidative properties. We found that Res addition significantly promoted fertilization (63.8% vs. 42.9%) and blastocyst formation (68.3% vs. 50.2%) after oocyte vitrification. The quality of the derived blastocysts was also higher after Res treatment. Regarding epigenetic aspects, the expression of the important deacetylase SIRT1 was found to decrease significantly upon vitrification, but it was rescued by Res. The abnormal levels of H3K9 acetylation and DNA methylation in vitrified oocytes were restored by Res addition. Moreover, the expression of several imprinted genes was affected by oocyte vitrification. Among them, abnormal Gtl2 and Peg3 expression levels were restored by Res addition. Therefore, the methylation of their imprinted control regions (ICRs) was examined. Surprisingly, the abnormal patterns of Gtl2 and Peg3 methylation in blastocysts developed from vitrified oocytes were both restored by Res addition. Finally, the full‐term embryonic development showed that the birth rate was improved significantly by Res addition (56.2% vs. 38.1%). Collectively, Res was beneficial for the pre‐ and postimplantation embryonic development. Except for the antioxidative activity, Res also played a role in the correction of some abnormal epigenetic modifications caused by oocyte vitrification.
Changes in calcium levels in the endometrium throughout pregnancy and the role of calcium on endometrial gene expression at the time of conceptus implantation in pigs
Authors: Choi Yohan , Jang Hwanhee , Seo Heewon , Yoo Inkyu , Han Jisoo , Kim Minjeong , Lee Soohyung , Ka Hakhyun
Published: May 2019

Calcium plays an essential role in regulating many cellular functions, including proliferation, differentiation, and apoptosis. In spite of its importance in the establishment and maintenance of pregnancy, changes in calcium levels at the maternal–conceptus interface during pregnancy and its action on endometrial gene expression are not well understood. Thus, we examined changes in calcium levels in the endometrium during pregnancy, calcium deposition at the maternal–conceptus interface during pregnancy, and the role of calcium on the expression of endometrial genes related to conceptus implantation during early pregnancy in pigs. The amounts of endometrial calcium increased during mid‐ to late pregnancy, and calcium deposition was mainly localized to endometrial and chorionic epithelial cells at the maternal–conceptus interface during pregnancy and conceptus tissues during early pregnancy. The amounts of total recoverable calcium in uterine flushings were greater on Day 12 of pregnancy than Day 12 of the estrous cycle, and estrogen increased absorption of calcium ions by endometrial tissues. Increasing endometrial calcium levels by treatment with A23187, a calcium ionophore, decreased the expression of the estrogen‐responsive endometrial genes AKR1B1, ESR1, FGF7, IL1RAP, LPAR3, S100G, SPP1, and STC1 and increased the expression of genes related to prostaglandin synthesis and transport, namely PTGES, PTGS2, and SLCO5A1. These data suggest that calcium ions at the maternal–conceptus interface play a critical role in the establishment and maintenance of pregnancy in pigs by regulating the expression of endometrial genes involved in conceptus implantation, as well as the attachment of endometrial epithelial and conceptus trophectoderm/chorionic epithelial cells during pregnancy.
A branch‐and‐price algorithm for the vehicle routing problem with time windows on a road network
Authors: Ben Ticha Hamza , Absi Nabil , Feillet Dominique , Quilliot Alain , Van Woensel Tom
Published: May 2019

Vehicle routing problems (VRP) concern the pickup and/or the delivery of goods from/to customers with vehicles. In the literature, most approaches consider the road network implicitly. Specifically, so‐called customer‐based graphs are used where nodes represent customers (plus the depot) and arcs represent best paths between customers. This model can affect solution quality when several attributes are defined on road segments (like travel time and distance). To handle that, two approaches are proposed in the literature. The road network can be represented using a multigraph that extends the customer‐based graph and where an arc is introduced for every efficient path between two nodes. Alternatively, the problem can be solved on a graph that mimics the original road network. In this paper, we investigate the latter approach. We consider the VRP with time windows (VRPTW) and we develop a branch‐and‐price scheme. An extensive computational study based on several types of instances is conducted in order to evaluate this approach compared to the multigraph‐based approach. As far as we know, our branch‐and‐price scheme is the first exact method for the VRPTW with the road‐network model. Also, our computational study provides the first comparison between the two models: multigraph and road‐network.