bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and biological evaluation of novel benzo[c]acridine‐diones as potential anticancer agents and tubulin polymerization inhibitors
Authors: Behbahani Fatemeh Shaebani , Tabeshpour Jamshid , Mirzaei Salimeh , Golmakaniyoon Sima , Tayarani‐Najaran Zahra , Ghasemi Ali , Ghodsi Razieh 
Published: April 2019

AbstractA new series of novel benzo[c]acridine‐diones possessing pharmacophoric elements of antitubulins with central dihydropyridine bridge were designed and synthesized as potential anticancer agents and tubulin polymerization inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against eight cancer cell lines including MCF‐7, A2780, HeLa, HepG2, DU145, A549, PC3, and LNCAP cancer cells and normal cells human umbilical vein endothelial cell (HUVEC) through 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide (MTT) assay, wherein β‐lapachone and combretastatin A‐4 were used as positive controls. Some of our compounds (4c and 4g) showed significant cytotoxic activity on cancer cells with IC50 values in the range of 5.23–24.32 μM. None of the synthesized compounds showed significant cytotoxicity on normal HUVEC cells. Among all investigated derivatives, compound 4g showed promising greater antiproliferative activity against all tested cancer cells with the highest sensitivity observed for the PC3 cell line. Results from the flow cytometry analysis of PC3 and MCF‐7 cancer cells treated with 4g showed an induced cell‐cycle arrest at G2/M, and therefore induced apoptosis which occurred at low concentration of test compound, whereas annexin V‐FITC/propidium iodide staining assay in the aforementioned cancer cell lines treated with 4g showed that 4g can cause necrosis in PC3 and MCF‐7 cancer cells at higher concentration. Compound 4g proved to be an inhibitor of tubulin polymerization in a mode similar to that of colchicine and in a dose‐dependent manner. Molecular docking studies of 4g into the colchicine‐binding site of tubulin exhibited a possible mode of interaction between this compound and tubulin.
Two‐Dimensional Metal‐Organic Layers for Electrochemical Acceptorless Dehydrogenation of N‐Heterocycles
Authors: Yang Ling , Ma Fa‐Xue , Xu Fan , Li Dong , Su Liangmei , Xu Hai‐Chao , Wang Cheng 
Published: April 2019

AbstractThe catalytic acceptorless dehydrogenation (CAD) is an attractive synthetic route to unsaturated compounds because of its high atomic efficiency. Here we report electrochemical acceptorless dehydrogenation of N‐heterocycles to obtain quinoline or indole derivatives using metal‐organic layer (MOL) catalyst. MOL is the two‐dimensional version of metal‐organic frameworks (MOF), and it can be constructed on conductive multi‐walled carbon nanotubes via facile solvothermal synthesis to overcome the conductivity constraint for MOFs in electrocatalysis. TEMPO‐OPO32− was incorporated into the system through a ligand exchange with capping formate on the MOL surface to serve as the active catalytic centers. The hybrid catalyst is efficient in the organic conversion and can be readily recycled and reused.
Processes of intraseasonal snow cover variations over the eastern China during boreal winter
Authors: Song Lei , Wu Renguang , Zhu Jialei 
Published: April 2019

AbstractThis study reveals that the dominant time scale of intraseasonal snow cover variation over the eastern China is within 30 days by using the latest satellite snow cover data from the moderate resolution imaging spectroradiometer (MODIS)/Terra product. The leading empirical orthogonal function (EOF) mode of 10–30‐day snow cover variation during boreal winter from 2004 to 2018 over the eastern China has two centers: northwest part of the eastern China and north of the Yangtze River. Composite analysis based on 25 snow events identified from normalized leading principal time series (PC1) indicates that the southeastward intrusion of surface anticyclonic anomalies and accompanying low temperature anomalies provide the temperature condition for snow events. Negative Arctic Oscillation induces mid‐latitude wave train and leads to the development of surface anticyclonic anomalies and upper‐level cyclonic anomalies over East Asia. The cyclonic anomalies induce ascending motion and anomalous convergence of water vapor fluxes over the eastern China, which supplies moisture for snowfall.
Synthesis of the N‐methyl Derivatives of 2‐Aminothiazol‐4(5H)‐one and Their Interactions with 11βHSD1‐Molecular Modeling and in Vitro Studies
Authors: Studzińska Renata , Kołodziejska Renata , Płaziński Wojciech , Kupczyk Daria , Kosmalski Tomasz , Jasieniecka Katarzyna , Modzelewska‐Banachiewicz Bożena 
Published: April 2019

Abstract11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is an enzyme that affects the body's cortisol levels. The inhibition of its activity can be used in the treatment of Cushing's syndrome, metabolic syndrome and type 2 diabetes. In this study, we synthesized new derivatives of 2‐(methylamino)thiazol‐4(5H)‐one and tested their activity towards inhibition of 11β‐HSD1 and its isoform – 11β‐HSD2. The results were compared with the previously tested allyl derivatives. We found out that methyl derivatives are weaker inhibitors of 11β‐HSD1 in comparison to their allyl analogs. Due to significant differences in the activity of the compounds, molecular modeling was performed, which was aimed at comparing the interactions between 11β‐HSD1 and ligands differing by substituent at the amine group (allyl vs. methyl). Modeling showed that the absence of the allyl group can lead to the rotation of whole ligand molecule which affects its interaction with the enzyme.
Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update
Authors: Meninno Sara , Volpe Chiara , Lattanzi Alessandra 
Published: April 2019

AbstractDiscovered more than one decade ago, α,α‐diaryl prolinols, most of them commercially available compounds, demonstrated to be distinctive organocatalysts in asymmetric synthesis. Their application successfully spanned across different carbon‐carbon or carbon‐heteroatom bond forming reactions and cascade processes, exploiting covalent and noncovalent activation of the reagents. In this minireview, the advances from 2013 up to the end of 2018 in α,α‐diaryl prolinols promoted stereoselective catalysis and synthesis of biologically active compounds, are illustrated.
Four‐dimensional quantitative structure‐activity analysis of 1,4‐naphthoquinone derivatives tested against HL‐60 human promyelocytic leukemia cells
Authors: Costa Maria Cristina A. , Carvalho Pedro O. Mariz , Ferreira Márcia M. C. 
Published: April 2019

AbstractFour‐dimensional quantitative structure‐activity relationship (4D‐QSAR) models were developed to predict biological activity of 1,4‐naphthoquinones derivatives tested against human HL‐60 leukemic cells, in order to better investigate the action mode of these compounds. Quinones can generate reactive oxygen species (ROS) through the activation by the cytochrome P450 and P450 reductase enzymes acting as anticancer agents. Molecular dynamics (MD) simulations were performed in the 3D optimized geometries, and the field descriptors were calculated. Partial least squares (PLS) regression method was applied to build the QSAR model, which presented the following statistics, with two factors and explaining 51.11% of total variance: R2 = 0.83; SEC = 0.28; Q2 = 0.77; SEV = 0.31. For external validation, the results were R2pred = 0.76 and SEP = 0.30. Among the nine Coulomb (C) and Lennard‐Jones (LJ) descriptors selected by the model, one of them, C13838, is located close to quinone oxygens involved in the production of radical anions (O2−·) and to hydroxyl in position 5 that may stabilize catalytically important water molecules. The negative LJ descriptors around R1 and R2 substituents might indicate that apolar substituents in these regions are unfavorable to the activity. Coulomb descriptors located at the vicinities of the substituent R2 gave information about the bioactive conformation.
Substitution of an Internal Disulfide Bridge with a Diselenide Enhances both Foldability and Stability of Human Insulin
Authors: Weil‐Ktorza Orit , Rege Nischay , Lansky Shifra , Shalev Deborah E. , Shoham Gil , Weiss Michael A. , Metanis Norman 
Published: April 2019

AbstractInsulin analogues, mainstays in the modern treatment of diabetes mellitus, exemplify the utility of protein engineering in molecular pharmacology. Whereas chemical syntheses of the individual A and B chains were accomplished in the early 1960s, their combination to form native insulin remains inefficient because of competing disulfide pairing and aggregation. To overcome these limitations, we envisioned an alternative approach: pairwise substitution of cysteine residues with selenocysteine (Sec, U). To this end, CysA6 and CysA11 (which form the internal intrachain A6–A11 disulfide bridge) were each replaced with Sec. The A chain[C6U, C11U] variant was prepared by solid‐phase peptide synthesis; while sulfitolysis of biosynthetic human insulin provided wild‐type B chain‐di‐S‐sulfonate. The presence of selenium atoms at these sites markedly enhanced the rate and fidelity of chain combination, thus solving a long‐standing challenge in chemical insulin synthesis. The affinity of the Se‐insulin analogue for the lectin‐purified insulin receptor was indistinguishable from that of WT‐insulin. Remarkably, the thermodynamic stability of the analogue at 25 °C, as inferred from guanidine denaturation studies, was augmented (ΔΔGu ≈0.8 kcal mol−1). In accordance with such enhanced stability, reductive unfolding of the Se‐insulin analogue and resistance to enzymatic cleavage by Glu‐C protease occurred four times more slowly than that of WT‐insulin. 2D‐NMR and X‐ray crystallographic studies demonstrated a native‐like three‐dimensional structure in which the diselenide bridge was accommodated in the hydrophobic core without steric clash.
Efficient Syntheses of Traumatic Lactone and Rhizobialide
Authors: Zhou Jing , Song Shihua , Jiang Feng , Fu Chunling , Ma Shengming 
Published: April 2019

AbstractHerein, we report the total synthesis of traumatic lactone and rhizobialide by utilizing allenoic acid to construct the lactone ring. The key starting materials, allenoic acids, could be prepared by the ATA (allenation of terminal alkynes) of a terminal alkyne with an aldehyde that contained a protected hydroxyl group followed by hydrolysis. Importantly, the asymmetric synthesis could be realized just by replacing racemic diphenylprinol with (R)‐ or (S)‐diphenylprinol to deliver the optically active allenoate.
Activating p53 family member TAp63: A novel therapeutic strategy for targeting p53‐altered tumors
Authors: Gunaratne Preethi H. , Pan Yinghong , Rao Abhi K. , Lin Chunru , Hernandez‐Herrera Anadulce , Liang Ke , Rait Antonina S. , Venkatanarayan Avinashnarayan , Benham Ashley L. , Rubab Farwah , Kim Sang Soo , Rajapakshe Kimal , Chan Clara K. , Mangala Lingegowda S. , Lopez‐Berestein Gabriel , Sood Anil K. , Rowat Amy C. , Coarfa Cristian , Pirollo Kathleen F. , Flores Elsa R. , Chang Esther H. 
Published: April 2019

BackgroundOver 96% of high‐grade ovarian carcinomas and 50% of all cancers are characterized by alterations in the p53 gene. Therapeutic strategies to restore and/or reactivate the p53 pathway have been challenging. By contrast, p63, which shares many of the downstream targets and functions of p53, is rarely mutated in cancer.MethodsA novel strategy is presented for circumventing alterations in p53 by inducing the tumor‐suppressor isoform TAp63 (transactivation domain of tumor protein p63) through its direct downstream target, microRNA‐130b (miR‐130b), which is epigenetically silenced and/or downregulated in chemoresistant ovarian cancer.ResultsTreatment with miR‐130b resulted in: 1) decreased migration/invasion in HEYA8 cells (p53 wild‐type) and disruption of multicellular spheroids in OVCAR8 cells (p53‐mutant) in vitro, 2) sensitization of HEYA8 and OVCAR8 cells to cisplatin (CDDP) in vitro and in vivo, and 3) transcriptional activation of TAp63 and the B‐cell lymphoma (Bcl)‐inhibitor B‐cell lymphoma 2‐like protein 11 (BIM). Overexpression of TAp63 was sufficient to decrease cell viability, suggesting that it is a critical downstream effector of miR‐130b. In vivo, combined miR‐130b plus CDDP exhibited greater therapeutic efficacy than miR‐130b or CDDP alone. Mice that carried OVCAR8 xenograft tumors and were injected with miR‐130b in 1,2‐dioleoyl‐sn‐glycero‐3‐phosphatidylcholine (DOPC) liposomes had a significant decrease in tumor burden at rates similar to those observed in CDDP‐treated mice, and 20% of DOPC–miR‐130b plus CDDP‐treated mice were living tumor free. Systemic injections of scL–miR‐130b plus CDDP in a clinically tested, tumor‐targeted nanocomplex (scL) improved survival in 60% and complete remissions in 40% of mice that carried HEYA8 xenografts.ConclusionsThe miR‐130b/TAp63 axis is proposed as a new druggable pathway that has the potential to uncover broad‐spectrum therapeutic options for the majority of p53‐altered cancers.
Rare cancers in childhood and adolescence in Brazil: First report of data from 19 population‐based cancer registries
Authors: Balmant Nathalie V. , de Souza Reis Rejane , de Oliveira Santos Marceli , de Camargo Beatriz , Gatta Gemma 
Published: April 2019

BackgroundRare childhood cancer is challenging to define. The Italian Pediatric Rare Tumor (TREP) Study considers rare tumors to include solid malignancies characterized by an annual incidence rate of <2 cases per 1 million and not enrolled in clinical trials. The objective of the current study was to analyze the population incidence rate of rare tumors among children and adolescents (those aged birth‐19 years) in Brazil.MethodsIncidence data were obtained from 19 population‐based cancer registries covering the 5 geographic regions in Brazil. Newly diagnosed cases were selected according to the TREP definition, using the International Classification of Diseases for Oncology. To calculate the crude incidence rate, the numbers of incident children and adolescents with a specific rare cancer were divided by the corresponding person‐years lived for the population aged <20 years during the same period.ResultsTwo tumors had an incidence rate that was >2 cases per 1 million (thyroid and skin cancers) in adolescents only. Several tumors demonstrated variations in incidence across the Brazilian regions. Adrenocortical carcinoma had a high incidence rate (4 cases per 1 million) in the south region among children aged <10 years. Thyroid and skin carcinoma had higher incidence rates in the midwest, southeast, and south regions.ConclusionsDue to the extraordinary rarity of these events, networking is important for improving basic research, clinical studies, and trials. Centralization of diagnosis is the only way to improve the diagnosis and treatment of children affected by these rare diseases. The registration and surveillance of rare pediatric cancers are crucial from a public health point of view, and therefore the quality of registration has to be improved.
One‐Pot Hydrothermal Synthesis of Co3O4/MWCNTs/Graphene Composites with Enhanced Microwave Absorption in Low Frequency Band
Authors: Tao Yu , Yin Pengfei , Zhang Limin , Feng Xing , Wang Jian , Zhang Yi , Wu Wenjuan , Liu Yuntao , Li Shiping , Qiu Zehao 
Published: April 2019

AbstractIn this paper, the Co3O4/MWCNTs/Graphene ternary composite was synthesized by a facile one‐pot hydrothermal method. The crystal structure, microstructure and elementary composition, electromagnetic parameters and microwave absorption property were systemically investigated by the XRD, SEM, TEM and VNA respectively. The results showed that the as‐prepared ternary composite exhibits enhanced absorption property in the frequency range of 0.1–3.0 GHz, which is mainly attributed to the synergistic effects of the dielectric loss and magnetic loss. The enhanced dielectric loss mainly generates from the strong dipole and interfacial polarization of the adherent MWCNTs and embedded graphene fragments, and the enhanced magnetic loss derives from eddy current loss and nature resonance together. The maximum reflection loss of this composite can reach −42.56 dB at 0.39 GHz with a thickness of 5 mm, while the maximum effective absorption bandwidth covers from 0.77 GHz to 1.99 GHz with a relatively thinner thickness of 2 mm. This study provides a facile method to synthesize Co3O4/MWCNTs/Graphene composite with excellent properties that is a potential candidate for microwave absorption in low frequency band.
Reductive Amination/Cyclization of Methyl Levulinate with Aspartic Acid: Towards Renewable Polyesters with a Pendant Lactam Unit
Authors: Bernhard Yann , Pellegrini Sylvain , Bousquet Till , Favrelle Audrey , Pelinski Lydie , Cazaux Frédéric , Gaucher Valérie , Gerbaux Pascal , Zinck Philippe 
Published: April 2019

AbstractEnvironmental regulation and depletion of fossil resources are boosting the search for new polymeric materials produced from biomass. Here, the synthesis of a new diester bearing a pendant lactam unit from methyl levulinate and aspartic acid is reported. The palladium‐catalyzed reductive amination/cyclization sequence was carefully optimized to afford the diacid with high yield (>95 %). In a second step, the compound was esterified to give the corresponding diester. The latter monomer was copolymerized with α–ω linear diols, yielding polyesters with molecular weights up to 20.5 kg mol−1.
Clinical impact of testing for mutations and microRNAs in thyroid nodules
Authors: Sistrunk John Woody , Shifrin Alexander , Frager Marc , Bardales Ricardo H. , Thomas Johnson , Fishman Norman , Goldberg Philip , Guttler Richard , Grant Edward 
Published: April 2019

AbstractBackgroundWe report results of a multicenter clinical experience study examining the likelihood of patients with indeterminate thyroid nodules to undergo surgery or have malignant outcome based on multiplatform combination mutation and microRNA testing (MPT).MethodsMPT assessed mutations in BRAF, HRAS, KRAS, NRAS, and PIK3CA genes, PAX8/PPARγ, RET/PTC1, and RET/PTC3 gene rearrangements, and the expression of 10 microRNAs. Baseline clinical information at the time of MPT and clinical follow‐up records were reviewed for 337 patients, of which 80% had negative MPT results. Kaplan Meier analysis for cumulative probability of survival without having a surgical procedure or malignant diagnosis over the course of patient follow‐up was determined for MPT results of 180 patients, among which only 14% had malignancy.ResultsA negative MPT result in nodules with Bethesda III or IV cytology (2009) conferred a high probability of non‐surgical treatment, with only 11% expected to undergo surgery and a high probability of survival without malignancy (92%) for up to 2 years follow up. A positive MPT result conferred a 57% probability of malignancy and was an independent risk factor for undergoing surgical treatment (Hazard Ratio [HR] 9.2, 95% confidence intervals 5.4‐15.9, P < .0001) and for malignancy (HR 13.4, 95% confidence intervals 4.8‐37.2, P < .0001). For nodules with weak driver mutations, positive microRNA test results supported high risk of cancer while negative results downgraded cancer risk.ConclusionMPT results are predictive of real‐world decisions to surgically treat indeterminate thyroid nodules, with those decisions being appropriately aligned with a patient's risk of malignancy over time.
Reindeer turning maritime: Ice‐locked tundra triggers changes in dietary niche utilization
Authors: Hansen Brage Bremset , Lorentzen Jon Runar , Welker Jeffrey M. , Varpe Øystein , Aanes Ronny , Beumer Larissa Teresa , Pedersen Åshild Ønvik 
Published: April 2019

AbstractThe rapid warming of the Arctic may not only alter species’ abundances and distributions, but likely also the trophic interactions within and between ecosystems. On the high‐arctic tundra, extreme warm spells and associated rain‐on‐snow events in winter can encapsulate the vegetation entirely in ground‐ice (i.e., basal ice) and directly or indirectly affect plants, herbivores, and carnivores. However, the implications of such extreme events for trophic interactions and food‐web ecology are generally far from understood. Here, we show that wild Svalbard reindeer populations increasingly isolated by lack of sea‐ice respond to rain‐on‐snow and ice‐locked pastures by increased kelp consumption. Based on annual population surveys in late winters 2006–2015, the proportion of individual reindeer feeding along the shoreline increased the icier the winter. Stable isotope values (δ34S, δ13C, δ15N) of plants, washed‐ashore kelp, and fresh reindeer feces collected along coast‐inland gradients, confirmed ingestion of marine biomass by the reindeer in the shoreline habitat. Thus, even on remote islands and peninsulas increasingly isolated by sea‐ice loss, effects of climate change may be buffered in part by behavioral plasticity and increased use of resource subsidies. This marine dimension of a terrestrial herbivore's realized foraging niche adds to evidence that global warming significantly alters trophic interactions as well as meta‐ecosystem processes.
Narrow pollen diets are associated with declining Midwestern bumble bee species
Authors: Wood T. J. , Gibbs J. , Graham K. K. , Isaacs R. 
Published: April 2019

AbstractMany species of bumble bee (Bombus) have declined in range and abundance across Europe, the Americas, and Asia, whereas other species have persisted and remain common and widespread. One explanation as to why some species have declined, based primarily on studies of the European bumble bee fauna, is that declining species have relatively narrow pollen‐foraging niches and are less able to use alternative host plants in the absence of their preferred hosts. Though extensively explored in Europe, this hypothesis has not been investigated in North America, in part due to incomplete information on the foraging niche of many species. We selected 12 bumble bee species found in Michigan and quantified their pollen diets using museum specimens. We also extensively resurveyed the state to understand their contemporary status and distribution. Compared to a pre‐2000 baseline, six species remain relatively common and widespread, whereas six species show range contractions of over 50%. There was a significant relationship between dietary breadth and distributional range change, with declined or declining species collecting around one‐third fewer pollen types than stable species. Though there were significant compositional differences, we found no differences in the number of pollen types collected by species with differing tongue lengths. Overall, these results support the hypothesis that species with narrower dietary niches are at greater risk of decline. However, it is not clear if narrow dietary niches are a cause of declines, or if both are driven by an underlying factor such as proximity to the edge of climatic niches. Further research is needed to improve our understanding of dietary niche in bumble bees, and how it interacts with other factors to influence population trajectories of stable and at‐risk species.