bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docosapentaenoic acid and lung cancer risk: A Mendelian randomization study
Authors: Liu Jiaqing , Zhou Huaqiang , Zhang Yaxiong , Huang Yan , Fang Wenfeng , Yang Yunpeng , Hong Shaodong , Chen Gang , Zhao Shen , Chen Xi , Zhang Zhonghan , Shen Jiayi , Xian Wei , Zhan Jianhua , Zhao Yuanyuan , Hou Xue , Ma Yuxiang , Zhou Ting , Zhao Hongyun , Zhang Li 
Published: February 2019

AbstractBackgroundObservational studies have shown that excessive dietary fat may be associated with lung carcinogenesis. However, findings from previous studies are inconsistent and it remains unclear whether docosapentaenoic acid (DPA), a kind of polyunsaturated fatty acid, is linked to the risk of lung cancer. The aim of this study is to investigate the causal effect of DPA on lung cancer with Mendelian randomization (MR) method.MethodsWith a two‐sample MR approach, we analyzed the summary data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, 8866 individuals of European ancestry) Consortium and International Lung Cancer Consortium (ILCCO, 11 348 lung cancer cases and 15 861 controls; European ancestry) to assess the possible causal relationship of DPA on the risk of lung cancer.ResultsOur results indicated that genetically predicted higher DPA level has a positive association with lung cancer, where 1% higher DPA was associated with a 2.01‐fold risk of lung cancer (odds ratio [OR]: 2.01, 95% CI = 1.34‐3.01; P = 7.40 × 10−4). Additionally, lung cancer was not a causal factor for DPA. The results of MR‐Egger regression analysis showed that there was no evidence for the presence of directional horizontal pleiotropy.ConclusionsGenetically elevated DPA is positively associated with risk of lung cancer, and more work is needed to investigate the potential mechanisms.
Synthesis and Characterization of Novel Thiazolo[3,2‐a]pyrimidine Derivatives and Evaluation of Antioxidant and Cytotoxic Activities
Authors: Khalilpour Asieh , Asghari Sakineh , Pourshab Maryam 
Published: February 2019

AbstractA series of novel thiazolo[3,2‐a]pyrimidines were synthesized and characterized by FT‐IR, 1H, 13C‐NMR and mass techniques. Their antioxidant activities were investigated by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging assay and the results showed that all the synthesized compounds exhibit good antioxidant activity. In addition, it was found that any substituent on the aromatic ring of the products plays an important role in their antioxidant activity. In vitro cytotoxicity of compounds 4a–4j was investigated using MTT cell viability assay. Among these compounds, 6‐ethyl 2,3‐dimethyl 5‐(4‐chlorophenyl)‐7‐methyl‐2,3‐dihydro‐5H‐[1,3]thiazolo[3,2‐a]pyrimidine‐2,3,6‐tricarboxylate (4e) bearing a chlorine substituent displayed the highest cytotoxic effect (IC50=6.26±0.6 μm) in comparison with doxorubicin (IC50=0.68±0.1 μm) as a standard after 72 h. Therefore, it is assumed that these compounds could be used as effective antioxidant and cytotoxic agents.
A “Quenchergenic” Chemoselective Protein Labeling Strategy
Authors: Addy Partha Sarathi , Zheng Yunan , Italia James S. , Chatterjee Abhishek 
Published: February 2019

AbstractDynamic changes in protein structure can be monitored by using a fluorescent probe and a dark quencher. This approach is contingent upon the ability to precisely introduce a fluorophore/quencher pair into two specific sites of a protein of interest. Despite recent advances, there is continued demand for new and convenient approaches to site‐selectively label proteins with such optical probes. We have recently developed a chemoselectively rapid azo‐coupling reaction (CRACR) for site‐specific protein labeling; it relies on rapid coupling between a genetically encoded 5‐hydroxytryptophan residue and various aromatic diazonium ions. Herein, it is reported that the product of this conjugation reaction, a highly chromophoric biarylazo group, is a potent fluorescence quencher. The absorption properties of this azo product can be tuned by systematically altering the structure of the aryldiazonium species. A particular “quenchergenic” aryldiazonium has been identified that, upon conjugation, efficiently quenches the fluorescence of green fluorescent protein, which is a widely used genetically encoded fluorescent probe that can be terminally attached to target proteins. This fluorophore/quencher pair was used to evaluate the protein‐labeling kinetics of CRACR, as well as to monitor the proteolysis of a fusion protein.
Small‐Molecule Inhibitors of the Proteasome's Regulatory Particle
Authors: Muli Christine S. , Tian Wenzhi , Trader Darci J. 
Published: February 2019

AbstractCells need to synthesize and degrade proteins consistently. Maintaining a balanced level of protein in the cell requires a carefully controlled system and significant energy. Degradation of unwanted or damaged proteins into smaller peptide units can be accomplished by the proteasome. The proteasome is composed of two main subunits. The first is the core particle (20S CP), and within this core particle are three types of threonine proteases. The second is the regulatory complex (19S RP), which has a myriad of activities including recognizing proteins marked for degradation and shuttling the protein into the 20S CP to be degraded. Small‐molecule inhibitors of the 20S CP have been developed and are exceptional treatments for multiple myeloma (MM). 20S CP inhibitors disrupt the protein balance, leading to cellular stress and eventually to cell death. Unfortunately, the 20S CP inhibitors currently available have dose‐limiting off‐target effects and resistance can be acquired rapidly. Herein, we discuss small molecules that have been discovered to interact with the 19S RP subunit or with a protein closely associated with 19S RP activity. These molecules still elicit their toxicity by preventing the proteasome from degrading proteins, but do so through different mechanisms of action.
Activating a Cu/ZnO : Al Catalyst – Much More than Reduction: Decomposition, Self‐Doping and Polymorphism
Authors: Frei Elias , Gaur Abhijeet , Lichtenberg Henning , Heine Christian , Friedrich Matthias , Greiner Mark , Lunkenbein Thomas , Grunwaldt Jan‐Dierk , Schlögl Robert 
Published: February 2019

AbstractThe activation of Cu/ZnO‐based catalysts before their application is a key step and sensitive process enabling the development of the entire catalytic potential. Here, we report on a complementary (soft and hard) in‐situ X‐ray absorption spectroscopy (XAS) study investigating in detail the changes of a Cu/ZnO : Al catalyst upon thermal treatment in reducing atmosphere (10 % H2) at ambient pressure. The spectroscopic features of Cu, Zn and Al are investigated. Beyond the reduction event of the Cu moieties, the role of high temperature carbonate and the Al‐dopant is discussed up to the consequences for the ZnO polymorphism. The stability of the observed effects and thus their catalytic relevance are validated by operando XAS under reverse water gas‐shift conditions.
Insulating Polymer‐Hydrogel Nanocomposite Thin Film ‐ Based Catalytic Electrode for Efficient Oxygen Evolution Reaction
Authors: Divya Madhuri U. , Radhakrishnan T. P. 
Published: February 2019

AbstractThe counter‐intuitive choice of an insulating polymer for embedding electrocatalysts is shown to facilitate a simple and general strategy to fabricate catalytic electrodes for efficient oxygen evolution reaction (OER) during water splitting. The hydrogel characteristics and appreciable swelling of the polymer in aqueous medium are the key enabling factors; electrolyte absorbed in the polymer matrix is likely to be involved in the electrocatalytic process. Nanocomposite thin films of chitosan spin‐cast on common conducting substrates, with an optimal content of NiO and [Ni,Fe]O nanoplates generated through a facile and simple in situ protocol, are shown to effect OER with excellent overpotentials (down to 240 mV at 10 mA/cm2), low Tafel slope, high Faradaic efficiency, appreciable turn‐over frequency, and extended stability with high current density. Preliminary investigations with a range of catalyst‐polymer combinations illustrate the general applicability of the approach.
Design of Luminescent, Heteroleptic, Cyclometalated PtII and PtIV Complexes: Photophysics and Effects of the Cyclometalated Ligands
Authors: Giménez Nora , Lalinde Elena , Lara Rebeca , Moreno M. Teresa 
Published: February 2019

AbstractNeutral pentafluorophenyl benzoquinolinyl PtII [Pt(bzq)(HC^N−κN)(C6F5)] (1 a–g) complexes, bearing nonmetalated N‐heterocyclic HC^N ligands [HC^N=2,5‐diphenyl‐1,3,4‐oxadiazole (Hoxd) a, 2‐(2,4‐difluorophenyl)pyridine (dfppy) b, 2‐phenylbenzo[d]thiazole (pbt) c, 2‐(4‐bromophenyl)benzo[d]thiazole (Br‐pbt) d, 2‐phenylquinoline (pq) e, 2‐thienylpyridine (thpy) f, 1‐(2‐pyridyl)pyrene (pypy) g], and heteroleptic bis(cyclometalated) PtIV fac‐[Pt(bzq)(C^N)(C6F5)Cl] (2 b–g, bzq: benzo[h]quinolinyl) derivatives, generated by oxidation of 1 b–g with PhICl2, are reported. The oxidation reaction of 1 a evolved with formation of the bimetallic PtIV complex syn‐[Pt(bzq)(C6F5)Cl(μ‐OH)]2 3. The crystal structures of 1 a,d,f, 2 b,d,e and 3 were corroborated by X‐ray crystallography. A comparative study of the absorption and photoluminescence properties of the two series of complexes PtII (1) and PtIV (2), supported by time‐dependent DFT calculations (TD‐DFT), is presented. The low‐lying transitions (absorption and emission) of PtII complexes 1 a–e [solution and polystyrene (PS) films] were assigned to the IL/MLCT mixture located on the cyclometalated Pt(bzq) unit, with minor IL′/ML′CT/LL′CT contributions involving the non‐metalated ligand. Complex 1 g, bearing the more delocalized pyridyl pyrene (Hpypy) as an ancillary ligand, shows dual 1ππ* and 3ππ* (Hpypy) emission in fluid CH2Cl2 and dual 3IL/3MLCT [Pt(bzq)] and [3ππ*, Hpypy] phosphorescence at 77 K. Upon oxidation, PtIV complexes 2 b–f display (solution, PS) ligand‐based phosphorescence that arises from the bzq in 2 b (3LC) or from the second C^N ligand in 2 c–f (3L′C) with some 3LL′CT in 2 f. Despite metalation of the pyrenyl group, 2 g exhibits dual emission 1ππ*/3ππ* located on the pypy chromophore.
Synthesis of Annulated Indolines by Reductive Fischer Indolization
Authors: Dierks Anna , Schmidtmann Marc , Christoffers Jens 
Published: February 2019

AbstractCyclic β‐oxoesters and arylhydrazine derivatives were converted at ambient temperature under modified Fischer indolization conditions to furnish annulated indolines with quaternary bridgehead carbon center. Reaction conditions were Brønsted acidic (with CF3CO2H), but also reductive (with Et3SiH). The latter reduced intermediate iminium ions under formation of the 2,3‐dihydroindole product constitutions. Racemic products (13 examples) were obtained as single diastereoisomers with relative cis‐configuration, which was proved in two cases by single‐crystal X‐ray structure analysis. Conversion of 4‐bromo‐1‐indanone‐2‐carboxylate and 4‐bromophenylhydrazine gave indeno[1,2‐b]indolines with either 1‐bromo, 8‐bromo, or 1,8‐dibromo substitution, which were further diversified by Suzuki coupling reactions with several arylboronic acids (nine examples).
Upconverting Carbon Nanodots from Ethylenediaminetetraacetic Acid (EDTA) as Near‐Infrared Activated Phototheranostic Agents
Authors: Ortega‐Liebana M. Carmen , Encabo‐Berzosa M. Mar , Casanova Alvaro , Pereboom M. Desiree , Alda J. Octavio , Hueso Jose L. , Santamaria Jesus 
Published: February 2019

AbstractThis work describes the synthesis of nitrogen‐doped carbon nanodots (CNDs) synthesized from ethylenediaminetetraacetic acid (EDTA) as a precursor and their application as luminescent agents with a dual‐mode theranostic role as near‐infrared (NIR) triggered imaging and photodynamic therapy agents. Interestingly, these fluorescent CNDs are more rapidly and selectively internalized by tumor cells and exhibit very limited cytotoxicity until remotely activated with a NIR illumination source. These CNDs are excellent candidates for phototheranostic purposes, for example, simultaneous imaging and therapy can be carried out on cancer cells by using their luminescent properties and the in situ generation of reactive oxidative species (ROS) upon excitation in the NIR range. In the presence of CNDs, NIR remote activation induces the in vitro killing of U251MG cells. Through the use of flow imaging cytometry, we have been able to successfully map and quantify the different types of cell deaths induced by the presence of intracellular superoxide anions (.O2−) and hydrogen peroxide (H2O2) ROS generated in situ upon NIR irradiation.
A Visibly Observable, Programmable Supramolecular Logic Platform and Its Application in Smart Thiols Sensing
Authors: Chen Jianchi , Yang Shu , Yang Chunrong , Li Jicheng , Huang Dan , Lin Xiao , Guo Chen , Zhou Qiuju , Yang Qianfan , Tang Yalin 
Published: February 2019

AbstractMolecular computation is increasingly attractive as a tool for medical and biological research because of its programmability and controllability. Herein, a novel visibly observable supramolecular system that can execute multi‐level logic functions on a uniform platform was constructed. By employing some programming factors, we succeeded in not only constructing a whole set of contrary logic pairs, but also building up a logic network that can implement advanced functions. Further, the platform is applied to sense thiols in specific environments. The developed method can efficiently filter signals of thiols in intracellular conditions and measure cysteine levels quantitatively in serum conditions. The visual readout makes the method particularly suitable for point‐of‐care testing. The supramolecule‐based platform illustrates not only an incremental advance for the construction of programmable molecular logic systems, but also viable applications in intelligent thiol analysis.
Fully Automated Synthesis and Evaluation of [18F]BPAM121: Potential of an AMPA Receptor Positive Allosteric Modulator as PET Radiotracer
Authors: Manos‐Turvey Alexandra , Becker Guillaume , Francotte Pierre , Serrano Maria Elisa , Luxen André , Pirotte Bernard , Plenevaux Alain , Lemaire Christian 
Published: February 2019

AbstractAlzheimer's disease (AD) remains a significant burden on society. In the search for new AD drugs, modulators of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs) are of particular interest, as loss of synaptic AMPARs has been linked to AD learning and memory deficits. Previously reported fluorine‐containing BPAM121, an AMPA positive allosteric modulator (pam) with high activity, low toxicity, and slow metabolism, was considered to be a perfect 18F‐labeled candidate for positron emission tomography (PET) AD diagnostic investigations. For the preclinical use of this compound, an automated synthesis avoiding human radiation exposure was developed. The detailed production of [18F]BPAM121 in relatively high quantity using a commercial FASTlab synthesizer from GE Healthcare coupled with a full set of quality controls is presented, along with procedures for the synthesis of the tosylated precursor and the fluorinated reference. To evaluate the clinical usefulness of [18F]BPAM121 as a potential AD diagnostic, some in vivo studies in mice were then realized, alongside blocking and competition studies.
Paraneoplastic syndrome in neuroendocrine breast cancer: A case report
Authors: Levenbaum Erica , Ruffolo Luis I. , Balceniuk Mark D. , Peacock James , Prieto Peter A. 
Published: February 2019

AbstractBackgroundParaneoplastic syndromes are rare manifestations of underlying malignancies, most commonly small cell lung cancer and invasive ductal carcinoma of the breast.CaseWe present a case of anti‐AMPA receptor paraneoplastic limbic encephalitis, a specific paraneoplastic syndrome, in a woman with neuroendocrine breast cancer. Her condition improved with surgical resection and chemotherapy.ConclusionThis is the first known case of anti‐AMPA receptor paraneoplastic limbic encephalitis in a patient with primary neuroendocrine breast cancer.
Combinatorial BRD4 and AURKA inhibition is synergistic against preclinical models of Ewing sarcoma
Authors: Tomino Laura , Bopp Emily , Felgenhauer Joshua , Selich‐Anderson Julia , Shah Nilay 
Published: February 2019

AbstractBackgroundEwing sarcoma (ES), a bone cancer affecting children, adolescents, and young adults, is driven by the EWS‐FLI1 fusion protein in the majority of cases, but the mechanisms of tumorigenesis are still being elucidated. Consequentially, therapeutic advances have been limited in the last 25 years. Two therapeutic targets have been recently examined. Aurora kinase A (AURKA) promotes cell cycling and posttranslational stabilization of the oncoprotein MYC, while bromodomain‐containing protein 4 (BRD4) promotes gene expression epigenetically. Studies of AURKA and BRD4 inhibitors showed some impairment of tumorigenesis in ES preclinical models, but this efficacy was limited in single‐agent use. AURKA and BRD4 activate common oncogenic pathways through different mechanisms, so we hypothesized dual inhibition would be synergistic against tumorigenesis.Aims(a) Define the synergistic antineoplastic effects of BRD4 inhibitor I‐BET151 and AURKA inhibitor alisertib against ES cell lines in vitro. (b) Confirm the mechanism of activity of each agent in these cell line models. (c) Define the efficacy of I‐BET 151 and alisertib alone and in combinations with each other, and with the chemotherapeutic drug vincristine against ES tumor xenografts in vivo.Methods and resultsI‐BET151 and alisertib synergistically inhibit viability in ES cell lines SK‐ES, TC71, and ES2 in vitro. Alisertib alone upregulates transcriptional expression of its targets, but combined use of I‐BET151 mitigates that upregulation, likely contributing to the drug synergy and downregulating RNA and protein expression of key oncogenic pathways as shown by RT‐qPCR and western blot. Alisertib and I‐BET151 significantly prolong survival in three ES xenograft models in vivo, and this efficacy is augmented by the addition of vincristine.ConclusionDual targeting of oncogenic drivers in ES epigenetically and posttranslationally, specifically by use of BRD4 and AURKA inhibitors, may have significant clinical efficacy in ES alone and/or in combination with current chemotherapy regimens.
High‐Throughput Yeast One‐Hybrid Screens Using a Cell Surface gLUC Reporter
Authors: Li Zheng , Bonaldi Katia , Kang S. Earl , Pruneda‐Paz Jose L. 
Published: February 2019

AbstractGene‐centered yeast one‐hybrid (Y1H) screens using arrayed genome‐wide transcription factor (TF) clone collections provide a simple and effective strategy to identify TF‐promoter interactions using a DNA fragment as bait. In an effort to improve the assay we recently developed a Y1H system that uses a cell surface Gaussia luciferase reporter (gLUC59). Compared to other available methods, this luciferase‐based strategy requires a shorter processing time, enhances the throughput and improves result analysis of gene‐centered Y1H screens. Here, we described the procedure to perform high‐throughput screens using this novel strategy, which involves a protocol for mating two haploid yeast strains carrying an arrayed TF clone collection and a promoter::gLUC59 reporter, respectively, and a protocol for analyzing gLUC59 activity in the resulting diploid cells. © 2019 by John Wiley & Sons, Inc.
Orthodontic screening and treatment timing in preschoolers
Authors: Grippaudo Cristina , Paolantonio Ester Giulia , Luzzi Valeria , Manai Alice , La Torre Giuseppe , Polimeni Antonella 
Published: February 2019

AbstractDental and stomatologic problems in childhood need to be diagnosed and managed with multidisciplinary protocols focusing around the children an appropriate prevention, diagnosis, and care program. Therefore, it is paramount to avail of screening tools that provide an indication of in‐depth multidisciplinary diagnostic flow. The aim of this study is to detect and evaluate malocclusion problems and predisposing factors in an Italian preschooler population. Design‐calibrated operators detected data through examination of 1,405 children (706 males and 699 females) aged between 2 and 7 years, in one hospital in Rome and in kindergartens of several Italian cities. Data were collected following Risk of Malocclusion Assessment index criteria. Pearson's chi‐square test (with continuity correction) and Fisher's exact test were the statistical tests conducted (P < 0.05). Grade 2 (49.6%) and 4 (21.7%), followed by grade 1 (17.1%), grade 3 (9.3%), and finally grade 5 (2.3%) are the most represented degrees. 53.6% of the cases have a high risk, whereas 32.2% has a low risk and 14.9% has a moderate risk. The risk‐degree correlation is statistically significant (P < 0.005). Flawed habits and oral breathing are present in more than a quarter of children. Findings of the study highlighted that early multidisciplinary approach, as well as orthodontic visits and screening in childhood, is necessary to promote normal growth and development of the face and the elimination of potential interferences that may harm these processes.
Manganese‐Catalyzed Selective Upgrading of Ethanol with Methanol into Isobutanol
Authors: Liu Yaqian , Shao Zhihui , Wang Yujie , Xu Lijin , Yu Zhiyong , Liu Qiang 
Published: February 2019

AbstractIsobutanol serves as an ideal gasoline additive owing to its good compatibility with current engine technology, high energy density, and high octane number. Herein, an efficient and selective Mn‐catalyzed upgrading of ethanol with methanol into isobutanol is reported. This is the first example of deoxygenative coupling of lower alcohols to isobutanol by using a homogeneous non‐noble‐metal catalyst. This transformation proceeded at very low catalyst loading with a high turnover number (9233) and up to 96 % isobutanol selectivity.
Electrochemical Reduction of CO2 by SnOx Nanosheets Anchored on Multiwalled Carbon Nanotubes with Tunable Functional Groups
Authors: Zhang Qi , Zhang Yanxing , Mao Jianfeng , Liu Junyu , Zhou Yue , Guay Daniel , Qiao Jinli 
Published: February 2019

AbstractSn‐based electrocatalysts are promising for the electrochemical CO2 reduction reaction (CO2RR), but suffer from poor activity and selectivity. A hierarchical structure composed of ultrathin SnOx nanosheets anchored on the surface of the commercial multiwalled carbon nanotubes (MWCNTs) is synthesized by a simple hydrothermal process. The electrocatalytic performance can be further tuned by functionalization of the MWCNTs with COOH, NH2, and OH groups. Both SnOx@MWCNTs−COOH and SnOx@MWCNTs−NH2 show excellent catalytic activity for CO2RR with nearly 100 % selectivity for C1 products (formate and CO). SnOx@MWCNTs−COOH has favorable formate selectivity with a remarkably high faradaic efficiency (FE) of 77 % at −1.25 V versus standard hydrogen electrode (SHE) and a low overpotential of 246 mV. However, SnOx@MWCNTs−NH2 manifests increased selectivity for CO with higher current density. Density functional theory calculations and experimental studies demonstrate that the interaction between Sn species and functional groups play an important role in the tuning of the catalytic activity and selectivity of these functionalized electrocatalysts. SnOx@MWCNTs−COOH and SnOx@MWCNTs−NH2 both effectively inhibit the hydrogen evolution reaction and prove stable without any significant degradation over 20 h of continuous electrolysis at −1.25 V versus SHE.