bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assemblies of Peptide‐Cytotoxin Conjugates for Tumor‐Homing Chemotherapy
Authors: Wang Jinqiang , Hu Shiqi , Mao Weiwei , Xiang Jiajia , Zhou Zhuxian , Liu Xiangrui , Tang Jianbin , Shen Youqing 
Published: January 2019

AbstractPeptide‐drug conjugates are prodrugs that have the advantages of precise molecular structure and the direct exploitation of tumor‐homing, penetration or the cellular uptake abilities of the peptides such as the neuropilin‐1 receptor targeting peptide. The prodrugs generally have fast blood clearance due to their low molecular weights and thus are made to self‐assemble into nanostructures, preferably nanosized micelles and vesicles for intravenous administration, to slow their renal clearance. However, most peptidyl prodrugs usually form precipitates, irregular nanofibers or gels that are unsuitable for intravenous injection. Herein, a arginine‐glycine‐aspartic acid‐lysine (RGDK) peptide and cytotoxin 7‐ethyl‐10‐hydroxycamptothecin (SN38) are used to synthesize the tumor‐homing prodrugs (SN38‐Peps) and explore their structure–micelle formation relationships. A small library of SN38‐Peps is obtained using different structures of peptides, linkers, and drug conjugation sites, and the factors affecting the assembly of SN38‐Peps as well as the stability of formed micelles are investigated. An optimized SN38‐Pep, (MOM)SN38(20)‐CRGDK, is finally obtained which forms stable micelles with a hydrodynamic diameter around 110 nm and a fixed drug loading content as high as 35%. The micelles show a prolonged blood circulation, significantly enhanced tumor accumulation, and therefore improved anticancer activity as compared to the non‐targeting prodrug and a clinically used anticancer drug.
Deriving Efficient Porous Heteroatom‐Doped Carbon Electrocatalysts for Hydrazine Oxidation from Transition Metal Ions‐Coordinated Casein
Authors: Fragal Vanessa H. , Fragal Elizângela H. , Zhang Tao , Huang Xiaoxi , Cellet Thelma Sley P. , Pereira Guilherme M. , Jitianu Andrei , Rubira Adley F. , Silva Rafael , Asefa Tewodros 
Published: January 2019

AbstractIn this work, the synthesis of high‐performance, metal ion‐imprinted, mesoporous carbon electrocatalysts for hydrazine oxidation reaction (HzOR) using casein or a family of phosphoproteins derived from cow's milk as a precursor is shown. The synthesis is made possible by mixing trace amounts of non‐noble metal ions (Fe3+ or Co2+) with casein and then producing different metal ions‐functionalized casein intermediates, which upon carbonization, followed by acid treatment, lead to metal ion‐imprinted catalytically active sites on the materials. The materials effectively electrocatalyze HzOR with low overpotentials at neutral pH and exhibit among the highest electrocatalytic performances ever reported for carbon catalysts. Their catalytic activities are also better than the corresponding control material, synthesized by carbonization of pure casein and other materials previously reported for HzOR. This work demonstrates a novel synthetic route that transforms an inexpensive protein to highly active carbon‐based electrocatalysts by modifying its surfaces with trace amounts of non‐noble metals. The types of metal ions employed in the synthesis are found to dictate the electrocatalytic activities of the materials. Notably, Fe3+ is found to be more effective than Co2+ in helping the conversion of casein into more electrocatalytically active carbon materials for HzOR.
Oil Core–PEG Shell Nanocarriers for In Vivo MRI Imaging
Authors: Calcagno Vincenzo , Vecchione Raffaele , Quagliariello Vincenzo , Marzola Pasquina , Busato Alice , Giustetto Pierangela , Profeta Martina , Gargiulo Sara , Cicco Chiara Di , Yu Hui , Cassani Marco , Maurea Nicola , Mancini Marcello , Pellegrino Teresa , Netti Paolo A. 
Published: January 2019

AbstractOil‐in‐water emulsions represent a promising carrier for in vivo imaging because of the possibility to convey poorly water‐soluble species. To promote accumulation at the tumor site and prolong circulation time, reduction of carrier size and surface PEGylation plays a fundamental role. In this work a novel, simple method to design an oil‐core/PEG‐shell nanocarrier is reported. A PEG‐shell is grown around a monodisperse oil‐in‐water nanoemulsion with a one‐pot method, using the radical polymerization of poly(ethylene glycol)diacrylate. PEG polymerization is triggered by UV, obtaining a PEG‐shell with tunable thickness. This core–shell nanosystem combines the eluding feature of the PEG with the ability to confine high payloads of lipophilic species. Indeed, the core is successfully loaded with a lipophilic contrast agent, namely super paramagnetic iron oxide nanocubes. Interestingly, it is demonstrated an in vitro and an in vivo MRI response of the nanocapsules. Additionally, when the nanosystem loaded with nanocubes is mixed with a fluorescent contrast agent, indo‐cyanine green, a relevant in vitro photoacoustic effect is observed. Moreover, viability and cellular uptake studies show no significant cell cytotoxicity. These results, together with the choice of low cost materials and the scale up production, make this nanocarrier a potential platform for in vivo imaging.
All‐Sprayed‐Processable, Large‐Area, and Flexible Perovskite/MXene‐Based Photodetector Arrays for Photocommunication
Authors: Deng Wen , Huang Haichao , Jin Huaimin , Li Wen , Chu Xiang , Xiong Da , Yan Wei , Chun Fengjun , Xie Meilin , Luo Chao , Jin Long , Liu Chuanqi , Zhang Haitao , Deng Weili , Yang Weiqing 
Published: January 2019

AbstractFlexible photodetectors (PDs) are attracting more attention due to their promising applications in wearable optoelectronic devices, bendable imaging sensors, and implantable optoelectronics. For the easy‐processable technology of massively fabricating PDs, instead of the expensive and complex high‐vacuum technique, the well‐matched work function of their active materials is essential. Herein, all‐sprayed‐processable and large‐area PDs are demonstrated on common paper based on two‐dimensional (2D) CsPbBr3 nanosheets and conductive Ti3C2Tx (MXene). Ascribed to the superior conductivity of MXene, high crystallinity of 2D CsPbBr3, and their well‐matched work function, the as‐prepared PDs exhibit an outstanding on/off current ratio up to 2.3 × 103 and a remarkable photoresponse as fast as 18 ms. Specifically, the detectivity (D*) of 6.4 × 108 Jones and responsivity (R) of 44.9 mA W−1 under a bias of 10 V are achieved. Besides, after bending 1500 cycles, the as‐prepared PDs can still maintain the excellent flexibility and stability. Based on this, a superior‐quality and large‐area 1665 pixel sensor in 72 cm2 (≈24 units cm−2) is developed, and it can clearly transmit the image of “0” to realize the photocommunication function. This work provides a low‐cost method of massively producing the flexible large‐area PDs for wearable optoelectronic devices and expanded photocommunication.
Large normal alleles of ATXN2 decrease age at onset in transthyretin familial amyloid polyneuropathy Val30Met patients
Authors: Santos Diana , Coelho Teresa , Alves‐Ferreira Miguel , Sequeiros Jorge , Mendonça Denisa , Alonso Isabel , Sousa Alda , Lemos Carolina 
Published: January 2019

ObjectiveTransthyretin (TTR)‐related familial amyloid polyneuropathy (FAP) is an autosomal dominant neurological disease, caused most frequently by a Val30Met (now classified as Val50Met) substitution in TTR. Age at onset (AO) ranges from 19 to 82 years, and variability exists mostly between generations. Unstable oligonucleotide repeats in various genes are the mechanism behind several neurological diseases, found also to act as modifiers for other disorders. Our aim was to investigate whether large normal repeat alleles of 10 genes had a possible modifier effect in AO in Portuguese TTR‐FAP Val30Met families.MethodsWe analyzed 329 Portuguese patients from 123 families. Repeat length (at ATXN1, ATXN2, ATXN3, ATXN7, TBP, ATN1, HTT, JPH3, AR, and DMPK) was assessed by single and multiplex polymerase chain reaction, using fluorescently labeled primers, followed by capillary electrophoresis. We used a family‐centered approach, and generalized estimating equations were used to account for AO correlation between family members.ResultsFor ATXN2, the presence of at least 1 allele longer than 22 CAGs was significantly associated with an earlier onset in TTR‐FAP Val30Met, decreasing mean AO by 6 years (95% confidence interval = −8.81 to −2.19, p = 0.001). No association was found for the remaining repeat loci.InterpretationLength of normal repeats at ATXN2 may modify AO in TTR‐FAP Val30Met and may function as a risk factor. This can be due to the role of ATXN2 in RNA metabolism and as a modulator of various cellular processes, including mitochondrial stress. This may have relevant implications for prognosis and the follow‐up of presymptomatic carriers. ANN NEUROL 2019;85:251–258.
Positiv geladene Nanoaggregate auf Basis eines zwitterionischen Pillar[5]arens zur Bekämpfung von planktonischen Bakterien und zum Abbau von Biofilmen
Authors: Gao Lingyan , Li Mingjun , Ehrmann Svenja , Tu Zhaoxu , Haag Rainer 
Published: January 2019

AbstractBakterielle Biofilme sind schwer auszurotten, da sie weniger anfällig gegen Antibiotika sind und leicht Resistenzen gegen diese entwickeln. Die zeitnahe Entwicklung neuer Materialien, die planktonische Bakterien bekämpfen und bestehende Biofilme abbauen oder gar zerstören können, ist daher dringend geboten. Zur Bewältigung dieser genannten Herausforderungen haben wir ein multifunktionales zwitterionisches Pillar[5]aren entwickelt, das durch Selbstaggregation schwach positiv geladene Nanoaggregate bildet, die antibakterielle Aktivität gegenüber dem gramnegativen Bakterienstamm Escherichia coli (DH5α), sowie gegenüber dem grampositiven Stamm Staphylococcus aureus (SH1000) zeigen. Darüber hinaus kann das zwitterionische Pillar[5]aren bereits vorhandene Escherichia coli (DH5α) Biofilme effizient zerstören und im Biofilm eingeschlossene Bakterien abtöten, bevor sie Resistenzen entwickeln.
In‐Transit Electroextraction of Small‐Molecule Pharmaceuticals from Blood
Authors: Nanthasurasak Pavisara , See Hong Heng , Zhang Min , Guijt Rosanne M. , Breadmore Michael C. 
Published: January 2019

AbstractAn electrokinetic platform was developed for extracting small‐molecule pharmaceuticals from a dried blood spot. Through the exclusion of liquid reagents and use of low field strength (6 V cm−1), the electroextraction of a drug from a dried blood spot, deposited on a polymer inclusion membrane (PIM), could be realised while in transit in the mail. In transit sample preparation provides a potential solution to in situ sample degradation and may accelerate the workflow upon arrival of a patient sample at the analytical facility. The electroextraction method was enabled through our discovery of the use of 15–20 μm thin PIMs as electrophoretic separation medium in absence of liquid reagents. Here, a PIM consisting of cellulose triacetate as polymer base, 2‐nitrophenyl octyl ether as plasticizer and 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide as carrier was used. The PIM, was packaged with two 12 V batteries to supply the separation voltage. A blood spot containing berberine chloride was deposited and dried before the applying the separation potential, allowing for the electroextraction while the packaged device was shipped in internal mail. Upon arrival in the analytical laboratory, the PIM was analysed using a fluorescence microscope with photon multiplier tube, quantifying the berberine extracted away from the sample matrix. This platform represents a new opportunity for processing clinical samples during transport to the laboratory, saving time and manual handling to accelerate the time to result.
A Metal–Organic Supramolecular Box as a Universal Reservoir of UV, WL, and NIR Light for Long‐Persistent Luminescence
Authors: Wang Zheng , Zhu Cheng‐Yi , Yin Shao‐Yun , Wei Zhang‐Wen , Zhang Jian‐Hua , Fan Ya‐Nan , Jiang Ji‐Jun , Pan Mei , Su Cheng‐Yong 
Published: January 2019

AbstractLong persistent luminescence (LPL) materials have a unique photophysical mechanism to store light radiation energy for subsequent release. However, in comparison to the common UV source, white‐light (WL) and near‐infrared (NIR) excited LPL is scarce. Herein we report a metal–organic supramolecular box based on a D–π–A‐type ligand. Owing to the integrated one‐photon absorption (OPA) and two‐photon absorption (TPA) attributes of the ligand, the heavy‐atom effect of the metal center, as well as π‐stacking and J‐aggregation states in the supramolecular assembly, LPL can be triggered by all wavebands from the UV to the NIR region. This novel designed supramolecular kit to afford LPL by both OPA and TPA pathways provides potential applications in anti‐counterfeiting, camouflaging, decorating, and displaying, among others.
Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene
Authors: Zhu Mingchang , Zhao Hongwei , Peng Tingting , Su Junqi , Meng Bo , Qi Zhenzhen , Jia Bing , Feng Yunhui , Gao Enjun 
Published: January 2019

Three novel complexes, [Zn (tib)2·(H2O)2]·(NO3)2 (1), [Co (tib)2]·2NO3 (2) and [Co2(tib)2(btc)]·H2O (3) [H4btc = 1,2,4,5‐benzenetetracarboxylic acid; H2tib = 1,3,5‐tris(1‐imidazolyl)benzene], were synthesized and characterized by single‐crystal X‐ray, IR and elemental analysis. The interaction of these complexes with FS‐DNA (fish sperm DNA) was monitored, and binding constants were determined using UV/Vis, which revealed that they have the ability to bind to FS‐DNA. DNA‐binding constants (K) for the three complexes were 2.2 × 104 m−1, 0.7 × 104 m−1 and 0.09 × 104 m−1, respectively. The interaction capacity of the complexes with FS‐DNA has been investigated by fluorescence spectroscopy. Stern–Volmer quenching plot values for complexes 1, 2 and 3 were 0.3784, 0.1028 and 0.076, respectively. The viscosity measurement suggested that complexes 1, 2 and 3 interact with DNA in an intercalation mode. In addition, anti‐cancer activities of these complexes investigated through MTT assays in vitro indicated that the complexes showed good cytotoxic activity against cancer cell lines. Cytotoxic activity of test complexes against two different cancer cell lines (HeLa and KB cells) showed significant cancer cell inhibition rates. Flow cytometry experiments and morphological apoptosis studies showed that the complexes induced apoptosis of HeLa tumor cell lines. Finally, a further molecular docking technique was employed to confirm the binding of the complexes toward the molecular target DNA.
Microwave‐assisted synthesis of 1‐substituted‐1H‐benzimidazolium salts: Non‐competitive inhibition of human carbonic anhydrase I and II
Authors: Karlık Özgül , Gençer Nahit , Karataş Mert O. , Ergün Adem , Çıkrıkcı Kübra , Arslan Oktay , Alıcı Bülent , Kılıç‐Cıkla Işın , Özdemir Namık 
Published: January 2019

AbstractA series of 1‐substituted‐1H‐benzimidazolium p‐toluenesulfonate salts were synthesized in good yields by the reaction of 1‐substituted benzimidazole derivatives and p‐toluenesulfonic acid under microwave irradiation. Two iodide salts were synthesized by the anion exchange reaction of the corresponding p‐toluenesulfonate salt and NaI. All compounds were characterized by 1H NMR, 13C NMR, IR, LC‐MS spectroscopic methods, and elemental analyses. The crystal structure of 1‐methoxyethyl‐1H‐benzimidazolium p‐toluenesulfonate 2d showed that cation and anion are interconnected by N−H···O and C−H···O hydrogen bonds. All compounds were examined as inhibitor of human carbonic anhydrase (hCA) I and II, and all of them inhibited hCA I and hCA II. Kinetic investigation results revealed that these compounds inhibit hCA I and hCA II in a non‐competitive manner. The iodide salts had higher inhibitory activity than their corresponding p‐toluenesulfonate salts.
Anthracene‐Attached Persistent Tricyclic Aromatic Hydrocarbon Radicals
Authors: Nishiuchi Tomohiko , Ito Ryuoh , Takada Aya , Yasuda Yuri , Nagata Takaya , Stratmann Erik , Kubo Takashi 
Published: January 2019

AbstractAnthracene‐attached tricyclic aromatic hydrocarbon radicals having different central polygons, Ant‐5, Ant‐6, and Ant‐7, were synthesized to evaluate the role of an anthracene substituent group in the stability and reactivity of tricyclic aromatic hydrocarbon radicals. The bulky anthryl group effectively protects a carbon atom with high spin density, resulting in high persistence of the radicals. On the other hand, the combination of the anthryl group and the tricyclic aromatic scaffold makes the molecular structure drastically change from a twisted form to a folded form and an unpaired electron moves into the anthryl moiety, eventually affording a tail‐to‐tail σ‐dimer.
K‐Sample comparisons using propensity analysis
Authors: Jung Sin‐Ho , Chi Sang Ah , Ahn Hyun Joo 
Published: January 2019

AbstractIn this paper, we investigate K‐group comparisons on survival endpoints for observational studies. In clinical databases for observational studies, treatment for patients are chosen with probabilities varying depending on their baseline characteristics. This often results in noncomparable treatment groups because of imbalance in baseline characteristics of patients among treatment groups. In order to overcome this issue, we conduct propensity analysis and match the subjects with similar propensity scores across treatment groups or compare weighted group means (or weighted survival curves for censored outcome variables) using the inverse probability weighting (IPW). To this end, multinomial logistic regression has been a popular propensity analysis method to estimate the weights. We propose to use decision tree method as an alternative propensity analysis due to its simplicity and robustness. We also propose IPW rank statistics, called Dunnett‐type test and ANOVA‐type test, to compare 3 or more treatment groups on survival endpoints. Using simulations, we evaluate the finite sample performance of the weighted rank statistics combined with these propensity analysis methods. We demonstrate these methods with a real data example. The IPW method also allows us for unbiased estimation of population parameters of each treatment group. In this paper, we limit our discussions to survival outcomes, but all the methods can be easily modified for any type of outcomes, such as binary or continuous variables.
Synthesis of New Potential Lipophilic Co‐Drugs of 2‐Chloro‐2′‐deoxyadenosine (Cladribine, 2‐CdA, Mavenclad®, Leustatin®) and 6‐Azauridine (z6U) with Valproic Acid
Authors: Knies Christine , Reuter Hans , Hammerbacher Katharina , Bender Eugenia , Bonaterra Gabriel A. , Kinscherf Ralf , Rosemeyer Helmut 
Published: January 2019

Abstract2‐Chloro‐2′‐deoxyadenosine (cladribine, 1) was acylated with valproic acid (2) under various reaction conditions yielding 2‐chloro‐2′‐deoxy‐3′,5′‐O‐divalproyladenosine (3) as well as the 3′‐O‐ and 5′‐O‐monovalproylated derivatives, 2‐chloro‐2′‐deoxy‐3′‐O‐valproyladenosine (4) and 2‐chloro‐2′‐deoxy‐5′‐O‐valproyladenosine (5), as new co‐drugs. In addition, 6‐azauridine‐2′,3′‐O‐(ethyl levulinate) (8) was valproylated at the 5′‐OH group (→9). All products were characterized by 1H‐ and 13C‐NMR spectroscopy and ESI mass spectrometry. The structure of the by‐product 6 (N‐cyclohexyl‐N‐(cyclohexylcarbamoyl)‐2‐propylpentanamide), formed upon valproylation of cladribine in the presence of N,N‐dimethylaminopyridine and dicyclohexylcarbodiimide, was analyzed by X‐ray crystallography. Cladribine as well as its valproylated co‐drugs were tested upon their cancerostatic/cancerotoxic activity in human astrocytoma/oligodendroglioma GOS‐3 cells, in rat malignant neuro ectodermal BT4Ca cells, as well as in phorbol‐12‐myristate 13‐acetate (PMA)‐differentiated human THP‐1 macrophages. The most important result of these experiments is the finding that only the 3′‐O‐valproylated derivative 4 exhibits a significant antitumor activity while the 5′‐O‐ as well as the 3′,5′‐O‐divalproylated cladribine derivatives 3 and 5 proved to be inactive.
The Crystal Structures of α‐ and β‐F2 Revisited
Authors: Ivlev Sergei I. , Karttunen Antti J. , Hoelzel Markus , Conrad Matthias , Kraus Florian 
Published: January 2019

AbstractThe crystal structures of α‐F2 and β‐F2 have been reinvestigated using neutron powder diffraction. For the low‐temperature phase α‐F2, which is stable below circa 45.6 K, the monoclinic space group C2/c with lattice parameters a=5.4780(12), b=3.2701(7), c=7.2651(17) Å, β=102.088(18)°, V=127.26(5) Å3, mS8, Z=4 at 10 K can now be confirmed. The structure model was significantly improved, allowed for the anisotropic refinement of the F atom, and an F−F bond length of 1.404(12) Å was obtained, which is in excellent agreement with spectroscopic data and high‐level quantum chemical predictions. The high‐temperature phase β‐F2, stable between circa 45.6 K and the melting point of 53.53 K, crystallizes in the cubic primitive space group Pm
n with the lattice parameter a=6.5314(15) Å, V=278.62(11) Å3, cP16, Z=8, at 48 K. β‐F2 is isotypic to γ‐O2 and δ‐N2. The centres of gravity of the F2 molecules are arranged like the atoms in the Cr3Si structure type.
In Vivo Identification of Protein Kinase Substrates by Kinase‐Oriented Substrate Screening (KIOSS)
Authors: Nishioka Tomoki , Amano Mutsuki , Funahashi Yasuhiro , Tsuboi Daisuke , Yamahashi Yukie , Kaibuchi Kozo 
Published: January 2019

AbstractProtein phosphorylation plays a critical role in the regulation of cellular function. Information on protein phosphorylation and the responsible kinases is important for understanding intracellular signaling. A method for in vivo screening of kinase substrates named KIOSS (kinase‐oriented substrate screening) has been developed. This protocol provides a method that utilizes phosphoprotein‐binding modules such as 14‐3‐3 protein, the pin1‐WW domain, and the chek2‐FHA domain as biological filters to successfully enrich phosphorylated proteins related to intracellular signaling rather than housekeeping and/or structural proteins. More than 1000 substrate candidates for PKA, PKC, MAPK, and Rho‐kinase in HeLa cells, as well as phosphorylation downstream of D1R, NMDAR, adenosine A2a receptor, PKA, PKC, MAPK, and Rho‐kinase in mouse brain slice cultures have been identified by this method. An online database named KANPHOS (Kinase‐Associated Neural Phospho‐Signaling) provides the phosphorylation signals identified by these studies, as well as those previously reported in the literature. © 2019 by John Wiley & Sons, Inc.
IL‐23‐ and Imiquimod‐Induced Models of Experimental Psoriasis in Mice
Authors: Singh Tej Pratap , Zhang Howard H. , Hwang Samuel T. , Farber Joshua M. 
Published: January 2019

AbstractGenome‐wide association studies have found that polymorphisms in genes for IL‐23 and its receptor are important in psoriasis, and blocking IL‐23 is an effective therapy in the disease. The use of Aldara™, a cream that contains the TLR7 and TLR8 agonist imiquimod (IMQ), was found to exacerbate psoriasis in some patients with pre‐existing disease. Intradermal injections of IL‐23 and topical application of Aldara/IMQ induce skin inflammation in mice with features similar to psoriasis—including epidermal hyperplasia and accumulation of inflammatory cells in epidermis and dermis—which is mediated by IL‐17A, IL‐22, and other factors implicated in the human disease. Consequently, these models can be used in preclinical studies to investigate the molecular and cellular pathogenesis of psoriasis, as well as in the evaluation of potential therapies. This article provides detailed methodologies for creating and evaluating the IL‐23‐ and Aldara/IMQ‐induced mouse models of psoriasis. The article also provides a protocol for analyzing skin leukocytes by flow cytometry. © 2019 by John Wiley & Sons, Inc.