bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bombyx mori kynurenine 3‐monooxygenase gene editing and insect molecular breeding using the clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 system
Authors: Hong Jeong Won , Jeong Chan Young , Yu Jeong Hee , Kim Su‐Bae , Kang Sang Kuk , Kim Seong‐Wan , Kim Nam‐Suk , Kim Kee Young , Park Jong Woo 
Published: July 2020

AbstractGenome editing by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated protein (Cas)9, a third‐generation gene scissors, and molecular breeding at the genome level are attracting considerable attention as future breeding techniques. In the present study, genetic and phenotypic analyses were conducted to examine the molecular breeding of Bombyx mori through CRISPR/Cas9‐mediated editing of the kynurenine 3‐monooxygenase (KMO) gene. The synthesized guide RNAs (gRNAs) were analyzed using T7 endonuclease I after introduction into the BM‐N silkworm cell line. To edit the silkworm gene, K1P gRNA, and Cas9 complexes were microinjected into silkworm embryos. After microinjection, the hatching rate and the incidence of mutation were determined as 18.1% and 60%, respectively. Gene mutation was verified in the heterozygous G0 generation, but no phenotypic change was observed; however, certain embryos and moths produced through sib‐mating had significant differences compared to the wild‐type. In successive generations, a distinct phenotypic change was also observed by continuous mating. Thus, although there are limitations in the phenotypic expression in breeding through the induction of deletion mutations, as in the present study, the process is believed to yield successful results within a shorter period compared to traditional breeding and is safer than transgenic technology.
Regimen‐intensity per count‐recovery and hospitalization index: A new tool to assign regimen intensity for AML
Authors: Sorror Mohamed L. , Agarwal Shirali , Othus Megan , Lynch Ylinne , Nyland Jennifer E. , Percival Mary‐Elizabeth , Becker Pamela S. , Appelbaum Frederick R. , Estey Elihu H. 
Published: July 2020

AbstractBackgroundLow‐intensity regimens have been increasingly used to treat older patients with acute myeloid leukemia (AML). Recent studies, however, suggest older patients can tolerate and potentially benefit from intensive chemotherapeutic regimens. The ability to compare the utility of varying regimen intensities in AML is hindered by the lack of a standardized definition of “regimen intensity.”MethodsWe conducted a survey asking AML physicians which of 38 regimens they would consider intensive vs less‐intensive. Electronic medical records of 592 patients receiving many of these regimens were used to design a model characterizing regimens as intensive vs less‐intensive as identified by ≥75% physician consensus. Variables included frequency and length of hospitalizations, intensive care unit admissions, severe gastrointestinal toxicities, time to nadir, and recovery of neutrophil/platelet count.ResultsPhysicians agreed at a rate of 75%‐100% on the assignment of degree of intensity to the majority (n = 28) of these regimens, while the level of agreement was <75% for the remaining 10 regimens (26%). Logistic regression analyses identified number and length of hospitalizations to be significantly associated with intensive regimens and count recovery with less‐intensive regimens. We created the “regimen‐intensity per count‐recovery and hospitalization” (RICH) index with an AUC of 0.87. Independent model validation yielded an AUC of 0.75.ConclusionsWe were able to generate a novel model that defines regimen intensity for many therapies used to treat AML. Results facilitate a future randomized study comparing intensive vs less‐intensive regimens.
Metabolic dysfunction and early‐onset colorectal cancer – how macrophages build the bridge
Authors: Scheurlen Katharina M. , Billeter Adrian T. , O'Brien Stephen J. , Galandiuk Susan 
Published: July 2020

AbstractBackgroundThe incidence of colorectal cancer (CRC) among patients <50 years of age has increased dramatically over the last decades. At the same time, the growing proportion of obese children and adolescents and the increasing proportion of young and obese patients with CRC suggests an association between metabolic dysfunction and carcinogenesis. Tumor‐associated macrophages (TAMs) are able to orchestrate tumor promoting and suppressing mechanisms in CRC. The aim of this review was to discuss the different roles of TAMs in CRC and their phenotype‐specific metabolic pathways to identify potential new targets for CRC treatment.MethodsA literature search was performed using PubMed, Cochrane and Embase to identify studies on TAMs and their metabolism in CRC. The following search terms were used in various combinations: (obesity OR adiposity OR obese) AND (macrophage OR polarization OR macrophage metabolism) AND ((colon cancer*) OR (colon carcinoma) OR (colonic tumor*) OR (colonic neoplasm[MeSH]) OR (rectal cancer*) OR (rectal carcinoma) OR (rectal tumor*) OR (rectal neoplasm[MeSH]) OR (colorectal cancer*) OR (colorectal carcinoma) OR (colorectal tumor*) OR (colorectal neoplasm[MeSH])). Studies including data on the phenotype and metabolism of TAMs in CRC were analyzed.ResultsEvidence for the prognostic utility of macrophage markers in CRC is currently evolving, with a particular role of stage‐dependent cellular metabolism profiles of TAMs. Itaconate is one of the metabolites produced by proinflammatory subtypes of TAMs and it is known to have tumor promoting effects. Metabolic pathways that are involved in macrophage activation and reprogramming play a role in a chronic inflammatory setting, consequently affecting the onset and development of CRC.ConclusionsTumor‐promoting metabolites, such as itaconate, are directly regulating these mechanisms, thereby triggering carcinogenesis. Metabolic reprogramming in TAMs can build a bridge between metabolic dysfunction and the onset and progression of CRC through inflammatory pathways, particularly in younger patients with early‐onset CRC.
Towards Efficient Nonenzymatic DNA Ligation: Comparing Key Parameters for Maximizing Ligation Rates and Yields with Carbodiimide Activation**
Authors: Obianyor Chiamaka , Newnam Gary , Clifton Bryce E. , Grover Martha A. , Hud Nicholas V. 
Published: July 2020

AbstractChemical ligation is an important tool for the generation of synthetic DNA structures, which are used for a wide range of applications. Surprisingly, reported chemical ligation yields can range from 30 to 95 % for the same chemical activating agent and comparable DNA structures. We report a systematic study of DNA ligation by using a well‐defined bimolecular test system and a water‐soluble carbodiimide (EDC) as a phosphate‐activating agent. Our results emphasize the interplay between template‐substrate complex stability and the rates of the chemical steps of ligation, with 3′ phosphate substrates providing yields near 100 % after 24 hours for particularly favorable reaction conditions. Ligation rates are also shown to be sensitive to the identity of the base pairs flanking a nick site, with as much as threefold variation. Finally, the observation that DNA substrates are modified by EDC at rates that can be comparable with ligation rates emphasizes the importance of considering side reactions when designing protocols to maximize ligation yields.
DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells
Authors: Nie Xuekun , Chen Huajiao , Niu Peiguang , Zhu Yanting , Zhou Jintuo , Jiang Li , Li Danyun , Lin Minhua , Chen Zichun , Shi Daohua 
Published: July 2020

AbstractAutophagy is closely related to the formation and development of multiple human tumors including ovarian cancer. As a major regulator of this process, the role of mTOR (mammalian target of rapamycin) has been well proven. Cardamonin, a kind of flavonoid from plants, has effects on induction of autophagy and thus antiproliferation of cancer cells. However, the detailed mechanism remains unclear. DAP1 (death‐associated protein 1) is a proline‐rich protein, which is involved in the regulation of cellular growth and programmed cell death including autophagy and apoptosis. The aim of this study was to investigate whether DAP1 is involved in proliferation inhibition and autophagy induced by cardamonin in tumor cells. Using online bioinformatics tools, we found that DAP1 expression is closely related to the survival of patients with ovarian cancer. Our study showed that autophagy induced by cardamonin was associated with mTOR inhibition, and DAP1 was involved in this process. Silence of DAP1 decreased cell proliferation but enhanced the antiproliferative effect of cardamonin in SKOV3 cells. The level of autophagy was elevated by DAP1 silencing in SKOV3 cells. Notably, cardamonin showed higher autophagy flux in the DAP1 small interfering RNA group. Taken together, our results implied that DAP1 negatively regulates autophagy induced by cardamonin, and it may be a potential target for ovarian cancer therapy.
Full Thermal Switching of Enzymes by Thermoresponsive Poly(2‐oxazoline)‐Based Enzyme Inhibitors
Authors: Hijazi Montasser , Türkmen Esra , Tiller Joerg C. 
Published: July 2020

AbstractControlling the activity of enzymes is an important feature for many processes in medicine, bioanalytics, and biotechnology. So far, it has not been possible to fully switch biocatalysts on and off by thermoresponsive enzyme inhibitors. Herein, we present poly(2‐oxazoline)s with iminodiacetic acid end groups (POx‐IDA) that are lower critical solution temperature (LCST) polymers and thus thermosensitive. They are capable of reversibly inhibiting the activity of horse radish peroxidase and laccase by more than 99 %. Increasing the temperature makes the POx‐IDA precipitate, which leads to 100 % recovery of the enzyme activity. This switching cycle is fully reversible. The LCST of the POx‐IDA can be tuned by varying the polymer composition to generate a wide range of switching windows.
Environmentally Benign, Intrinsically Coordinated, Lithium‐Based Solid Electrolyte with a Modified Purine as Supporting Ligand
Authors: Avasthi Ilesha , Gaganjot  , Katiyar Monica , Verma Sandeep 
Published: July 2020

AbstractBioinspired materials have become increasingly competitive for electronic applications in recent years owing to the environment‐friendly alternatives they offer. The notion of biocompatible solid organic electrolytes addresses the issues concerning potential leakage of corrosive liquids, volatility and flammability of electrolyte solvents. This study presents a new intrinsically coordinated LiI adenine complex that exhibits electrical conductivity as a solid electrolyte capable of self‐sustained supply of LiI ions. It exhibits conductivity through moisture‐assisted LiI ion motion up to 373 K, and possibly by an ion‐hopping mechanism beyond 373 K. This purine‐derived solid electrolyte shows enhanced conductivity and transference number demonstrating the potential of purine‐based ligands and their coordination complexes in interesting materials applications.
Hierarchical Synthesis, Structure, and Photophysical Properties of Gallium‐ and Ruthenium‐Porphyrins with Axially Bonded Azo Ligands
Authors: Gao Yueze , Walter Vroni , Ferguson Michael J. , Tykwinski Rik R. 
Published: July 2020

AbstractThe hierarchical synthesis of three porphyrin and four bisporphyrin derivatives is presented. This strategy relies on the incorporation of linkers based on azo moieties appended with pyridyl and/or acetylenic groups that facilitate axial coordination to Ga‐ and Ru‐metalloporphyrins. These porphyrinic systems allow for a quantitative analysis of the effects of diamagnetic anisotropy (DA) by using 1H NMR spectroscopic and X‐ray crystallographic analyses. A simple power‐law relationship between the proton chemical shift and the distance from the porphyrin core is experimentally outlined, which confirms previous theoretical predictions and shows that the limit of DA is about 2 nm. Photophysical properties of the azo‐linked porphyrins are analyzed by UV/Vis spectroscopy, showing that significant cis–trans isomerization is not observed for azo ligands bound only to Ga‐porphyrins. Incorporation of Ru‐porphyrins to an azo ligand facilitates photoswitching behavior, but the process faces competition from decarbonylation of the Ru‐porphyrin, and appreciable switching is only documented for GaL1Ru.
Understanding the Catalytic Sites of Metal–Nitrogen–Carbon Oxygen Reduction Electrocatalysts
Authors: Chen Ming‐Xi , Tong Lei , Liang Hai‐Wei 
Published: July 2020

AbstractThe development of low‐cost catalysts containing earth‐abundant elements as alternatives to Pt‐based catalysts for the oxygen reduction reaction (ORR) is crucial for the large‐scale commercial application of proton exchange membrane fuel cells (PEMFCs). Nonprecious metal–nitrogen–carbon (M‐N‐C) materials represent the most promising candidates to replace Pt‐based catalysts for PEMFCs applications. However, the high‐temperature pyrolysis process for the preparation of M‐N‐C catalysts frequently leads to high structural heterogeneity, that is, the coexistence of various metal‐containing sites and N‐doped carbon structures. Unfortunately, this impedes the identification of the predominant catalytic active structure, and thus, the further development of highly efficient M‐N‐C catalysts for the ORR. This Minireview, after a brief introduction to the development of M‐N‐C ORR catalysts, focuses on the commonly accepted views of predominant catalytic active structures in M‐N‐C catalysts, including atomically dispersed metal–Nx sites, metal nanoparticles encapsulated with nitrogen‐doped carbon structures, synergistic action between metal–Nx sites and encapsulated metal nanoparticles, and metal‐free nitrogen‐doped carbon structures.
Transition‐Metal‐Catalyzed Cycloaddition Reactions to Access Seven‐Membered Rings
Authors: Trost Barry M. , Zuo Zhijun , Schultz Johnathan E. 
Published: July 2020

AbstractThe efficient and selective synthesis of functionalized seven‐membered rings remains an important pursuit within synthetic organic chemistry, as this motif appears in numerous drug‐like molecules and natural products. Use of cycloaddition reactions remains an attractive approach for their construction within the perspective of atom and step economy. Additionally, the ability to combine multiple components in a single reaction has the potential to allow for efficient combinatorial strategies of diversity‐oriented synthesis. The inherent entropic penalty associated with achieving these transformations has impressively been overcome with development of catalysis, whereby the reaction components can be pre‐organized through activation by transition‐metal‐catalysis. The fine‐tuning of metal/ligand combinations as well as reaction conditions allows for achieving chemo‐, regio‐, diastereo‐ and enantioselectivity in these transformations. Herein, we discuss recent advances in transition‐metal‐catalyzed construction of seven‐membered rings via combination of 2–4 components mediated by a variety of metals. An emphasis is placed on the mechanistic aspects of these transformations to both illustrate the state of the science and to highlight the unique application of novel processes of transition‐metals in these transformations.
Functional Rotaxanes in Catalysis
Authors: Kwamen Carel , Niemeyer Jochen 
Published: July 2020

AbstractMechanically interlocked molecules (MIMs) have gained attention in the field of catalysis due to their unique molecular properties. Central to MIMs, rotaxanes are highly promising and attractive supramolecular catalysts due to their unique three‐dimensional structures and the flexibility of their subcomponents. This Minireview discusses the use of rotaxanes in organocatalysis and transition‐metal catalysis.
Kiss1R Identification and Biodistribution Analysis Employing a Western Ligand Blot and Ligand‐Derivative Stain with a FITC‐Kisspeptin Derivative
Authors: Hasegawa Koki , Maedomari Rika , Sato Younosuke , Gotoh Kumiko , Kudoh Shinji , Kojima Akihiro , Okada Seiji , Ito Takaaki 
Published: July 2020

AbstractIt is not always easy to establish specific antibodies against receptors. Most receptors are hydrophobic and have complicated three‐dimensional structures, making them difficult to use as immunogens. Thus, we developed receptor detection methods with a fluorescein‐labeled ligand as an antibody alternative, which we referred to as a western ligand blot (WLB) and ligand derivative stain (LDS). Kisspeptin receptor (Kiss1R) was detected by its ligand. Kiss1R expression was confirmed in eight human cell lines by the WLB and in four pathological tissues by the LDS. Next, Kiss1R was stained by LDS in organs, revealing Kiss1R expression by [67Ga]Ga‐DOTA‐kisspeptin 10 accumulation. As a result, Kiss1R‐expressing cells in each organ could be stained with fluorescein‐labeled kisspeptin 14 instead of an antibody and observed by light microscopy. The combination of the WLB and LDS allows identification of receptors in tissues, which can be readily applied to target receptor detection by a synthetic ligand derivative.
Why does the CIELAB a* axis point toward magenta instead of red?
Authors: Seymour John 
Published: July 2020

AbstractRed is a basic color. The work of Kay and Berlin on the evolution of color names in languages shows that, after white and black, red is the most basic of color terms. Red plays a key part in Hering's color opponent theory, and is one of the elementary colors in both the Munsell Color system and in the Natural Colour System (NCS). The CIELAB color system has an axis which is sometimes referred to as the red‐green axis. But unique red is about 25° degrees counterclockwise from the positive a* axis. This article answers the question of why this is.
Evaluation of Absolute Oral Bioavailability and Bioequivalence of Ribociclib, a Cyclin‐Dependent Kinase 4/6 Inhibitor, in Healthy Subjects
Authors: Ji Yan , Abdelhady Ahmed M. , Samant Tanay S. , Yang Shu , Rodriguez Lorenc Karen 
Published: July 2020

AbstractRibociclib, a selective and potent cyclin‐dependent kinase 4/6 inhibitor, has demonstrated safety and efficacy in combination with endocrine therapy in hormone receptor‐positive, human epidermal growth factor receptor‐2‐negative advanced breast cancer. In 2 open‐label crossover studies in healthy participants, the absolute bioavailability of a single oral dose of a ribociclib 600‐mg tablet (n = 16) was compared with a single intravenous ribociclib infusion of 150 mg (n = 16), and the bioequivalence of a ribociclib 600‐mg tablet (n = 31) and a ribociclib 600‐mg capsule (n = 31) was evaluated. The pharmacokinetics of ribociclib and its major metabolite, LEQ803, were assessed in both studies. The oral bioavailability of the 600‐mg ribociclib tablet was 65.8% (90% confidence interval [CI], 59.1‐73.2%). The geometric mean systemic clearance of ribociclib was moderate (40.2 L/h; 27.4% intersubject variability [CV%]) compared with hepatic blood flow, and the geometric mean volume of distribution was high (979 L; 25.2 CV%). LEQ803‐to‐ribociclib metabolic ratios were 0.198 for the oral administration and 0.125 for intravenous infusion. Bioequivalence of the tablet and capsule formulations was demonstrated for ribociclib. The geometric mean ratios of maximum concentration and area under the curve from time 0 to last quantifiable concentration and to infinity were 1.01, 1.00, and 0.937, respectively, within the predefined bioequivalence range of 0.80 to 1.25. The median time to reach maximum concentration was 3 hours with both formulations. No serious adverse events were observed in either study.
In Vitro Dissolution and In Vivo Bioequivalence Evaluation of Two Metformin Extended‐Release Tablets
Authors: Zhou Ziye , Wang Chenxiang , Li Min , Lan Qin , Yu Chao , Yu Guoxin , Xia Yan , Chen Huafang , Zhang Xiuhua 
Published: July 2020

AbstractThe objective of the present study was to evaluate the bioequivalence between generic and branded metformin extended‐release (ER) tablets in Chinese subjects. We tested bioequivalence in vitro and in vivo using a comparative dissolution study and a comparative pharmacokinetic trial. Safety assessments were conducted throughout the entire trial period. The dissolution profiles of the generic formulation expressed obvious extended‐release properties, similar to those of the branded formulation (f2 > 60.0%). Consistent with the result of the in vitro study, no remarkable differences were found in terms of pharmacokinetic profiles between generic and branded formulations. The 90% confidence intervals of Ln AUC0‐36 h, Ln AUC0‐∞, and Ln Cmax from generic formulation versus branded formulation were 91.4% to 105.0%, 91.3% to 104.7%, and 101.2% to 119.4%, respectively. During the entire trial period, 4 subjects experienced 11 adverse events. All these were mild and spontaneously resolved. The results obtained from the present study suggest that the generic and branded metformin ER tablets were bioequivalent in Chinese subjects.
Polyanionic Lattice Modifications Leading to High‐Entropy Sodium Ion Conductors: Mathematical Solution of Accessible Compositions
Authors: Tietz Frank , Fronia Carsten 
Published: July 2020

AbstractSodium zirconium double phosphate NaZr2(PO4)3 can be used as a starting point for investigations of high‐entropy materials. Apart from the frequently used approach of partial substitution with four or more different transition metal cations, this class of materials also allows multiple substitutions of the phosphate groups. Herein modifications of the polyanionic lattice are considered and high‐entropy compositions are numerically determined with up to eight elements on the central tetrahedral lattice site of the so‐called NaSICON structure. For this study, the chemical formula was fixed as Na3Zr2(EO4)3 with E=B, Al, Si, P, As, Sb, S, Se and Te. The number of compositions increases exponentially with the increasing number of elements involved and with decreasing equal step size for each element. The maximum number of 237258 compositions is found for Na3Zr2([B,Al,Si,P,As,Sb,S,Se]O4)3 with a step size of 0.1 mol/formula unit. Of this compositional landscape, 143744 compositions fulfil the definitions of high‐entropy materials. The highest entropy factor of ΔSconfig/R=‐2.0405 is attributed to the compositions Na3Zr2(B0.5Al0.6Si0.4P0.3As0.3Sb0.3S0.3Se0.3)O12 and Na3Zr2(B0.6Al0.5Si0.4P0.3As0.3Sb0.3S0.3Se0.3)O12.