bluuebunny/crossref_metadata_2025 huggingface dataset:
Selenium‐Doped Carbon Quantum Dots Act as Broad‐Spectrum Antioxidants for Acute Kidney Injury Management
Authors: Rosenkrans Zachary T. , Sun Tuanwei , Jiang Dawei , Chen Weiyu , Barnhart Todd E. , Zhang Ziyi , Ferreira Carolina A. , Wang Xudong , Engle Jonathan W. , Huang Peng , Cai Weibo
Published: April 2020

The manifestation of acute kidney injury (AKI) is associated with poor patient outcomes, with treatment options limited to hydration or renal replacement therapies. The onset of AKI is often associated with a surfeit of reactive oxygen species. Here, it is shown that selenium‐doped carbon quantum dots (SeCQDs) have broad‐spectrum antioxidant properties and prominent renal accumulation in both healthy and AKI mice. Due to these properties, SeCQDs treat or prevent two clinically relevant cases of AKI induced in murine models by either rhabdomyolysis or cisplatin using only 1 or 50 µg per mouse, respectively. The attenuation of AKI in both models is confirmed by blood serum measurements, kidney tissue staining, and relevant biomarkers. The therapeutic efficacy of SeCQDs exceeds amifostine, a drug approved by the Food and Drug Administration that also acts by scavenging free radicals. The findings indicate that SeCQDs show great potential as a treatment option for AKI and possibly other ROS‐related diseases.
Recent Progress in Electrocatalysts for Acidic Water Oxidation
Authors: Lei Zhanwu , Wang Tanyuan , Zhao Bote , Cai Wenbin , Liu Yang , Jiao Shuhong , Li Qing , Cao Ruiguo , Liu Meilin
Published: April 2020

Hydrogen is a clean and renewable energy carrier for powering future transportation and other applications. Water electrolysis is a promising option for hydrogen production from renewable resources such as wind and solar energy. To date, tremendous efforts have been devoted to the development of electrocatalysts and membranes for water electrolysis technology. In principle, water electrolysis in acidic media has several advantages over that in alkaline media, including favorable reaction kinetics, easy product separation, and low operating pressure. However, acidic water electrolysis poses higher requirements for the catalysts, especially the ones for the oxygen evolution reaction. It is a grand challenge to develop highly active, durable, and cost‐effective catalysts to replace precious metal catalysts for acidic water oxidation. In this article, an overview is presented of the latest developments in design and synthesis of electrocatalysts for acidic water oxidation, emphasizing new strategies for achieving high electrocatalytic activity while maintaining excellent durability at low cost. In particular, the reaction pathways and intermediates are discussed in detail to gain deeper insight into the oxygen evolution reaction mechanism, which is vital to rational design of more efficient electrocatalysts. Further, the remaining scientific challenges and possible strategies to overcome them are outlined, together with perspectives for future‐generation electrocatalysts that exploit nanoscale materials for water electrolysis.
Stretchable and Wearable Resistive Switching Random‐Access Memory
Authors: Shi Qiuwei , Wang Jiangxin , Aziz Izzat , Lee Pooi See
Published: April 2020

In the era of big data, with the development and application of 5G technology, artificial intelligence technology, and wearable electronics, the acquisition, storage, search, sharing, analysis, and even visual presentation require huge amounts of data in storage and processing at any time. This propounds a strong demand for the stretchable and wearable memory devices with ultrafast switching, high density, and high energy efficiency. Herein, an overview of the advanced progresses made on developing stretchable resistive switching random‐access memory (RRAM) is presented, concentrating on the fundamental components, materials selection principles, and configuration design strategies. The basic electrical and mechanical properties of stretchable components to meet the functionality of memory storage are summarized. Novel materials with the intrinsically stretchable features toward the realization of stretchable RRAM are discussed. Ingenious configuration design strategies to obtain stretchable RRAM are evaluated. Finally, the challenges and perspectives for the practical applications of stretchable RRAM are also addressed. Some helpful guidelines are provided in promoting the development on stretchable and wearable RRAM for making deployable and portable artificial intelligence and smart devices.
Enantioselektive Synthese von 3‐Fluorchromanen durch Iod(I)/Iod(III)‐Katalyse
Authors: Sarie Jérôme C. , Thiehoff Christian , Neufeld Jessica , Daniliuc Constantin G. , Gilmour Ryan
Published: April 2020

Das Chromangerüst findet sich in einer Vielzahl von kleinen, bioaktiven Molekülen, in denen die 3‐Position häufig oxidiert wird. Motiviert durch die Wichtigkeit dieser Position für die Wirksamkeit sowie die Bedeutung der Bioisosterie in der Wirkstoffforschung wurde eine Iod(I)/Iod(III)‐Katalysestrategie für den Zugang zu enantiomerenangereicherten 3‐Fluorchromanen entwickelt (bis zu 7:93 e.r.). Die In‐situ‐Erzeugung von ArIF2 ermöglicht die direkte Fluorzyklisierung von Allylphenylethern, um neue Molekülgerüste zu erzeugen, die den stereoelektronischen gauche‐Effekt zeigen. Mechanistische Untersuchungen unter Verwendung von deuterierten Substraten bestätigen einen stereospezifischen Prozess, der mit einem Reaktionsverlauf des Typs IIinv übereinstimmt.
Effiziente Umwandlung von Licht in chemische Energie: Gerichtete, chirale Photoschalter mit sehr hohen Quantenausbeuten
Authors: Moormann Widukind , Tellkamp Tobias , Stadler Eduard , Röhricht Fynn , Näther Christian , Puttreddy Rakesh , Rissanen Kari , Gescheidt Georg , Herges Rainer
Published: April 2020

Photochrome Systeme werden verwendet, um verschiedenste technische Funktionen wie z. B. Konversion von Lichtenergie, molekulare Motoren, Pumpen, Aktuatoren und Sensoren zu realisieren. Essentiell für praktischen Anwendungen sind eine effiziente Umwandlung von Licht in chemische Energie, eine starre Struktur für die Übertragung der molekularen Bewegung auf die Umgebung und eine gerichtete Bewegung während der Isomerisierung. Wir präsentieren einen neuen Typ eines photochromen Systems (Diindandiazocin), welches sichtbares Licht mit einer Effizienz von 18 % in chemische Energie umwandelt. Die Quantenausbeuten sind außerordentlich hoch mit >70 % für die cis‐trans‐Isomerisierung und 90 % für die Rückreaktion und somit höher als im biochemischen System Rhodopsin (64 %). Zwei Diastereomere (meso und Racemat) konnten in einer nur zweistufigen Synthese mit hohen Ausbeuten erhalten werden. Beide Isomere sind gerichtete Schalter mit hohen Umsatzraten (76–99 %), welche selbst nach mehreren tausend Schaltzyklen keine Ermüdung aufzeigten.
Efficient Conversion of Light to Chemical Energy: Directional, Chiral Photoswitches with Very High Quantum Yields
Authors: Moormann Widukind , Tellkamp Tobias , Stadler Eduard , Röhricht Fynn , Näther Christian , Puttreddy Rakesh , Rissanen Kari , Gescheidt Georg , Herges Rainer
Published: April 2020

Photochromic systems have been used to achieve a number of engineering functions such as light energy conversion, molecular motors, pumps, actuators, and sensors. Key to practical applications is a high efficiency in the conversion of light to chemical energy, a rigid structure for the transmission of force to the environment, and directed motion during isomerization. We present a novel type of photochromic system (diindane diazocines) that converts visible light with an efficiency of 18 % to chemical energy. Quantum yields are exceptionally high with >70 % for the cis–trans isomerization and 90 % for the back‐reaction and thus higher than the biochemical system rhodopsin (64 %). Two diastereomers (meso and racemate) were obtained in only two steps in high yields. Both isomers are directional switches with high conversion rates (76–99 %). No fatigue was observed after several thousands of switching cycles in both systems.
RNA interference‐mediated control of cigarette beetle, Lasioderma serricorne
Authors: Koo Jinmo , Chereddy Shankar C. R. R. , Palli Subba R.
Published: April 2020

The cigarette beetle (CB; Lasioderma serricorne) is a pest on many stored products including tobacco. Fumigation is the common control method currently used. However, the options for controlling this pest are limited, due to resistance issues and phasing out of currently used chemical insecticides. Here, we evaluated RNA interference (RNAi) as a potential method for controlling the CB. RNA isolated from different stages was sequenced and assembled into a transcriptome. The CB RNA sequences showed the highest homology with those in the red flour beetle, Tribolium castaneum. Orthologs of proteins known to function in RNAi pathway were identified in the CB transcriptome, suggesting that RNAi may work well in this insect. Also, 32P‐labeled double‐stranded RNA (dsRNA) injected into CB larvae and adults was processed to small interference RNAs. We selected 12 genes that were shown to be the effective RNAi targets in T. castaneum and other insects and identified orthologs of them in the CB by searching its transcriptome. Injection of dsRNA targeting genes coding for GAWKY, Kinesin, Sec23, SNF7, and 26S proteasome subunit 6B into the CB larvae caused 100% mortality. Feeding dsRNA targeting SNF7 and 26S proteasome subunit 6B by sucrose droplet assay induced more than 90% mortality, which is 1.8 times higher than the mortality induced by dsGFP control (53%). These data demonstrate an efficient RNAi response in CB, suggesting that RNAi could be developed as an efficient method to control this pest.
Subphysiological temperature induces pervasive alternative splicing in Chinese hamster ovary cells
Authors: Tzani Ioanna , Monger Craig , Motheramgari Krishna , Gallagher Clair , Hagan Ryan , Kelly Paul , Costello Alan , Meiller Justine , Floris Patrick , Zhang Lin , Clynes Martin , Bones Jonathan , Barron Niall , Clarke Colin
Published: April 2020

RNA sequencing (RNASeq) has been widely used to associate alterations in Chinese hamster ovary (CHO) cell gene expression with bioprocess phenotypes; however, alternative messenger RNA (mRNA) splicing, has thus far, received little attention. In this study, we utilized RNASeq for transcriptomic analysis of a monoclonal antibody (mAb) producing CHO K1 cell line subjected to a temperature shift. More than 2,465 instances of differential splicing were observed 24 hr after the reduction of cell culture temperature. A total of 1,197 of these alternative splicing events were identified in genes where no changes in abundance were detected by standard differential expression analysis. Ten examples of alternative splicing were selected for independent validation using quantitative polymerase chain reaction in the mAb‐producing CHO K1 cell line used for RNASeq and a further two CHO K1 cell lines. This analysis provided evidence that exon skipping and mutually exclusive splicing events occur in genes linked to the cellular response to changes in temperature and mitochondrial function. While further work is required to determine the impact of these changes in mRNA sequence on cellular phenotype, this study demonstrates that alternative splicing analysis can be utilized to gain a deeper understanding of post‐transcriptional regulation in CHO cells during biopharmaceutical production.
Pharmacokinetic study of tanshinol and ligustrazine in rat plasma after intravenous administration of tanshinol and Danshen Chuanxiongqin Injection
Authors: Jiao Weijie , Lei Zhen , Zhao Xu , Wang Kun , Ma Ailing , Du Lei , Hou Ruiying , Han Jing , Chen Meng
Published: April 2020

To investigate the effect of ligustrazine on the pharmacokinetic profile of tanshinol after intravenous administration in rats, a sensitive liquid chromatography tandem mass spectrometry method was developed and validated for quantitative determination of tanshinol and ligustrazine in rat plasma. After prepared by protein precipitation, the analytes were separated on a Waters Acquity HSS T3 column (100 × 2.1 mm, 1.8μm) and eluted by 0.1% formic acid in water and acetonitrile at a flow rate of 0.4 ml/min. The precursor–product ion transitions were m/z 197.0 → 135.0 for tanshinol, m/z 417.1 → 255.1 for liquiritin (internal standard) in negative ion mode and m/z 137.1 → 55.0 for ligustrazine in positive ion mode. To avoid the interference of tanshinol metabolite transformation, the stability of analytes in samples collected after administration was assessed. The validated method was successfully applied to a pharmacokinetic study after intravenous administration of single tanshinol and Danshen Chuanxiongqin Injection. After Danshen Chuanxiongqin injection administration, the values of elimination half‐time, area under the concentration–time curve and Co were 0.36 ± 0.13 h, 1.29 ± 0.37 μg/ml h and 10.51 ± 2.58 μg/ml for male rats, respectively. In the single tanshinol group, the corresponding values were 0.56 ± 0.24 h, 1.85 ± 0.44 μg/ml h and 14.11 ± 2.26 μg/ml for male rats—30–40% higher than those for the Danshen Chuanxiongqin Injection group. There was a significant different between male and female rats. This study provided information on the influence of ligustrazine on the pharmacokinetic characteristics of tanshinol after intravenous administration of Danshen Chuanxiongqin Injection in rats, which will be helpful for its clinical application.
Fluorodeoxyglucose positron emission tomography/computed tomography identifying pericardial metastasis from early‐stage p16‐positive oropharyngeal cancer
Authors: Shim Hye‐kyung , Kim Mi Ra , Lee Hongje
Published: April 2020

Pericardial metastasis from HPV‐positive oropharyngeal squamous cell carcinoma (OPSCC) without local recurrence is extremely rare. We report about a 69‐year‐old man exhibiting pericardial metastasis on positron emission tomography/computed tomography (PET/CT). There are currently no reports on the use of PET/CT in patients with pericardial metastasis from p16‐positive OPSCCs.
Missed bladder rupture following vaginal delivery: Possible role of assessing ascitic fluid creatinine levels?
Authors: Hadian Babak , Nazarpoor Samad , Garshasebi Mohammad , Zafar Mohtashami Azita
Published: April 2020

Bladder injury is the most common urological trauma following the gynecological procedure. Normal vaginal delivery candidates with unresponsive and prolonged ascites and bladder‐emptying complaints should be examined for bladder rupture. We also suggest measurement of ascitic fluid creatinine levels in these patients.
Conformation Control of Conjugated Polymers
Authors: Yu Zi‐Di , Lu Yang , Wang Jie‐Yu , Pei Jian
Published: April 2020

In the past few decades, conjugated polymers have aroused extensive interest in organic electronic applications. The electrical performance of conjugated polymers has a close relationship with their backbone conformation. The conformation of the polymer backbone strongly affects the πelectron delocalization along polymer chains, the energy band gap, interchain interactions, and further affects charge transport properties. To realize a rigid coplanar backbone that usually possesses efficient intrachain charge transport properties and enhanced π–π stackings, such conformation control becomes a useful strategy to achieve high‐performance (semi)conducting polymers. This minireview summarizes the most important polymer structures through conformation control at the molecular level, and then divides these rigid coplanar conjugated polymers into three categories: 1) noncovalent interactions locked conjugated polymers; 2) double‐bond linked conjugated polymers; 3) ladder conjugated polymers. The effect of the conformation control on physical nature, optoelectronic properties, and their device performance is also discussed, as well as the challenges of chemical synthesis and structural characterization.
Controlling the Length of Cooperative Supramolecular Polymers with Chain Cappers
Authors: ter Huurne Gijs M. , Chidchob Pongphak , Long Augustin , Martinez Alexandre , Palmans Anja R. A. , Vantomme Ghislaine
Published: April 2020

The design and the characterization of supramolecular additives to control the chain length of benzene‐1,3,5‐tricarboxamide (BTA) cooperative supramolecular polymers under thermodynamic equilibrium is unraveled. These additives act as chain cappers of supramolecular polymers and feature one face as reactive as the BTA discotic to interact strongly with the polymer end, whereas the other face is nonreactive and therefore impedes further polymerization. Such a design requires fine tuning of the conformational preorganization of the amides and the steric hindrance of the motif. The chain cappers studied are monotopic derivatives of BTA, modified by partial N‐methylation of the amides or by positioning of a bulky cyclotriveratrylene cage on one face of the BTA unit. This study not only clarifies the interplay between structural variations and supramolecular interactions, but it also highlights the necessity to combine orthogonal characterization methods, spectroscopy and light scattering, to elucidate the structures and compositions of supramolecular systems.
Allylic and Allenylic Dearomatization of Indoles Promoted by Graphene Oxide by Covalent Grafting Activation Mode
Authors: Lombardi Lorenzo , Bellini Daniele , Bottoni Andrea , Calvaresi Matteo , Monari Magda , Kovtun Alessandro , Palermo Vincenzo , Melucci Manuela , Bandini Marco
Published: April 2020

The site‐selective allylative and allenylative dearomatization of indoles with alcohols was performed under carbocatalytic regime in the presence of graphene oxide (GO, 10 wt % loading) as the promoter. Metal‐free conditions, absence of stoichiometric additive, environmentally friendly conditions (H2O/CH3CN, 55 °C, 6 h), broad substrate scope (33 examples, yield up to 92 %) and excellent site‐ and stereoselectivity characterize the present methodology. Moreover, a covalent activation model exerted by GO functionalities was corroborated by spectroscopic, experimental and computational evidences. Recovering and regeneration of the GO catalyst through simple acidic treatment was also documented.
Enantiomerically Pure Tetravalent Neptunium Amidinates: Synthesis and Characterization
Authors: Fichter Sebastian , Kaufmann Sebastian , Kaden Peter , Brunner Tobias S. , Stumpf Thorsten , Roesky Peter W. , März Juliane
Published: April 2020

The synthesis of a tetravalent neptunium amidinate [NpCl((S)‐PEBA)3] (1) ((S)‐PEBA=(S,S)‐N,N′‐bis‐(1‐phenylethyl)‐benzamidinate) is reported. This complex represents the first structurally characterized enantiopure transuranic compound. Reactivity studies with halide/pseudohalides yielding [NpX((S)‐PEBA)3] (X=F (2), Br (3), N3 (4)) have shown that the chirality‐at‐metal is preserved for all compounds in the solid state. Furthermore, they represent an unprecedented example of a structurally characterized metal–organic Np complex featuring a Np−Br (3) bond. In addition, 4 is the only reported tetravalent transuranic azide. All compounds were additionally characterized in solution using para‐magnetic NMR spectroscopy showing an expected C3‐symmetry at low temperatures.
Folding Assessment of Incorporation of Noncanonical Amino Acids Facilitates Expansion of Functional‐Group Diversity for Enzyme Engineering
Authors: Drienovská Ivana , Gajdoš Matúš , Kindler Alexia , Takhtehchian Mahsa , Darnhofer Barbara , Birner‐Gruenberger Ruth , Dörr Mark , Bornscheuer Uwe T. , Kourist Robert
Published: April 2020

Protein design is limited by the diversity of functional groups provided by the canonical protein „building blocks“. Incorporating noncanonical amino acids (ncAAs) into enzymes enables a dramatic expansion of their catalytic features. For this, quick identification of fully translated and correctly folded variants is decisive. Herein, we report the engineering of the enantioselectivity of an esterase utilizing several ncAAs. Key for the identification of active and soluble protein variants was the use of the split‐GFP method, which is crucial as it allows simple determination of the expression levels of enzyme variants with ncAA incorporations by fluorescence. Several identified variants led to improved enantioselectivity or even inverted enantiopreference in the kinetic resolution of ethyl 3‐phenylbutyrate.
Inferring kinetic dissolution of NaCl in aqueous glycol solution using a low‐cost apparatus and population balance model
Authors: Curitiba Marcellos Caio Felippe , Senna Figueiredo Camila M. , Tavares Frederico W. , de Souza Maurício Bezerra , da Cunha Lage Paulo Laranjeira , da Silva João Francisco Cajaiba , Secchi Argimiro R. , Barreto Amaro G.
Published: April 2020

An experimental methodology for inferring brine dissolution rate in monoethylene glycol (MEG) solutions at different temperatures using a webcam combined with a mathematical model is presented. The measurement system is designed to track the RGB (red, green, and blue) colour variations during the dissolution process. A dynamic model augmented with the population balance equation is applied to describe the dissolution process. Moreover, the dissolution rate is consistently related to the temperature and MEG concentration through the driving force based on the Gibbs energy and chemical affinity. The applied low‐cost measurement apparatus proved to be a useful resource for tracking the dissolution dynamics in a wide range of undersaturation.
A medical image segmentation method based on hybrid active contour model with global and local features
Authors: Li Yuanmu , Wang Zhanqing
Published: April 2020

In this article, we proposed an improved region‐based active contour model based on curve evolution theory and variational level set method. Our method can be used to segment image with intensity inhomogeneity, such as medical computed tomography images. Our model contains a local intensity fitting term that makes the evolution curve stop at boundaries of the object and a global expansion term that makes the evolution curve have the chance to get to every location in the image. Therefore, our model has a good performance to solve the problem of flexible initialization, which exposed in region‐scalable fitting energy model. For the curvature term that occurs during the calculation, we calculated it with a more efficiency and accuracy method. Compared with other models, our model shows good segmentation result and less computation expense. Finally, we will present some experimental results, especially the result of contrast experiment.
Identification of the Irreversible Redox Behavior of Highly Fluorescent Benzothiadiazoles
Authors: Rietsch Philipp , Sobottka Sebastian , Hoffmann Katrin , Hildebrandt Pascal , Sarkar Biprajit , Resch‐Genger Ute , Eigler Siegfried
Published: April 2020

Redox switches are applied in various fields of research, including molecular lifts, electronic devices and sensors. Switching the absorbance between UV and Vis/NIR by redox processes is of interest for applications in light harvesting or biomedicine. Here, we present a series of push‐pull benzothiadiazole derivatives with high fluorescence quantum yields in solution and in the crystalline solid state. Spectroelectrochemical analysis reveals the switching of UV‐absorption in the neutral state to Vis/NIR absorption in the reduced state. We identify the partial irreversibility of the switching process, which appears to be reversible on the cyclic voltammetry timescale.
Pulmonary small cell carcinoma: Review, common and uncommon differentials, genomics and management
Authors: Sung Simon , Shirazi Maryam , Shu Catherine A. , Crapanzano John P. , Saqi Anjali
Published: April 2020

Lung cancer is the leading cause of cancer‐related death worldwide. It is divided into sub‐categories based upon morphology, immunostaining pattern, biology, molecular profile, and/or treatment options. Up until the early 2000s when driver mutations with targeted therapies were identified in a subset of adenocarcinomas, the most critical distinction of lung carcinomas was driven by differences in treatment between small cell carcinoma (SCC) and nonsmall cell lung carcinoma (NSCLC). The distinction between SCC and NSCLC remains critical in the 21st century for management, especially for advanced stage cancer. In the vast majority of cases, morphological features are sufficient to separate SCC from other types of lung cancers. In some instances, however, cytomorphological features and immunohistochemical overlap with other tumors, limited sample availability, and/or crush artifact pose diagnostic challenges. The aim of this review is to highlight salient features of SCC and ancillary studies to distinguish it from common and uncommon potential mimickers, as well as provide updates in genomics and management.
An African bat in Europe, Plecotus gaisleri: Biogeographic and ecological insights from molecular taxonomy and Species Distribution Models
Authors: Ancillotto Leonardo , Bosso Luciano , Smeraldo Sonia , Mori Emiliano , Mazza Giuseppe , Herkt Matthias , Galimberti Andrea , Ramazzotti Fausto , Russo Danilo
Published: April 2020

Because of the high risk of going unnoticed, cryptic species represent a major challenge to biodiversity assessments, and this is particularly true for taxa that include many such species, for example, bats. Long‐eared bats from the genus Plecotus comprise numerous cryptic species occurring in the Mediterranean Region and present complex phylogenetic relationships and often unclear distributions, particularly at the edge of their known ranges and on islands. Here, we combine Species Distribution Models (SDMs), field surveys and molecular analyses to shed light on the presence of a cryptic long‐eared bat species from North Africa, Plecotus gaisleri, on the islands of the Sicily Channel, providing strong evidence that this species also occurs in Europe, at least on the islands of the Western Mediterranean Sea that act as a crossroad between the Old Continent and Africa. Species Distribution Models built using African records of P. gaisleri and projected to the Sicily Channel Islands showed that all these islands are potentially suitable for the species. Molecular identification of Plecotus captured on Pantelleria, and recent data from Malta and Gozo, confirmed the species' presence on two of the islands in question. Besides confirming that P. gaisleri occurs on Pantelleria, haplotype network reconstructions highlighted moderate structuring between insular and continental populations of this species. Our results remark the role of Italy as a bat diversity hotspot in the Mediterranean and also highlight the need to include P. gaisleri in European faunal checklists and conservation directives, confirming the usefulness of combining different approaches to explore the presence of cryptic species outside their known ranges—a fundamental step to informing conservation.
Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE)
Authors: Tanaka Atsushi , Hisauchi Itaru , Taguchi Isao , Sezai Akira , Toyoda Shigeru , Tomiyama Hirofumi , Sata Masataka , Ueda Shinichiro , Oyama Jun‐ichi , Kitakaze Masafumi , Murohara Toyoaki , Node Koichi ,   CANDLE Trial Investigators
Published: April 2020

Aims

Little is known about the impact of sodium glucose co‐transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on changes in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), in that patient population.

Methods and results

Patients with T2D and stable CHF, randomized to receive canagliflozin 100 mg or glimepiride (starting‐dose: 0.5 mg), were examined using the primary endpoint of non‐inferiority of canagliflozin vs. glimepiride, defined as a margin of 1.1 in the upper limit of the two‐sided 95% confidence interval (CI) for the group ratio of percentage change in NT‐proBNP at 24 weeks. Data analysis of 233 patients showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6 ± 14.6%, with 71% of patients having a preserved LVEF (≥50%). Ratio of NT‐proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P = 0.226) and therefore did not meet the prespecified non‐inferiority margin. However, NT‐proBNP levels did show a non‐significant trend lower in the canagliflozin group [adjusted group difference; −74.7 pg/mL (95% CI, −159.3 to 10.9), P = 0.087] and also in the subgroup with preserved LVEF [−58.3 (95% CI, −127.6 to 11.0, P = 0.098]).

Conclusions

This study did not meet the predefined primary endpoint of changes in NT‐proBNP levels, with 24 weeks of treatment with canagliflozin vs. glimepiride. Further research is warranted to determine whether patients with heart failure with preserved ejection fraction, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors.
Nurse shark T‐cell receptors employ somatic hypermutation preferentially to alter alpha/delta variable segments associated with alpha constant region
Authors: Ott Jeannine A. , Harrison Jenna , Flajnik Martin F. , Criscitiello Michael F.
Published: April 2020

In addition to canonical TCR and BCR, cartilaginous fish assemble noncanonical TCR that employ various B‐cell components. For example, shark T cells associate alpha (TCR‐α) or delta (TCR‐δ) constant (C) regions with Ig heavy chain (H) variable (V) segments or TCR‐associated Ig‐like V (TAILV) segments to form chimeric IgV‐TCR, and combine TCRδC with both Ig‐like and TCR‐like V segments to form the doubly rearranging NAR‐TCR. Activation‐induced (cytidine) deaminase‐catalyzed somatic hypermutation (SHM), typically used for B‐cell affinity maturation, also is used by TCR‐α during selection in the shark thymus presumably to salvage failing receptors. Here, we found that the use of SHM by nurse shark TCR varies depending on the particular V segment or C region used. First, SHM significantly alters alpha/delta V (TCRαδV) segments using TCR αC but not δC. Second, mutation to IgHV segments associated with TCR δC was reduced compared to mutation to TCR αδV associated with TCR αC. Mutation was present but limited in V segments of all other TCR chains including NAR‐TCR. Unexpectedly, we found preferential rearrangement of the noncanonical IgHV‐TCRδC over canonical TCR αδV‐TCRδC receptors. The differential use of SHM may reveal how activation‐induced (cytidine) deaminase targets V regions.
Imidazolyl Alanes – Synthesis, Structures, and Reactivity Studies
Authors: Simon Martin , Radius Michael , Wagner Hanna E. , Breher Frank
Published: April 2020

Targeting the synthesis of Al/C based ambiphilic molecules, we investigated the dehydrohalogenation of a series of (benz)imidazole alane adducts. Depending on the steric bulk of the heterocycle, different dimeric products with various ring sizes were obtained. Dehydrohalogenation of the adduct of 1‐mesityl imidazole (MesIm) and 0.5 [tBu2AlBr]2 furnished the dimer 2, featuring a “classical” N‐heterocyclic carbene (NHC) and a mesoionic or “abnormal” NHC (aNHC) subunit within a single molecule. The dimer is bound loosely enough to allow thermally induced isomerization of 2 into the isomers 2NHC (all NHC) and 2aNHC (all aNHC). Dehydrohalogenation of the adduct of 1‐mesityl‐2‐methyl imidazole (MesImMe) and 0.5 [tBu2AlBr]2 (4) yielded the dimeric compound 5 consisting of two N‐heterocyclic olefin (NHO) subunits. Although these six‐ and eight‐membered heterocycles show no FLP‐type reactivity towards small molecules like H2, CO or CO2, we observed an ambiphilic behavior of the imidazolyl alanes during our studies. Salt metathesis reactions using MesIm resulted in the formation of 3, which can be viewed as tBu2AlBr adduct of an Al/N ambiphile. Utilizing heterocycles such as benzimidazole or spiroindole provided the entry point to C–H (7, 9) and N–H (10) activation products, most likely resulting from a reactivity of intermediate species as Al/C ambiphiles.
1,4‐Diethynylbenzene‐Bridged [Cp*(dppe)Fe]n+ Units: Effect of 2,5‐Ethynyl Groups on the Chemical and Electronic Properties
Authors: Makhoul Rim , Groizard Thomas , Hamon Paul , Roisnel Thierry , Dorcet Vincent , Kahlal Samia , Halet Jean‐François , Hamon Jean‐René , Lapinte Claude
Published: April 2020

The bis(ironvinylidene) complex [1,4‐{Cp*(dppe)Fe=C=CH}2‐2,5‐(C≡CH)2‐C6H2](PF6)2 ([2–2H](PF6)2) was prepared from 1,2,4,5‐tetraethynylbenzene and two equiv. of Cp*(dppe)FeCl in 87 % yield. The reaction is very selective and [2–2H](PF6)2 is the unique organoiron species to be formed. Deprotonation of [2–2H](PF6)2 provided the target complex 2 (66 % yield) and subsequent oxidation gave the monocationic and dicationic complexes 2(PF6) and 2(PF6)2. The new complexes were characterized by ESI‐mass spectrometry, IR, multinuclear NMR, ESR and Mössbauer spectroscopy, and XRD analyses on single crystals for [2–2H](PF6)2 and 2(PF6)2. The magnetic properties of 2(PF6)2 were investigated by VT 1H NMR. The data were analyzed with the support of quantum chemistry calculations. The terminal ethynyl groups on the aromatic ring of the bridge modify the population of the bridge‐oxidized state, weaken the electronic communication (Hab ≈ 601 cm–1) and strengthen magnetic coupling interactions (J = –530 cm–1) compared to the unsubstituted species (Hab = 1700 cm–1 and J = –340 cm–1, respectively).
An Interlaboratory Study on the Stability of All‐Printable Hole Transport Material–Free Perovskite Solar Cells
Authors: De Rossi Francesca , Barbé Jérémy , Tanenbaum David M. , Cinà Lucio , Castriotta Luigi Angelo , Stoichkov Vasil , Wei Zhengfei , Tsoi Wing Chung , Kettle Jeffrey , Sadula Artem , Chircop John , Azzopardi Brian , Xie Haibing , Di Carlo Aldo , Lira-Cantú Monica , Katz Eugene A. , Watson Trystan M. , Brunetti Francesca
Published: April 2020

Comparisons between different laboratories on long‐term stability analyses of perovskite solar cells (PSCs) is still lacking in the literature. This work presents the results of an interlaboratory study conducted between five laboratories from four countries. Carbon‐based PSCs are prepared by screen printing, encapsulated, and sent to different laboratories across Europe to assess their stability by the application of three ISOS aging protocols: (a) in the dark (ISOS‐D), (b) under simulated sunlight (ISOS‐L), and (c) outdoors (ISOS‐O). Over 1000 h stability is reported for devices in the dark, both at room temperature and at 65 °C. Under continuous illumination at open circuit, cells survive only for few hours, although they recover after being stored in the dark. Better stability is observed for cells biased at maximum power point under illumination. Finally, devices operate in outdoors for 30 days, with minor degradation, in two different locations (Barcelona, Spain and Paola, Malta). The findings demonstrate that open‐circuit conditions are too severe for stability assessment and that the diurnal variation of the photovoltaic parameters reveals performance to be strongly limited by the fill factor, in the central hours of the day, due to the high series resistance of the carbon electrode.
Health workers' safety during tracheostomy in COVID‐19 patients: Homemade protective screen
Authors: Cordier Pierre‐Yves , De La Villeon Bruno , Martin Edouard , Goudard Yvain , Haen Pierre
Published: April 2020

As an aerosol and droplets generating procedure, tracheostomy increases contamination risks for health workers in the coronavirus disease context. To preserve the health care system capacity and to limit virus cross‐transmission, protecting caregivers against coronavirus infection is of critical importance. We report the use of external fixator equipment to set up a physical interface between the patient's neck and the caregiver performing a tracheostomy in COVID‐19 patients. Once the metal frame set in place, it is wrapped with a single‐use clear and sterile cover for surgical C‐arm. This installation is simple, easy, and fast to achieve and can be carried out with inexpensive material available in every hospital. This physical interface is an additional safety measure that prevents the direct projection of secretions or droplets. It should, of course, only be considered as a complement to strict compliance with barrier precautions and personal protective equipment.
AI‐assisted data dissemination methods for supporting intelligent transportation systems†
Authors: Sun Peng , Boukerche Azzedine
Published: April 2020

As an essential component of Smart Cities, the intelligent transportation system (ITS) utilizes a large number of deployed traffic monitoring equipment and Internet‐of‐Vehicles technologies to timely transfer traffic management measures formulated based on accurately grasped real‐time traffic conditions to all transportation system participants for improving the operating efficiency and safety of the transportation system. The key to achieving this advantage is effective data transmission. Correspondingly, by exploiting these recorded massive traffic data, a variety of AI‐assisted data transmission methods are designed to improve the data transmission performance in the vehicular network environment (VNE) to ensure the effective operation of ITS. To help readers get an initial understanding of how AI technology can help with data transmission in VNE, in this letter, we will discuss two types of AI‐assisting methods targeting the data dissemination performance enhancement in vehicle‐to‐vehicle (V2V) and vehicle‐to‐infrastructure (V2I) communications respectively in detail, that is, predictive handover/pre‐caching algorithm and predicted traffic flow‐assisted data routing protocols. Additionally, empirical evaluation is conducted to demonstrate the effectiveness of the discussed methods.
Subchronic (90‐day) toxicity assessment of Somacy‐FP100, a lipopolysaccharide‐containing fermented wheat flour extract from Pantoea agglomerans
Authors: Phipps Kirt R. , Sulaiman Christina , Simon Ryan , Holalagoudar Shivakumar , Kohchi Chie , Nakata Yoko
Published: April 2020

Pantoea agglomerans is a Gram‐negative bacterium that is ubiquitous in the environment, colonizing animals, humans, and numerous plants, including cotton and wheat. A lipopolysaccharide‐containing fermented wheat flour extract from P. agglomerans (Somacy‐FP100) is proposed for use as a food ingredient for individuals seeking foods for healthy aging. Previously published genotoxicity studies with Somacy‐FP100 reported its lack of genotoxicity in vitro, but a subchronic toxicity study has not yet been performed. Therefore, to demonstrate the safety of Somacy‐FP100 for use as a food ingredient, a 90‐day oral (gavage) toxicity study in rats was conducted. Male and female Han Wistar rats were administered vehicle (control) or Somacy‐FP100 at 500, 1500, or 4500 mg/kg body weight/day at a dose volume of 10 mL/kg body weight, for at least 90 days. No test article‐related adverse clinical signs or effects on body weight, food consumption, or clinical pathology were observed, and there were no macroscopic or microscopic findings related to the test article. Therefore, 4500 mg/kg body weight/day (the highest dose tested and highest feasible dose) was established as the no‐observed‐adverse‐effect level. This absence of subchronic toxicity, in addition to the previously reported lack of genotoxicity, demonstrates the safety of Somacy‐FP100 for use as a food ingredient.
Structural binding perspectives of a major tobacco alkaloid, nicotine, and its metabolite cotinine with sex‐steroid nuclear receptors
Authors: Rehan Mohd , Ahmad Ejaz , Beg Mohd A.
Published: April 2020

Globally, more than a billion people smoke tobacco making it one of the biggest public health problems and a leading risk factor for global deaths. Nicotine, the main alkaloid in tobacco, has been shown to be associated with fertility problems in men and women. The adverse effects of tobacco/nicotine on reproduction have been attributed to deleterious effects on gametes, steroidogenic imbalance, and competitive inhibition of steroid receptors. The present study reports the sex‐steroid receptor disrupting potential of nicotine and its major metabolite cotinine against the estrogen receptor‐α (ERα), ERβ, androgen receptor (AR), and progesterone receptor (PR). Both ligands bound in the ligand‐binding pockets of ERα, ERβ, AR and PR and formed important hydrophobic interactions with different amino‐acid residues of receptors. Most of the residues of ERα, ERβ, AR and PR interacting with nicotine and cotinine were common with those of native/bound ligands of the receptors. Interacting amino acids most important for binding of nicotine and cotinine with each receptor were identified by loss in accessible surface area. Amino acids Leucine‐346, Leucine‐384 and Phenylalanine‐404 for ERα; Methionine‐336, Phenylalanine‐356 and Leucine‐298 for ERβ; and Leucine‐704 and Leucine‐718, respectively for AR and PR, were the most important residues for binding with nicotine and cotinine. Among the four receptors, based on the number of interactions, nicotine and cotinine had greater potential to interfere in the signaling of ERβ. In conclusion, the results suggested that nicotine and cotinine bind and interact with sex‐steroid nuclear receptors and have potential to interfere in the steroid hormone signaling resulting in reproductive dysfunction.
Spectroscopic studies, Density Functional Theory calculations, and non‐linear optical properties of binuclear Fe(III), Co(II), Ni(II), Cu(II), and Zn(II) complexes of OONN Schiff base ligand
Authors: Moustafa Hussein , Mohamed Gehad G. , Elramly Salwa
Published: April 2020

The binuclear complexes of Fe(III), Co(II), Ni(II), Cu(II), and Zn(II) with 2‐[3‐(benzylideneamino)‐2‐(benzylidenehydrazono)‐4‐oxothiazolidin‐5‐yl] acetic acid ligand (HL) were prepared and their stoichiometry was determined by elemental analysis. The stereochemistry of the studied binuclear metal complexes was confirmed by analyzing their infrared spectra, 1H NMR, and magnetic moment. Thermal decomposition studies of the binuclear complexes have been performed to demonstrate the status of water molecules present in these binuclear complexes and their general decomposition pattern. The equilibrium geometry of the ligand and its studied complexes were calculated using density function theory (DFT) calculations at the B3LYP/GENECP level of the theory. The results show that the ligand and its complexes are nonplanar structures as indicated from the values of the dihedral angles. Extent of distortion from regular geometry has been performed and discussed in terms of the values of the angles between the central metals and the coordinated sites. The EHOMO and ELUMO energies of the studied ligand and its complexes are used to calculate the global properties. The nonlinear optical parameters (NLO), anisotropy of the polarizibility (Δα), and the mean first‐order hyperpolarizability (<β>) were calculated. The (<β>) values were compared with Urea as a reference molecule and the results of (<β>) values showed that the ligand and the studied complexes have good NLO behaviors.
Downregulation of XIST ameliorates acute kidney injury by sponging miR‐142‐5p and targeting PDCD4
Authors: Tang Bo , Li Weiliang , Ji Tingting , Li Xiaoying , Qu Xiaolei , Feng Linhong , Zhu Yingchun , Qi Yinghui , Zhu Chun , Bai Shoujun
Published: April 2020

Acute kidney injury (AKI) is a common kidney disease that markedly affects public health. To date, the roles of long noncoding RNA XIST in AKI are poorly understood. Here, we investigated the biological functions of XIST in AKI. We observed that XIST expression increased in patients with AKI and HK‐2 cells stimulated by CoCl2. In addition, a rat AKI model induced by ischemia–reperfusion was established. Tumor necrosis factor‐α, interleukin‐6, and cyclooxygenase‐2 messenger RNA expression were induced in vivo; moreover, XIST expression was upregulated. Knockdown of XIST significantly repressed CoCl2‐triggered injury in HK‐2 cells. However, microRNA (miR)‐142‐5p, a downstream target of XIST, was downregulated in AKI. miR‐142‐5p was repressed by XIST and miR‐142‐5p could inhibit CoCl2‐induced injury in HK‐2 cells. Moreover, PDCD4 expression was significantly increased in AKI. PDCD4 was predicted to be the target of miR‐142‐5p. Subsequently, loss of PDCD4 was able to retard injury in HK‐2 cells exposed to CoCl2. Thus, we suggest that XIST regulates miR‐142‐5p and PDCD4, and it has the potential to function as a biomarker in therapeutic strategies for AKI.
Overexpression of miR‐181a‐5p inhibits retinal neovascularization through endocan and the ERK1/2 signaling pathway
Authors: Chen Xiuping , Yao Yiyun , Yuan Fei , Xie Bing
Published: April 2020

Retinal neovascularization (RNV) is a common pathological feature of angiogenesis‐related retinopathy. Endocan inhibition has previously been reported to suppress RNV in oxygen‐induced retinopathy (OIR); however, its molecular mechanisms remain to be elucidated. Here, we investigated the role and mechanism of endocan in OIR. We established an OIR mouse model and detected aberrant endocan overexpression in OIR mouse retinas. Endocan inhibition through small interfering RNA or a neutralizing antibody inhibited vascular endothelial growth factor‐induced cell survival, cell proliferation, and tube formation in human retinal endothelial cells in vitro and reduced the RNV area in vivo. Using RNA sequencing, a luciferase reporter assay, and bioinformatics analyses, we identified endocan as a microRNA‐181a‐5p target gene. The antiangiogenic effect of miR‐181a‐5p on RNV was verified by intravitreal injection, and we showed that this involved the extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) signaling pathway. Collectively, our data demonstrate that miR‐181a‐5p/endocan regulates retinal angiogenesis through the ERK1/2 signaling pathway and might represent an attractive therapeutic strategy for RNV.
A new perspective on the static metabolic allometry of carabid beetles
Authors: Packard Gary C.
Published: April 2020

The conventional allometric method entails fitting a straight line to logarithmic transformations of the original bivariate data and then back‐transforming the resulting equation (at least implicitly) to form a two‐parameter power function, Y = a × Xb, on the arithmetic scale. Although the protocol is widely used in contemporary research, it commonly performs poorly and thereby leads investigators to form inaccurate impressions of the dominant pattern in their data. Here I re‐examine the metabolic allometry for six species of carabid beetle to illustrate the problem that arises when pattern in the original data can be described by two (or more) statistically equivalent equations with different functional form. Whereas conventional analyses of data for the beetles yielded only a single descriptive model for each dataset (i.e., the two‐parameter power equation), the more versatile protocol used here fitted two to four statistically equivalent equations (including the two‐parameter power function) to the same sets of observations. Conclusions based on just the power equation estimated by conventional allometry would be misleading because the equation does not afford a unique description for pattern in the data.