bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Biocatalytic Activity of the Debaryomyces Species in Seawater
Authors: Andreu Cecilia , del Olmo Marcel⋅lí
Published: May 2019

Biocatalysis is an environmentally friendly strategy widely used in the chemical and pharmaceutical industries. One of its approaches consists in utilizing whole cells, which usually involves the consumption of large quantities of water. Oceans cover a large part of the Earth's surface, and constitute an important reservoir that can be used as an alternative to freshwater in chemical reactors. This work analyzed the behavior of several yeast halotolerant species belonging to genera Debaryomyces and Schwanniomyces in both freshwater and seawater. It concluded that these microorganisms were more resistant to organic solvents/compounds in the second medium. Their metabolic activity was also greater, which made the reduction reaction of several prochiral ketones more effective. Besides, yeasts cells displayed better performance in subsequent recycling steps, which could help reduce the costs of the process.
Evidence of Mixed‐Ligand Complexes in Cu−CHA by Reaction of Cu Nitrates with NO/NH3 at Low Temperature
Authors: Negri Chiara , Borfecchia Elisa , Cutini Michele , Lomachenko Kirill A. , Janssens Ton V. W. , Berlier Gloria , Bordiga Silvia
Published: May 2019

The reactivity with a NO/NH3 mixture of Cu‐nitrate complexes formed on the surface of a Cu−CHA catalyst active in the Selective Catalytic Reduction of NOx with NH3 (NH3−SCR) was followed at 50 °C by in situ spectroscopic techniques. The catalyst (Si/Al=15; Cu/Al=0.5) was first exposed to NO/O2 (mimicking the SCR oxidative half‐cycle), mainly resulting in the formation of chelating bidentate framework‐interacting CuII‐nitrates. These intermediates were gradually detached from the framework in the presence of NO/NH3 (or NH3 alone), forming mixed‐ligand mobile [CuII(NH3)3(NO3)]+ complexes, with infrared bands at 1624 (δNH3), 1430 and 1325 cm−1 (monodentate nitrate νNO2asym and νNO2sym, respectively). X‐ray absorption and Diffuse Reflectance UV‐Vis spectroscopies showed that during this transformation the CuII/CuI reduction, observed under similar conditions at 200 °C, hardly occurred. DFT calculations confirmed the stability of nitrate ligands in the monodentate conformation in [CuII(NH3)3(NO3)]+ complexes when solvated by ammonia. The resulting structure was successfully used to fit the corresponding experimental EXAFS spectra. The gradual change of ligands in the CuII coordination sphere was confirmed by the blue shifts of both
and Ligand to Metal Charge Transfer bands in Diffuse Reflectance UV‐Vis spectra, with formation of features (27500, 32000 and 38000 cm−1) ascribable to the mixed‐ligand configuration.
A Simple and Efficient Procedure for Rh(I)‐ and Ir(I)‐complex Catalyzed Para‐hydrogenation of Alkynes and Alkenes in Aqueous Media Resulting in Strong PHIP Effects
Authors: Papp Gábor , Horváth Henrietta , Joó Ferenc
Published: May 2019

Catalytic hydrogenations with para‐H2 may lead to strong para‐hydrogen induced polarization (PHIP) and the hyperpolarized probe molecules may enable the application of the Magnetic Resonance Imaging (MRI) diagnostic modality for metabolism imaging. The use of water as a solvent for para‐hydrogenation reactions is very challenging due to the fast exchange between the catalytically active metal hydrides and the water protons and also because of the low hydrogen solubility in water. Here we report that several water‐soluble Rh(I)‐ and Ir(I)‐complexes with N‐heterocyclic carbene (NHC) and/or tertiary phosphine ligands efficiently catalyze the synthesis of hyperpolarized compounds by para‐hydrogenation in aqueous media.
Al/P‐ and Ga/P‐Based Frustrated Lewis Pairs and Electronically Unsaturated Substrates: Ring Cleavage and Ring Closure, C−C and C−N Bond Formation
Authors: Pleschka Damian , Uebing Marten , Lange Merten , Hepp Alexander , Wübker Anna‐Lena , Hansen Michael Ryan , Würthwein Ernst‐Ulrich , Uhl Werner
Published: May 2019

Al/P‐ and Ga/P‐based frustrated Lewis pairs (FLPs) reacted with an azirine under mild conditions under cleavage of the heterocycle on two different positions. Opening of the C−C bond yielded an unusual nitrile–ylide adduct in which a C−N moiety coordinated to the FLP backbone. Cleavage of a C−N bond afforded the thermodynamically favored enamine adduct with the N atom bound to P and Al or Ga atoms. Ring closure was observed upon treatment of an Al/P FLP with electronically unsaturated substrates (4‐(1‐cyclohexenyl)‐1‐aza‐but‐1‐en‐3‐ynes) and yielded by C−N bond formation hexahydroquinoline derivatives, which coordinated to the FLP through P−C and Al−C bonds. Diphenylcyclopropenone showed a diverse reactivity, which depending on steric shielding and the polarizing effect of Al or Ga atoms afforded different products. An AltBu2/P FLP yielded an adduct with the C=O group coordinated to P and Al. The dineopentyl derivative gave an equilibrium mixture consisting of a similar product and a simple adduct with O bound to Al and a three‐coordinate P atom. Both compounds co‐crystallize. The Ga/P FLP only formed the simple adduct with the same substrate. Rearrangement resulted in all cases in C3‐ring cleavage and migration of a mesityl group from P to a former ring C atom by C−C bond formation. Diphenylthiocyclopropenone (evidence for the presence of P=C bonds) and an imine derivative afforded similar products.
Unveiling the Mechanisms of Aquaglyceroporin‐3 Water and Glycerol Permeation by Metadynamics
Authors: Wragg Darren , de Almeida Andreia , Casini Angela , Leoni Stefano
Published: May 2019

Water and glycerol permeation through human AQP3 are described by exploiting advanced metadynamics approaches, which enabled both to explore the free energies involved in pore permeation and to achieve a description of the mechanisms with an atomistic level of detail.
Streamlined Synthesis of Diaminopyridines by Pd‐Catalyzed Ammonia Coupling with Deactivated Amino‐Chloropyridines
Authors: Bourriquen Florian , Bruneau‐Voisine Antoine , Jeandin Aliénor , Stihle Etienne , Fantasia Serena
Published: May 2019

An efficient and cost‐effective two‐step synthesis of diaminopyridines, fundamental building blocks of biologically active compounds, is reported. The advantages over previously reported routes include cost and wider availability of the bromo‐chloropyridine starting materials and the straightforward accessibility to an extended array of diaminopyridine regioisomers. The key enabler of this synthetic strategy is the development of an unprecedented palladium‐catalyzed coupling reaction of ammonia with chloropyridines deactivated by the presence of an alkylamino substituent. The coupling reaction was accomplished with very low catalyst loadings under remarkably mild reaction conditions, making the system particularly suitable for both academic and industrial applications. The utility of this methodology is exemplified by the application to the synthesis of highly relevant scaffolds, including the synthetic intermediates of the marketed drugs Ribociclib and Palbociclib.
Genotype Imputation in Genome‐Wide Association Studies
Authors: Naj Adam C.
Published: May 2019

Genotype imputation infers missing genotypes in silico using haplotype information from reference samples with genotypes from denser genotyping arrays or sequencing. This approach can confer a number of improvements on genome‐wide association studies: it can improve statistical power to detect associations by reducing the number of missing genotypes; it can simplify data harmonization for meta‐analyses by improving overlap of genomic variants between differently‐genotyped sample sets; and it can increase the overall number and density of genomic variants available for association testing. This article reviews the general concepts behind imputation, describes imputation approaches and methods for various types of genotype data, including family‐based data, and identifies web‐based resources that can be used in different steps of the imputation process. For practical application, it provides a step‐by‐step guide to implementation of a two‐step imputation process consisting of phasing of the study genotypes and the imputation of reference panel genotypes into the study haplotypes. In addition, this review describes recently developed haplotype reference panel resources and online imputation servers that are capable of remotely and securely implementing an imputation workflow on uploaded genotype array data. © 2019 by John Wiley & Sons, Inc.
Enantioselective Photochromism under Circularly Polarized Light
Authors: Hashim P. K , Tamaoki Nobuyuki
Published: May 2019

The introduction of asymmetry into molecular systems by external chiral stimuli greatly contributes to our understanding of the intriguing homochirality which exists in biomolecules. Circularly polarized light (CPL) is a well‐known chiral physical force (right‐ or left‐handed), which can influence the enantiomeric equilibrium of racemic chiral compounds via preferential interaction with one of the enantiomers. As a light absorption moiety in the chiral system, photochromic molecules best contribute to the enhancement of spectral characteristics, which is highly desirable for the experimental observation of CPL‐based enantioselective reactions. In this Minireview, CPL‐directed enantioselective photochromism, with an emphasis on several azobenzene derivatives, will be discussed. We briefly discuss the recent examples of chiral amplification methods that utilize CPL chiral forces along with a short perspective for future directions.
Mesityl or Imide Acridinium Photocatalysts: Accessible Versus Inaccessible Charge‐Transfer States in Photoredox Catalysis
Authors: Gini Andrea , Rigotti Thomas , Pérez‐Ruiz Raúl , Uygur Mustafa , Mas‐Ballesté Rubén , Corral Inés , Martínez‐Fernández Lara , de la Peña O'Shea Victor A. , García Mancheño Olga , Alemán José
Published: May 2019

A study on C9‐imide acridinium photocatalysts with enhanced photoredox catalytic activity with respect to the well‐established C9‐mesityl acridinium salt is presented. The differences observed rely on the diverse accessibility of singlet charge‐transfer excited states, which have been proven by CASPT2/CASSCF calculations, fluorescence and quenching studies.
Lignin for Nano‐ and Microscaled Carrier Systems: Applications, Trends, and Challenges
Authors: Sipponen Mika Henrikki , Lange Heiko , Crestini Claudia , Henn Alexander , Österberg Monika
Published: May 2019

Invited for this month′s cover is the Review by Mika H. Sipponen and collaborators at Aalto University (Finland), University of Naples Federico II (Italy), and University of Venice Ca’ Foscari (Italy). The image shows the versatility of lignins in the fabrication of carrier materials for various active ingredients in nanomedicine, agricultural chemistry, and biocatalysis. The Review itself is available at 10.1002/cssc.201900480.
Relapse prevention and selective serotonin reuptake inhibitor medication in two adolescents with anorexia nervosa
Authors: Luzier Jessica , Rached Kristina , Talley Jessica
Published: May 2019

Objective

Clinicians and researchers have long struggled to find effective treatments for people with anorexia nervosa (AN). Although most clinical guidance suggests that selective‐serotonin reuptake inhibitor (SSRI) medication is not an effective first‐line treatment for AN, in practice, these medicines continue to be frequently prescribed for comorbid diagnoses.

Method

In this case report, two adolescents who were in sustained remission from AN either relapsed or began to decline significantly once their dose of SSRI medication was tapered.

Results

In Case A, despite a very slow and measured taper, this child dropped significant weight in a short amount of time after the medication was discontinued. Fortunately for Case B, symptoms emerged before the taper was complete, and providers could quickly increase the dose of medication early in her struggle with AN thoughts and urges.

Discussion

A brief review of literature regarding SSRI medication use in AN is presented along with considerations for future research.
PdII/Novel Chiral Cinchona Alkaloid Oxazoline‐Catalyzed Enantioselective Oxidative Cyclization of Aromatic Alkenyl Amides
Authors: Tian Qinqin , Liu Yulong , Wang Xiaoyun , Wang Xie , He Wei
Published: May 2019

A highly enantioselective PdII‐catalyzed aza‐Wacker oxidation tandem cyclization of aromatic nitrogen‐containing dienes has been achieved in the presence of novel chiral cinchona alkaloid oxazoline ligands for the first time, affording chiral dihydroindole nitrogen‐containing polycyclic compounds with good yields (up to 83 %), high diastereoselectivities (> 95:5 dr), and excellent enantioselectivities (up to 97 % ee).
Some thoughts about enantioseparations in capillary electrophoresis
Authors: Fanali Salvatore , Chankvetadze Bezhan
Published: May 2019

In this overview the goal of the authors was to analyze from the historical perspective the reasons of success and failure of chiral capillary electrophoresis. In addition, the current trends are analyzed, unique advantages of capillary electrophoresis are highlighted and some future directions are discussed.
Manipulating the Composition and Structure of Solid Electrolyte Interphase at Graphite Anode by Adjusting the Formation Condition
Authors: Zhu Taohe , Hu Qiyang , Yan Guochun , Wang Jiexi , Wang Zhixing , Guo Huajun , Li Xinhai , Peng Wenjie
Published: May 2019

The solid electrolyte interphase (SEI) plays an important role in the comprehensive electrochemical performance of lithium‐ion batteries. However, graphite generates a 10% volume expansion during cycles, resulting in structural cracking of the SEI and further electrolyte decomposition. Herein, by adjusting the formation current density, the composition and structure of the SEI are regulated to optimize the electrochemical performance of graphite electrodes. The results manifest that the SEI is mainly formed between 1.1 and 1.4 V, and a lower formation current density is favorable for forming an excellent SEI at the graphite electrode surface. The SEI formed under such condition possesses more organic lithium salts and less inorganic lithium salts, and it is enwrapped onto the surface of the graphite anode more uniformly as compared with higher formation current density. Meanwhile, the derived SEI is more stable and thicker, which can effectively stabilize the interface of the electrode/electrolyte to enhance the cyclic stability of graphite anode materials after the formation step, so as to buffer its volume change during the cycles.
Design and analysis of fuel cell and photovoltaic based 110 V DC microgrid using hydrogen energy storage
Authors: Alam Mohd , Kumar Kuldeep , Dutta Viresh
Published: May 2019

A 110 V DC system has been designed for photovoltaic and fuel cell generators to operate DC loads such as LED lights, fans, laptop, and mobile phone charging in a DC microgrid. As the output characteristics of photovoltaic and fuel cell generators vary according to the operating conditions and connected load, the designing of the DC‐DC converter ensures that a stable DC voltage is available to the load under varying input voltage. A boost converter (with output power of 500 W) has therefore been fabricated to generate a stable 110 V output voltage for a widely varying input voltage (30‐85 V), which utilizes photovoltaic (750 Wp) and a proton exchange membrane fuel cell (1 kW) power generators. The DC‐DC converter is designed to use either a silicon or silicon carbide power MOSFET by a suitably modified circuit, both are operated at 20 kHz switching frequency. The maximum converter efficiencies with silicon and silicon carbide MOSFETs are 95.7% and 97.8%, respectively. It is shown that the DC‐DC converter provides a stable operation with variations in operating conditions of photovoltaic and fuel cell generators and is well suited for application in a 110 V DC microgrid and Railways load applications. A feasibility study is performed for determining the sizes of photovoltaic and fuel cell generators to meet the Railways carriage load demand and found to be 5 kW photovoltaic and 5 kW fuel cell.
A probabilistic atlas of the human motion complex built from large‐scale functional localizer data
Authors: Huang Taicheng , Chen Xiayu , Jiang Jian , Zhen Zonglei , Liu Jia
Published: May 2019

Accurate motion perception is critical to dealing with the changing dynamics of our visual world. A cluster known as the human MT+ complex (hMT+) has been identified as a core region involved in motion perception. Several atlases defined based on cytoarchitecture, retinotopy, connectivity, and multimodal features include homologs of the hMT+. However, an hMT+ atlas defined directly based on this region's response for motion is still lacking. Here, we identified the hMT+ based on motion responses from functional magnetic resonance imaging (fMRI) localizer data in 509 participants and then built a probabilistic atlas of the hMT+. As a result, four main findings were revealed. First, the hMT+ showed large interindividual variability across participants. Second, the atlases stabilized when the number of participants used to build the atlas was more than 100. Third, the functional hMT+ showed good agreement with the hMT+ atlases built based on cytoarchitecture, retinotopy, and connectivity, suggesting a good structural–functional correspondence. Fourth, tests on multiple fMRI data sets acquired from independent participants, imaging parameters and paradigms revealed that the functional hMT+ showed higher sensitivity than all other atlases in ROI analysis except that connectivity and multimodal hMT+ atlases in the left hemisphere could infrequently attain comparable sensitivity to the functional atlas. Taken together, our findings reveal the benefit of using large‐scale functional localizer data to build a reliable and representative hMT+ atlas. Our atlas is freely available for download; it can be used to localize the hMT+ in individual participants when functional localizer data are not available.
The long noncoding RNA TP73‐AS1 promotes tumorigenicity of medulloblastoma cells
Authors: Varon Mor , Levy Tal , Mazor Gal , Ben David Hila , Marciano Ran , Krelin Yakov , Prasad Manu , Elkabets Moshe , Pauck David , Ahmadov Ulvi , Picard Daniel , Qin Nan , Borkhardt Arndt , Reifenberger Guido , Leprivier Gabriel , Remke Marc , Rotblat Barak
Published: May 2019

Medulloblastoma is the most common malignant brain cancer in children. Since previous studies have mainly focused on alterations in the coding genome, our understanding of the contribution of long noncoding RNAs (lncRNAs) to medulloblastoma biology is just emerging. Using patient‐derived data, we show that the promoter of lncRNA TP73‐AS1 is hypomethylated and that the transcript is highly expressed in the SHH subgroup. Furthermore, high expression of TP73‐AS1 is correlated with poor outcome in patients with TP53 wild‐type SHH tumors. Silencing TP73‐AS1 in medulloblastoma tumor cells induced apoptosis, while proliferation and migration were inhibited in culture. In vivo, silencing TP73‐AS1 in medulloblastoma tumor cells resulted in reduced tumor growth, reduced proliferation of tumor cells, increased apoptosis and led to prolonged survival of tumor‐bearing mice. Together, our study suggests that the lncRNA TP73‐AS1 is a prognostic marker and therapeutic target in medulloblastoma tumors and serves as a proof of concept that lncRNAs are important factors in the disease.
Combination of vascularization and cilia formation for three‐dimensional airway tissue engineering
Authors: Kreimendahl Franziska , Ossenbrink Sina , Köpf Marius , Westhofen Martin , Schmitz‐Rode Thomas , Fischer Horst , Jockenhoevel Stefan , Thiebes Anja L.
Published: May 2019

Tissue engineering is a promising approach to treat massive airway dysfunctions such as tracheomalacia or tumors. Currently, there is no adequate solution for patients requiring the resection of more than half of the length of their trachea. In this study, the best conditions for combination of three different cell types from the respiratory airway system were investigated to develop a functional ciliated and pre‐vascularized mucosal substitute in vitro. Primary human fibroblasts were combined with respiratory epithelial cells and endothelial cells. As scaffolds, fibrin gel and agarose‐type I collagen blends were used and cultured with different medium compositions to optimize both vascularization and differentiation of the respiratory epithelium. A mixture of endothelial growth medium and epithelial differentiation medium was shown to optimize both vascularization and epithelial growth and differentiation. After 28 days of co‐culture, significantly increased formation of capillary‐like structures was observed in fibrin gels with more than three times higher structure volumes compared to agarose–collagen gels. After 35 days, epithelial differentiation into a pseudostratified epithelium with typical marker expression was improved on fibrin gels. While cilia formation was shown on both scaffolds, a higher number of ciliated cells and longer cilia were observed on fibrin gels. The data elucidate the important interplay of co‐culture parameters and their impact on vascularization as well as epithelium development and provide a basis for development of functional three‐dimensional airway constructs.
Therapeutic effect of curcumin on acrylamide‐induced apoptosis mediated by MAPK signaling pathway in Leydig cells
Authors: Yildizbayrak Nebahat , Erkan Melike
Published: May 2019

The aim of this study was to investigate the possible therapeutic effects of curcumin (CUR), against acrylamide (AA)‐induced toxic effects on Leydig cells. The AA and CUR‐treated cells were evaluated for cell viability, lipid peroxidation, reactive oxygen species (hydroxyl radical and hydrogen peroxide), antioxidant levels (glutathione peroxidase, glutathione‐S‐transferase, and catalase), apoptosis/necrosis rates and phosphorylation status of mitogen‐activated protein kinases (MAPKs). Leydig cells were exposed to four concentrations of AA (1, 10, 100, 1000 µM) in the presence and absence of CUR (2.5 µM) for 24 hours. According to the present result, AA concentration‐dependently, increased the oxidative stress parameters and suppressed the antioxidant enzyme levels, meanwhile induced apoptosis and activated the phosphorylation of extracellular signal‐regulated kinase, p38, and c‐Jun NH
2‐terminal kinase. Moreover, CUR ameliorated the detrimental effects of AA. Thus, AA‐induced apoptosis through activation of the MAPK signaling pathway and CUR has a protective effect against AA‐induced damage in Leydig cells.
Actin depolymerization disrupts karyosphere capsule integrity but not residual transcription in late oocytes of the grass frog Rana temporaria
Authors: Ilicheva Nadya V. , Pochukalina Galina N. , Podgornaya Olga I.
Published: May 2019

Late diplotene oocytes are characterized by an essential decrease in transcriptional activity. At this time, chromosomes condense and form a compact structure named a karyosphere. The karyosphere of grass frogs Rana temporaria is surrounded by a fibrillar karyosphere capsule (KC). One of the main protein constituents of R. temporaria KC is actin. In this study, we used antibodies against different actin epitopes to trace different forms of actin in the KC. We also investigated the effect of F‐actin depolymerization on the oocyte nuclear structures and transcription of chromatin DNA and rDNA in the amplified nucleoli. It was determined that disruption of actin filaments leads to chromosome shrinkage, nucleoli fusion, and distortion of the KC structure, but does not inhibit residual transcription in both the karyosphere and the nucleoli.
Association of excision repair cross‐complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility
Authors: Yang Fan , Mu Xiyan , Bian Ce , Zhang Huan , Yi Tao , Zhao Xia , Lin Xiaojuan
Published: May 2019

The role of excision repair cross‐complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta‐analysis to better clarify the association. Case‐control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case‐control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02‐1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12‐1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01‐1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02‐1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05‐1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12‐2.47; AA vs CC: OR = 1.72, 95% CI = 1.12‐2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta‐analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case‐control studies with well‐adjusted data and diverse populations are essential for validation of our conclusion.
Pancreatic β‐cell regeneration: From molecular mechanisms to therapy
Authors: Motlagh Roozbeh Akbari , Mohebbi Shabnam , Moslemi Maryam , Jabbari Parnia , Alizadeh Arezoo , Mardani Rajab , Gheibi hayat Seyed Mohammad
Published: May 2019

Pancreatic β cells are a type of cells that are present in the islets of Langerhans. These cells are highly specialized for the secretion of insulin in response to low increasing of blood glucose levels. Hence, pancreatic β cells could contribute to maintaining systemic glucose homeostasis. Increasing evidence has revealed that a variety of internal (ie, genetic and epigenetic factors) and external factors (ie, radical‐oxidative stress) are involved in the protection and/or regeneration of pancreatic β cells. The pathways regulating β‐cell replication have been intensely investigated. Glucose has an important role in cell cycle entry of quiescent β cells, which exerts its effect via glucose metabolism and unfolded proteins. A variety of growth factors, hormones, and signaling pathways (ie, calcium‐calcineurin nuclear factor of activated T cells) are others factors that could affect β‐cell replication under different conditions. Therefore, a greater understanding of the underlying pathways involved in the regeneration and protection of pancreatic β cells could lead to finding and developing new therapeutic approaches. Utilization of stem cells and various phytochemical agents have provided new aspects for preventing β‐cell degeneration and stimulating the endogenous regeneration of islets. Thus, these therapeutic platforms could be used as potential therapies in the treatment of insulin‐dependent diabetes mellitus. Here, we summarized the various mechanisms involved in pancreatic β‐cell regeneration. Moreover, we highlighted different therapeutic approaches which could be used for the regeneration of pancreatic β cells.
Phosphorylated mTORC1 represses autophagic‐related mRNA translation in neurons exposed to ischemia‐reperfusion injury
Authors: Hua Rongrong , Wei Haiping , Liu Chunyan , Shi Zhe , Xing Yan
Published: May 2019

Objectives

The sequential reactivation of mechanistic target of rapamycin (mTOR) inhibited autophagic flux in neurons exposed to oxygen‐glucose deprivation/reperfusion (OGD/R), which was characterized by reduction of autophagosome formation and restriction of autolysosome degradation. However, its detailed molecular mechanism was still unknown. In this study, we further explore the existing form of mTOR and its suppression on the transcriptional levels of related mRNA from neurons exposed to ischemia‐reperfusion injury.

Methods

The OGD/R or middle cerebral artery occlusion/reperfusion (MCAO/R)‐treated neurons was used to simulate ischemia/reperfusion injury
. Autophagy flux was monitored by means of microtubule‐associated protein 1 light chain 3 (LC3) and p62. The reactivation of mTOR was determined by phosphorylation of ribosomal protein S6 kinase 1 (S6K1). Then the inhibitors of mTOR were used to confirm its existence form. Finally, the mRNA transcription levels were analyzed to observe the negative regulation of mTOR.

Results

The sequential phosphorylation of mTOR contributed to the neuronal autophagy flux blocking. mTOR was re‐phosphorylated and existed as mTOR complex 1 (mTORC1), which was supported by phosphorylation of S6K1 at Thr 389 in neurons. In addition, the phosphorylation of S6K1 was decreased roughly by applying mTORC1 inhibitors, rapamycin and torin 1. However, the administration of mTORC1/2 inhibitor PP242 could recover the phosphorylation of S6K1, which suggested that mTORC2 was involved in the regulation of mTORC1 activity. In paralleling with reactivation of mTORC1, related mRNA transcription was repressed in neurons under ischemia‐reperfusion exposure in vivo and in vitro. The mRNA expression levels of LC3, Stx17, Vamp8, Snap29, Lamp2a, and Lamp2b were decreased in neurons after reperfusion, comparing with ischemia‐treated neurons.

Conclusions

The reactivated mTORC1 could suppress the transcription levels of related mRNA, such as LC3, Stx17, Vamp8, Snap29, Lamp2a, and Lamp2b. The research will expand the horizons that mTOR would negatively regulate autophagy at transcription and post‐translation levels in neurons suffering ischemia‐reperfusion injury.
Osthole inhibits osteoclasts formation and bone resorption by regulating NF‐κB signaling and NFATc1 activations stimulated by RANKL
Authors: Ma Yong , Wang Lining , Zheng Suyang , Xu Jiake , Pan Yalan , Tu Pengcheng , Sun Jie , Guo Yang
Published: May 2019

Chinese herbal medicine Fructus Cnidii has an outstanding effect on chronic lumbar pain and impotence, also has been used against osteoporosis with high frequency. Yet, the mechanisms of osthole, a derivative of Fructus Cnidii, on osteoclasts remains barely known. In this study, it was found out that osthole (10−6mol/L, 10−5mol/L) had the influence of inhibiting osteoclast formation and bone resorptive activities induced by receptor activator of nuclear factor κB ligand (RANKL), rather than affecting the viability of osteoclast‐like cells. Furthermore, osthole could also inhibit the messenger RNA expressions of c‐Src, tartrate‐resistant acid phosphatase, β3‐Integrin, matrix metallopeptidase 9, and cathepsin K. The results of the mechanistic study indicated that osthole regulated the nuclear factor of activated T‐cells cytoplasmic 1 (NFATc1) and nuclear factor‐κB (NF‐κB) activations following the RANKL stimulation.

These findings suggested that the inhibitory effects of osthole were associated with restraining the activations of NFATc1 and NF‐κB induced by RANKL. Thus osthole can be used as a potential treatment for abnormal bone‐resorption related diseases.
Biochemical evidence on the potential role of methyl mercury in hepatic glucose metabolism through inflammatory signaling and free radical pathways
Authors: Maqbool Faheem , Bahadar Haji , Hassani Shokoufeh , Niaz Kamal , Baeeri Maryam , Rahimifard Mahban , Ghasemi‐Niri Seyedeh Farnaz , Abdollahi Mohammad
Published: May 2019

Methylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6‐phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators’ cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8‐deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals.
The effects of delta‐9‐tetrahydrocannabinol on Krüppel‐like factor‐4 expression, redox homeostasis, and inflammation in the kidney of diabetic rat
Authors: Yanar Karolin , Coskun Zeynep Mine , Beydogan Alisa Bahar , Aydin Seval , Bolkent Sema
Published: May 2019

Diabetes mellitus is a complex, multifactorial disorder that is attributed to pancreatic β cell dysfunction. Pancreatic β cell dysfunction results in declining utilization of glucose by peripheral tissues as kidney and it leads to nephropathy. Excessive production and accumulation of free radicals and incapable antioxidant defense system lead to impaired redox status. Macromolecular damage may occur due to impaired redox status and also immune imbalance. Δ9‐Tetrahydrocannabinol (THC) is the main active ingredient in cannabis. THC acts as an immunomodulator and an antioxidant agent. Our aim was to evaluate the effects of THC in the diabetic kidney. We analyzed macromolecular damage biomarkers as protein carbonyl (PCO), lipid hydroperoxide (LHP), malondialdehyde (MDA), 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), and antioxidant defense system biomarkers as thiol fractions (T‐SH, NP‐SH, P‐SH) and Cu/Zn‐superoxide dismutase activity for the antioxidative effects of THC. Furthermore, mRNA expression of Krüppel‐like factor‐4, secreted immunopositive cell number changes of interleukin‐6, nuclear factor κβ (NF‐κβ), and peroxisome proliferator‐activated receptor‐γ and tumor necrosis factor α (TNF‐α) levels were analyzed for the immunomodulatory activity of THC. Diabetic rats showed significantly increased levels of PCO, LHP, MDA, and 8‐OHdG when compared with controls (P < 0.05 for each parameter). THC significantly reduced the elevated levels of PCO and 8‐OHdG (P < 0.05 for both parameters) and also LHP and MDA levels were insignificantly reduced by THC. Also, thiol fractions insignificantly increased in THC administered diabetic kidney when compared with diabetic rats. The NF‐κβ cell number significantly decreased in the diabetic rats treated with THC compared with the diabetic group. According to our data, THC has ameliorative effects on the impaired redox status of diabetic kidney and also it acts as an immunomodulator. Therefore, THC might be used as a therapeutic agent for diabetic kidneys but its usage in the healthy kidney may show adverse effects.
The molecular mechanism study of insulin in promoting wound healing under high‐glucose conditions
Authors: Wang Lin , Yang Bai , Jiang Hua , Yu Guo , Feng Mi , Lu Xingmei , Luo Qiang , Wu Hao , Zhang Shuo , Liu Hongchen
Published: May 2019

Background

Wound healing is a complex process in bone development. The aim of this study was to explore the molecular mechanism study of insulin in promoting wound healing.

Methods

Firstly, the acute human monocyte leukemia cell lines were induced to differentiate into macrophages. Secondly, the porphyromonas gingivalis was applied to mix with the differentiated macrophages. Thirdly, the effect of different concentrations of insulin (0 ng/mL, 5 ng/mL, 50 ng/mL, 100 ng/mL, 200 ng/mL, 500 ng/mL, and 1,000 ng/mL) on the phagocytosis of macrophages and production of reactive oxygen species was investigated. Depending on these experiments, the optimal insulin concentration was used to treat the macrophages at different time points (0 hours and 0.5 hours) to identify the differentially expressed mRNAs. Finally, functional analysis including gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein‐protein interaction (PPI) analysis was carried out to explore the biological function of these differentially expressed mRNAs.

Results

The test of phagocytosis function and production of reactive oxygen species showed that 200 ng/mL insulin treatment had a significant influence on antibacterial and production of reactive oxygen species. In RNA sequencing, a total of 415 (245 upregulated and 170 downregulated) differentially expressed mRNAs were identified between different time points. Two important signaling pathways including endocytosis and systemic lupus erythematosus were found in the KEGG enrichment analysis. In the PPI network, several hub proteins encoded by differentially expressed mRNA including ALB, HIP1R, RAB5A, HIST1H2BJ, HIST1H3G, and HIST1H2BO were identified.

Conclusion

Our work demonstrated that several differentially expressed mRNAs, such as EGR1, RAB34, ALB, HIP1R, RAB5A, HIST1H2BJ, HIST1H3G, and HIST1H2BO and two important signaling pathways including endocytosis and systemic lupus erythematosus may play important roles in the bone wound healing.
Prenatal liver stromal cells: Favorable feeder cells for long‐term culture of hepatic progenitor cells
Authors: Feizi Zahra , Zahmatkesh Ensieh , Farzaneh Zahra , Piryaei Abbas , Gramignoli Roberto , Nussler Andreas K. , Baharvand Hossein , Vosough Massoud
Published: May 2019

Clinical and pharmaceutical applications of primary hepatocytes (PHs) are limited due to inadequate number of donated livers and potential challenges in successful maintenance of PHs in culture. Freshly isolated hepatocytes lose their specific features and rapidly de‐differentiate in culture. Bipotent hepatoblasts, as liver precursor cells that can differentiate into both hepatocytes and cholangiocytes (Alb‐ and Ck19‐positive cells, respectively), could be used as an alternative and reliable cell source to produce enough PHs for drug discovery or possible clinical applications. In this study, growth factor‐free coculture systems of prenatal or postnatal murine liver stromal cells (pre‐LSCs or post‐LSCs, respectively) were used as feeder cells to support freshly isolated mice hepatoblasts. DLK1‐positive hepatoblasts were isolated from mouse fetuses (E14.5) and cocultured with feeder cells under adherent conditions. The hepatoblasts' bipotent features, proliferation rate, and colony formation capacity were assessed on day 5 and 7 post‐seeding. Immunoﬂuorescence staining showed that the hepatoblasts remained double positive for Alb and Ck19 on both Pre‐ and Post‐LSCs, after 5 and 7 days of coculture. Moreover, application of pre‐LSCs as feeder cells significantly increased the number of DLK1‐positive cells and their proliferation rate (ie, increased the number of Ki‐67 positive cells) on day 7, compared to Post‐LSCs group. Finally, to address our ultimate goal, which was an extension of hepatoblasts ex vivo maintenance, 3D spheres of isolated hepatoblasts were, cultured in conditioned medium (CM) derived from pre‐LSCs until day 30. It was observed that the CM derived from Pre‐LSCs could successfully prolong the maintenance of hepatic progenitor cells (HPCs) in 3D suspension culture.
Incorporated‐bFGF polycaprolactone/polyvinylidene fluoride nanocomposite scaffold promotes human induced pluripotent stem cells osteogenic differentiation
Authors: Abazari Mohammad Foad , Soleimanifar Fatemeh , Enderami Seyed Ehsan , Nematzadeh Mahsa , Nasiri Navid , Nejati Fatemeh , Saburi Ehsan , Khodashenas Shabanali , Darbasizadeh Behzad , Khani Mohammad Mehdi , Ghoraeian Pegah
Published: May 2019

Bioactive scaffolds that can increase transplanted cell survival time at the defect site have a great promising potential to use clinically since tissue regeneration or secretions crucially depend on the transplanted cell survival. In this study embedded basic fibroblast growth factor (bFGF)‐polycaprolactone‐polyvinylidene fluoride (PCL‐PVDF) hybrid was designed and fabricated by electrospinning as a bio‐functional nanofibrous scaffold for bone tissue engineering. After morphological characterization of the PCL‐PVDF (bFGF) scaffold, nanofibers biocompatibility was investigated by culturing of the human induced pluripotent stem cells (iPSCs). Then, the bone differentiation capacity of the iPSCs was evaluated when grown on the PCL‐PVDF and PCL‐PVDF (bFGF) scaffolds in comparison with culture plate as a control using evaluating of the common osteogenic markers. The viability assay displayed a significant increase in iPSCs survival rate when grown on the bFGF content scaffold. The highest alkaline phosphatase activity and mineralization were detected in the iPSCs while grown on the PCL‐PVDF (bFGF) scaffolds. Obtained results from gene and protein expression were also demonstrated the higher osteoinductive property of the bFGF content scaffold compared with the scaffold without it. According to the results, the release of bFGF from PCL‐PVDF nanofibers increased survival and proliferation rate of the iPSCs, which followed by an increase in its osteogenic differentiation potential. Taking together, PCL‐PVDF (bFGF) nanofibrous scaffold demonstrated that can be noted as a promising candidate for treating the bone lesions by tissue engineering products.
Novel key genes in triple‐negative breast cancer identified by weighted gene co‐expression network analysis
Authors: Chen Jian , Qian Xiaojun , He Yifu , Han Xinghua , Pan Yueyin
Published: May 2019

Triple‐negative breast cancer (TNBC) is a special subtype of breast cancer (BC) with poor prognosis. Although some molecular mechanisms of TNBC have been elucidated, the efficacy of current treatments is limited. Therefore, it is urgently demanded to screen for novel biomarkers and drug targets for TNBC. In this study, we obtained four independent data sets (GSE76250, GSE31448, GSE43358, and METABRIC) from the Gene Expression Omnibus (GEO) database and the cBioPortal website. In the GSE76250 data set, 890 differentially expressed genes were identified and weighted gene co‐expression network analysis was performed based on them. Then, two preserved modules associated with the KI67 score were detected. Gene ontology and pathway enrichment analyses showed genes in the modules participated in some cancer‐related biological processes or pathways. Non‐SMC condensin I complex subunit G (NCAPG) and ATP‐binding cassette subfamily A member 9 (ABCA9) were identified as hub genes of the modules, and the significance of hub genes was validated in the GSE43358 data set. Finally, their prognostic value was assessed by survival analysis. These findings suggested that NCAPG and ABCA9 may be the key genes of TNBC. Moreover, ABCA9 was first reported in TNBC. They deserved further studies.
Long intergenic noncoding RNA p21 suppresses the apoptosis of hippocampus neurons in streptozotocin‐diabetic mice by sponging microRNA‐221 through upregulation of FOS
Authors: Sun Qin , Zeng Qing‐Cui , Chen Yan‐Qiu , Zhang Min , Wei Ling‐Ling , Chen Ping
Published: May 2019

Diabetes is associated with neurological complications, and accumulated evidence shows that biological pathways in diabetes are targeted by noncoding RNA transcripts. In this study, the role of long intergenic noncoding RNA (lincRNA) p21/microRNA‐221 (miR‐221)/fructooligosaccharide (FOS) axis was investigated in the mice with diabetes treatment. The streptozotocin‐induced diabetic mouse model was established. The learning ability and the pathological changes in mice were analyzed. After that, the interaction among miR‐221, lincRNA p21, and FOS was explored and verified. The subcellular location of lincRNA p21 was identified. Finally, the cell cycle and apoptosis of the hippocampus neurons were measured. In the diabetic mice, the levels of blood glucose were higher and the leaning abilities were inhibited. miR‐221 was highly expressed in the diabetic mice whereas lincRNA p21 and FOS were poorly expressed. miR‐221 could bind with both lincRNA p21 and FOS. miR‐221 silencing or lincRNA p21 overexpression in the diabetes mice reduced the cell apoptosis rate, and the expression of Bax and cleaved Caspase‐3, whereas increase the Bcl‐2 expression. Overexpression of lincRNA p21 promotes FOS expression by binding to miR‐221, thereby, inhibiting hippocampal neuron apoptosis in diabetic mice. This may offer potential targets for diabetes.
“In‐loop” 18F‐fluorination: A proof‐of‐concept study
Authors: Dahl Kenneth , Garcia Armando , Stephenson Nickeisha A. , Vasdev Neil
Published: May 2019

There is a great demand to develop more cost‐efficient and robust manufacturing processes for fluorine‐18 (18F) labelled compounds and radiopharmaceuticals. Herein, we present to our knowledge the first radiofluorination “in‐loop,” where [18F]triflyl fluoride was used as the labelling agent. Initial development of the “in‐loop” [18F]fluorination method was optimized by reacting [18F]triflyl fluoride with 1,4‐dinitrobenzene to form [18F]1‐fluoro‐4‐nitrobenzene. This methodology was then applied for the syntheses of two well‐known radiopharmaceuticals, namely, [18F]T807 for imaging of tau protein and [18F]FEPPA for imaging the translocator protein 18 KDa. Both radiotracers were synthesized and formulated using an automated radiosynthesis module with nondecay corrected radiochemical yields of 27% and 29% (relative [18F]F−), respectively. The overall syntheses times for [18F]T807 and [18F]FEPPA were 65 and 55 minutes, respectively. In these cases, our “in‐loop” radiofluorination methodology enabled us to obtain equal or superior yields compared with conventional reactions in a vial. The radiochemical purities were more than 99%, and the molar activities were more than 350 GBq/μmol at the end‐of‐synthesis for both radiotracers. This novel method is simple, efficient, and allows for a reliable production of radiofluorinated compounds and radiopharmaceuticals.
Naloxone reversed cognitive impairments induced by repeated morphine under heavy perceptual load in the 5‐choice serial reaction time task
Authors: Guo Hao , Xie Qiaoli , Cui Jingjing , Xu Dan , Deji Cuola , Chen Yuanyuan , Wang Yunpeng , Lai Jianghua
Published: May 2019

Repeated opioids abuse may produce long‐lasting and complicated cognitive deficits in individuals. Naloxone is a typical mu‐opioid receptor antagonist widely used in clinical treatment for opioid overdose and opioid abuse. However, it remains unclear whether naloxone affects morphine‐induced cognitive deficits. Using the 5‐choice serial reaction time task (5‐CSRTT), the present study investigated cognitive profiles including attention, impulsivity, compulsivity, and processing speed in repeated morphine‐treated mice. Repeated morphine administration (10 mg/kg, i.p.) induced complex cognitive changes including decreased attention and increased impulsivity, compulsivity, processing speed. Systemic naloxone administration (5 mg/kg, i.p.) reversed these cognitive changes under the heavy perceptual load in 5‐CSRTT. Using the novel object recognition (NOR), Y‐maze and open‐field test (OFT), the present study investigated the memory ability and locomotor activity. Naloxone reversed the effect of morphine on recognition memory and locomotion but had no effect on working memory. In addition, repeated morphine administration decreased the expression of postsynaptic density protein 95 (PSD95) and cAMP response element binding protein (CREB) phosphorylation in the prefrontal cortex (PFC) and hippocampus (HIP), and these effects were significantly reversed by naloxone in PFC. Our study suggests that repeated exposure to morphine affects multiple cognitive aspects and impairs synaptic functions. Systemic naloxone treatment reverses the mu‐opioids‐induced cognitive changes, especially under the heavy perceptual load, possibly by restoring the synaptic dysfunctions.