bluuebunny/crossref_metadata_2025 huggingface dataset:
Diselenolane‐Mediated Cellular Uptake: Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein‐Coated Quantum Dots
Authors: Bartolami Eline , Basagiannis Dimitris , Zong Lili , Martinent Rémi , Okamoto Yasunori , Laurent Quentin , Ward Thomas R. , Gonzalez‐Gaitan Marcos , Sakai Naomi , Matile Stefan
Published: February 2019

Cyclic oligochalcogenides are emerging as powerful tools to penetrate cells. With disulfide ring tension maximized, selenium chemistry had to be explored next to enhance speed and selectivity of dynamic covalent exchange on the way into the cytosol. We show that diseleno lipoic acid (DiSeL) delivers a variety of relevant substrates. DiSeL‐driven uptake of artificial metalloenzymes enables bioorthogonal fluorophore uncaging within cells. Binding of a bicyclic peptide, phalloidin, to actin fibers evinces targeted delivery to the cytosol. Automated tracking of diffusive compared to directed motility and immobility localizes 79 % of protein‐coated quantum dots (QDs) in the cytosol, with little endosomal capture (0.06 %). These results suggest that diselenolanes might act as molecular walkers along disulfide tracks in locally denatured membrane proteins, surrounded by adaptive micellar membrane defects. Miniscule and versatile, DiSeL tags are also readily available, stable, soluble, and non‐toxic.
The Construction of Molecular Complexity from Functionalized Alkylidenecyclopropanes (FACPs)
Authors: Yu Liu‐Zhu , Shi Min
Published: February 2019

As a special family of cyclopropanes, alkylidenecyclopropanes (ACPs), exhibit outstanding physical and chemical activities, which provide opportunities to participate in fascinating chemical transformations to access cyclopropane‐containing units without ring‐opening processes and other unavailable compounds through conventional routes with ring‐opening processes owing to their strain‐driven reactivity and synthetic accessibility. Nowadays, intramolecular reactions of methylenecyclopropanes (MCPs) or ACPs with adjacent functionalities have emerged as a powerful synthetic protocol for the construction of a variety of polycyclic and heterocyclic compounds with different sized skeletons through catalytic methods. Recently, we put forward the concept of functional alkylidenecyclopropanes (FACPs) and in this Minireview, we will summarize the reactions of FACPs after 2016 including several important early works from three aspects: 1) reactions with distal C−C bond cleavage, 2) reactions with proximal C−C bond cleavage (including ring‐expansion reactions), and 3) reactions without C−C bond cleavage.
Development of Chiral Spiro Phosphoramidites for Rhodium‐Catalyzed Enantioselective Reactions
Authors: Zheng Zhiyao , Cao Yuxi , Zhu Dongsheng , Wang Zheng , Ding Kuiling
Published: February 2019

A series of 1,1′‐spirobiindane‐7,7′‐diol (SPINOL) analogues bearing a 2,2′‐dimethyl‐, cyclopentyl‐, or cyclohexyl‐fused ring were synthesized, and their distinct structural features were elucidated by X‐ray crystallography. On the basis of these scaffolds, chiral monophosphoramidite ligands 6 a–m were synthesized, which demonstrated excellent enantioselectivity in RhI‐catalyzed asymmetric hydrogenation of a dehydro amino acid methyl ester. Ligands 6 a–m were also successfully applied in the RhI‐catalyzed enantioselective [4+2] cycloaddition of α,β‐unsaturated imines with isocyanates, which afforded the corresponding pyrimidinones in good yields (60–92 %) with high enantioselectivities (75–92 % ee).
Copper‐Catalyzed Carbotrifluoromethylation of Unactivated Alkenes Driven by Trifluoromethylation of Alkyl Radicals
Authors: Zhang Zhenzhen , Zhu Lin , Li Chaozhong
Published: February 2019

Summary of main observation and conclusion

We report herein an unprecedented protocol for radical carbotrifluoromethylation of unactivated alkenes. With Cu(OTf)2 as the catalyst, the reaction of unactivated alkenes, TMSCF3 and activated alkyl chlorides at room temperature provides the corresponding carbotrifluoromethylation products in satisfactory yields. Directed by trifluoromethylation of alkyl radicals, the method exhibits an excellent regioselectivity that is opposite to those driven by CF3 radical addition.
Novel Approaches to Access Arylfluorosulfates and Sulfamoyl Fluorides Based on Sulfur (VI) Fluoride Exchange
Authors: Liu Zilei , Meng Genyi , Guo Taijie , Dong Jiajia , Wu Peng
Published: February 2019

Sulfur (VI) fluoride exchange (SuFEx) is a new family of click chemistry reactions that relies on readily available sulfuryl fluoride (SO2F2) and ethenesulfonyl fluoride to build diverse chemical structures bearing the SVI‐F motif, such as fluorosulfate (‐OSO2F) and sulfonyl fluoride (‐SO2F). These motifs could be useful functional groups and connective linkers in organic synthesis. This unit describes two protocols for performing SuFEx. The first protocol describes an in situ method for rapid generation of arylfluorosulfates in 96‐well plates for high‐throughput screening. The second protocol outlines use of a shelf‐stable fluorosulfuryl imidazolium salt for generating arylfluorosulfates and sulfamoyl fluorides. © 2019 by John Wiley & Sons, Inc.
Predictive model for hardware calibration to transmit real‐time applications in VoIP networks
Authors: Gupta Nishant , Mahajan Nitish , Kaushal Sakshi , Kumar Naresh , Kumar Harish , Sangaiah Arun Kumar
Published: February 2019

Voice over Internet Protocol (VoIP) carries and transforms voice over the IP networks. The principles of VoIP calls are similar to traditional telephony that involves signalling, channel‐setup, digitization, and encoding of speech signal, but it transmits data over a packet‐switched network instead of circuit‐switched network. Factors which determine VoIP Quality of Service (QoS) include the choice of codec, packet loss, delay, jitter, and optimal hardware selection to handle different services. Hardware Calibration is a mechanism used for selecting an appropriate hardware for call manager to process and transmit different applications in real time. The widespread use of VoIP services in formal and informal sector produces a significant amount of data with variety of dimensions. This data can be used as leverage to analyze the system and predict various factors boosting the performance and cost effectiveness of the system. This paper proposes a predictive model that selects the best suitable hardware to handle particular offered load, which can support desired numbers of concurrent calls from wide array of processors available in the market today. This model would help the VoIP service providers in providing efficient services with QoS for different VoIP services like voice, data, video, chat, etc. This paper attempts to train and evaluate a model using various system parameters and system benchmark is predicted on an absolute scale. The results effectively demonstrate the selection of best call manager to handle offered load and hence provides QoS in overall network performance.
Efficient hash function–based duplication detection algorithm for data Deduplication deduction and reduction
Authors: Periasamy J.K. , Latha B.
Published: February 2019

Data Deduplication is the foremost technique used for data compression by removing redundant data. It is broadly utilized for cloud storage server, which reduces the un‐utilized memory space and optimized bandwidth. The confidentiality of sensitive information maintains during Deduplication detection. The Efficient Hash Function–based Duplication Detection (EHFDD) algorithm is proposed to encrypt the content before outsourcing in cloud environment. This paper is an attempt to enhance the data security and notify the issues of approved data Deduplication detections. Furthermore, it also presents several novel Deduplication improvisations for helping certified duplicate verification in hybrid cloud. The EHFDD method enables duplicate detection scheme with minimal overhead compared to existing functions. Based on experimental evaluations, proposed EHFDD algorithm reduces the average delay in 28.7 milliseconds, memory utilization in 8%, computation time in 457 milliseconds, communications overhead in 900 milliseconds, and improves the success rate in 3.13%.
New Kids in Lactide Polymerization: Highly Active and Robust Iron Guanidine Complexes as Superior Catalysts
Authors: Rittinghaus Ruth D. , Schäfer Pascal M. , Albrecht Pascal , Conrads Christian , Hoffmann Alexander , Ksiazkiewicz Agnieszka N. , Bienemann Olga , Pich Andrij , Herres‐Pawlis Sonja
Published: February 2019

Polylactide is a biodegradable versatile material based on annually renewable resources and thus CO2‐neutral in its lifecycle. Until now, tin(II)octanoate [Sn(Oct2)] was used as catalyst for the industrial ring‐opening polymerization of lactide in spite of its cytotoxicity. On the way towards a sustainable catalyst, three iron(II) hybrid guanidine complexes were investigated concerning their molecular structure and applied to the ring‐opening polymerization of lactide. The complexes could polymerize unpurified technical‐grade rac‐lactide as well as recrystallized l‐lactide to long‐chain polylactide in bulk with monomer/initiator ratios of more than 5000:1 in a controlled manner following the coordination–insertion mechanism. For the first time, a biocompatible complex has surpassed Sn(Oct)2 in its polymerization activity under industrially relevant conditions.
Deconstructing the policyscape for reducing deforestation in the Eastern Amazon: Practical insights for a landscape approach
Authors: Gebara Maria Fernanda , Sills Erin , May Peter , Forsyth Tim
Published: February 2019

In international debates on climate change mitigation and forests, there is increased recognition of the importance of a landscape approach to effectively address tropical deforestation. Such an approach, although increasingly promoted, remains only loosely defined and requires further development in order to effectively integrate different interventions at landscape level. In particular, it is important to understand the possible interactions between different landscape interventions at local level—where they are intended to have effect—and the challenges associated with them. Inspired by the complexity of policy mix analysis, this article seeks to shed light on these interactions by analysing how different policies and measures for reducing deforestation and degradation have played out in a jurisdiction with wide‐ranging actors and interventions aimed at shaping their behaviour. Focusing on smallholders, we examine the Sustainable Landscapes Pilot Programme in São Félix do Xingu, looking at how different policies interact—categorising interactions as “complementary,” “mutually reinforcing” (synergistic), “in conflict,” “interdependent,” and/or “redundant”—and explain how proponents of this pilot programme seek to integrate them. Most analysis is based on primary data collected through quantitative (i.e., random stratified sampling and surveys) and qualitative (i.e., observation and focus groups) methods. The São Félix do Xingu case shows that understanding effects of different policies and measures on people's behaviour requires a deeper look at local perceptions and reactions to such policies and measures, something most studies on the topic have overlooked. Ultimately, the heterogeneity and complexity of social practices that permeate landscapes must be recognised in order to integrate diverse measures to reduce deforestation.
Public trust thinking and public ownership of wildlife in Italy and the United States
Authors: Giacomelli Stefano , Hare Darragh , Gibbert Michael , Blossey Bernd
Published: February 2019

Wildlife laws codify normative aspirations to conserve species. However, species continue to decline or disappear, highlighting a disconnect between normative aspirations and conservation outcomes. Public trust thinking (PTT) is a philosophical approach to natural resources, including wildlife, characterized by commitments to public control, broad public interests, and conservation for future generations. Elements of PTT feature in natural resource governance traditions across cultures and over time, notably in the common‐law public trust doctrine (PTD). We ask whether PTT's foundational principles inform public wildlife governance in Italy, a civil law country where wildlife is publicly owned but PTD does not exist. We identify all five foundational principles of PTT in elements of Italian law and policy and compare them with examples from the United States, where PTD for wildlife is more firmly established. We argue that a de facto public trust exists in Italian legal and policy aspirations, but meeting these aspirations is inhibited by absence of clear legal responsibilities and constructive, inclusive public engagement processes. By establishing that similar aspirations exist in both countries despite differences in legal histories and institutional architectures, we support claims that functional equivalents of PTD exist in civil law traditions and lend weight to recent proposals to use PTT to guide creative wildlife governance reform outside of common‐law systems. Specifying precise responsibilities for public wildlife administrators across levels of governance will be essential to connect normative aspirations with conservation outcomes.
Addressing the gap between participatory ideals and the reality of environmental management: The case of the cormorant population in Finland
Authors: Nordberg Kenneth , Salmi Pekka
Published: February 2019

Environmental management, similar to public management generally, is increasingly challenged by an ever more complex society. Generally, in scientific literature, participatory features are presented as solutions for adapting centrally steered management to local circumstances and for mitigating conflicts. This article argues that local realities and transformations are easily neglected in environmental management due to unsuccessful implementation of its own participatory ideals. By studying the management of cormorant–human conflicts in Finland, the article identifies critical features that can be implemented to overcome the gap between participatory ideals and the reality of environmental management. By interviewing locals and civil servants and by directing questionnaires to fishers, the article presents how management and science look for dependencies between cormorants, fish stocks, and water nutrition, although fishers and locals are primarily concerned with the combination of seal‐ and cormorant‐induced damages, the changed behaviour of fish, and reduced recreational possibilities. Narrow scientific approaches and the national interpretation of the EU Birds directive thereby impede the management system from perceiving the complete local impact of a growing cormorant population. This article identifies obstacles hindering a balanced environmental management policy and concludes that there is a need to reinforce (a) social scientific approaches; (b) vertical negotiations at the local, national, and supranational level; and (c) the training of civil servants as facilitators of communication.
N‐Doped Carbon Wrapped Polyoxometalate Derived from POM‐IL Hybrid: A Heterogeneous Catalyst for the Synthesis of Coumarin Derivatives under Solvent‐Free Conditions
Authors: Ramalingam Meenakshi , Mani Chandhru , Manickam Sundar , Srinivasalu Kutti Rani
Published: February 2019

Vanadium substituted Keggin type polyoxometalate loaded N‐doped carbon was prepared from polyoxometalate ionic liquid hybrid by carbonization process. The decomposition of organic part generates various functional groups leaving polyoxometalate part intact. The catalyst was characterized by elemental analysis, FTIR, MAS 13C NMR, XPS and electron microscopy studies. The presence of carboxylic acids, aromatic and hetero‐aromatic groups in the catalyst was confirmed by 13C NMR. The high resolution C1s and O1s XPS analysis further confirmed the presence of these groups. Various oxidation states of nitrogen were confirmed by deconvoluted N1s XPS spectra. Pyridine adsorption study confirms the presence of Bronsted and Lewis acid sites in the catalyst. Layered structure of the catalyst was confirmed by HR TEM analysis. The hybrid material displayed excellent catalytic activity towards the synthesis of coumarin derivatives under solvent‐free conditions.
Phosphophosphidites Derived from BINOL
Authors: Gorman Adam D. , Cross Jessica A. , Doyle Rachel A. , Leonard Tom R. , Pringle Paul G. , Sparkes Hazel A.
Published: February 2019

Phosphophosphidites of the type R2P–P(binol) [where binol = the dianion of (S)‐1,1′‐bi‐2‐naphthol] are the phosphorus analogues of the ubiquitous phosphoramidites, R2N–P(binol) and are readily accessed by the chlorosilane elimination reaction between R2P–SiMe3 and Cl–P(binol). The crystal structure of iPr2P–P(binol) (1) has been determined and shows a P–P bond length in the normal range. The solution reactions of 1 have been investigated, principally by 31P NMR spectroscopy which has revealed that: (a) in contrast to the phosphoramidites, 1 is extremely moisture sensitive; (b) the P–P bond in 1 is cleaved upon reaction with H2O, MeOH or mesitol; (c) the P–O bonds in 1 are cleaved upon reaction with pyrrolidine; (d) the integrity of 1 is retained upon coordination to BH3 or Mo0. The crystal structure of cis‐[Mo(CO)4(1)2] shows that 1 is bound to the Mo at the P(binol) site and the νCO of 2032 cm‐1 indicates that 1 has similar ligand properties to a phosphonite.
Cobalt(III)‐Catalyzed Direct ortho‐Alkenylation of Arylpyrazoles: A Comparative Study on Decarboxylation and Desilylation
Authors: Kumar Anil , Muniraj Nachimuthu , Prabhu Kandikere Ramaiah
Published: February 2019

A comparative study on CoIII‐catalyzed direct C–H bond alkenylation of 1‐phenylpyrazole derivatives with alkynyl carboxylic acids and arylalkynylsilanes under redox‐neutral conditions has been disclosed. These methods show excellent selectivity with good to excellent yields. Trimethylsilylacetylene has been utilized as a vinyl source to obtain the corresponding styrene derivatives. The major differences between these two reactions are the decarboxylation proceeds in the presence of a base additive whereas the desilylation takes place in the presence of an acid additive. The developed methodologies are compatible with a variety of functional groups.
An Enantiopure Cyclometallated Iridium Complex Displaying Long‐Lived Phosphorescence both in Solution and in the Solid State
Authors: Macé Aurélie , Hellou Nora , Hammoud Joanna , Martin Clothilde , Gauthier Etienne S. , Favereau Ludovic , Roisnel Thierry , Caytan Elsa , Nasser Ghassan , Vanthuyne Nicolas , Williams J. A. Gareth , Berrée Fabienne , Carboni Bertrand , Crassous Jeanne
Published: February 2019

A new enantiopure cyclometallated iridium complex bearing a [4]helicenic
‐coordinating and two
‐coordinating dfppy (2‐(2,4‐difluorophenyl)‐pyridyl) ligands was prepared. This complex displayed long‐lived phosphorescence both in solution and in the solid state. Its chiroptical properties, namely electronic circular dichroism and circularly polarized luminescence, were also examined. Comparison with former chiral complexes enabled assignment of the ΔIr‐(−) and ΛIr‐(+) absolute configurations.
Novel numerical solutions of nonlinear heat transfer problems using the linear barycentric rational interpolation
Authors: Torkaman Soraya , Loghmani Ghasem B. , Heydari Mohammad , Rashidi Mohammad Mehdi
Published: February 2019

In this investigation, a numerical technique to obtain the approximate solutions of four well‐known nonlinear differential equations in the area of heat transfer is presented. This method is based on the operational matrix of derivative of linear barycentric rational interpolation. The main advantages of this approach are that it uses the Floater‐Hormann weights, which are very efficient in practice, and reduces the governing differential equation to a system of algebraic equations. The results are compared with the obtained numerical results of the fourth‐order Runge‐Kutta method along with the shooting method and some of the previously existing methods. The acquired results reveal that the derivative operational matrix method with barycentric rational basis functions is very efficient and can be implemented easily and fast.
Comparative evaluation of the polynomial and spline fitting methods for the B0 correction of CEST MRI data acquired from human brains
Authors: Yoo Chang Hyun , Oh Janghoon , Park Soonchan , Ryu Chang‐Woo , Kwon Young Kyun , Jahng Geon‐Ho
Published: February 2019

To compare the magnetization transfer ratio asymmetry (MTRasym) values calculated with polynomial and spline fitting methods for B0 correction of the full Z‐spectrum images, full Z‐spectrum data was obtained from 12 elderly healthy subjects by using a 3D segmented EPI sequence, as well as from 17 other subjects by using a 3D GRASE sequence with two different 3 T MRI systems. The full Z‐spectra were analyzed to map MTRasym with three different fitting methods, namely the 10th and 14th polynomial and spline methods, for B0 correction. The MTRasym values for each offset frequency were compared among the three fitting methods. For the 3D segmented EPI sequence, the MTRasym values significantly differed among the three fitting methods at 0.86, 2.14, 3.00, and 3.43 ppm offset frequencies. For the 3D GRASE sequence, the MTRasym values obtained by 14th polynomial and spline fitting methods significantly differed at arbitrary offset frequencies. The MTRasym values are sensitive to the fitting methods of B0 correction and to the type of acquisition sequence for the full Z‐spectrum. Therefore, an appropriate fitting method should be used to analyze the full Z‐spectrum obtained from the brain.
The effects of type I collagen on bone defects and gene expression changes for osteogenesis: In a rat model
Authors: Yiğiter Özgür , Yorukoglu Ali Cagdas , Şentürk Nilay , Dodurga Yavuz , Demirkan Ahmet Fahir
Published: February 2019

The aim of this study is to investigate the effects of type I collagen on bone defects and on genes specifically for osteogenesis in a rat model. Two millimeter drill hole bone defect was created in the femur of rats. In the experimental group, type I collagen was applied in bone defects whereas in control group defects were left empty. Inflammation, development of connective tissue, osteogenesis, and foreign body reaction parameters evaluated with histologically and genes evaluated by blood samples. In the experimental group, the histopathologically significant change was found in favor of bone healing only at the first week. A significant increase was found in genetic expressions of BMP‐1, 2, 3, 4, 5, 6, 7, TGF‐βRII, Smad‐1, IL‐6, BMPR‐IA, BMPR‐IB, Eng, BMPR‐II, c‐fos, Cdkn1a, Chrd, Gdf‐5, Id‐1, PDGF‐β, IGF‐1, Serpine‐1, and TGF‐βRI at the first hour. At the first, third, and sixth week, no significant increase was found in any of the gene expressions. Type I collagen is found to be effective in favor of bone healing through increased inflammatory cytokines and expression of BMP genes in the early stages of fracture healing.
Network pharmacology‐based research on the active component and mechanism of the antihepatoma effect of Rubia cordifolia L.
Authors: Xiong Yiyi , Yang Yanfang , Xiong Weichen , Yao Yunfeng , Wu Hezhen , Zhang Meide
Published: February 2019

Rubia cordifolia L. is widely used in Asia and its antihepatoma effect has been proved by in vitro and in vivo experiments. However, there are few studies on its specific mechanism. In the present study, the network pharmacology method was used to construct the component/target/pathway molecular regulatory network for the antihepatoma effect of
Rubia cordifolia L. to explore the effective components of
Rubia cordifolia L. and its potential mechanism. The chemical components of
Rubia cordifolia L. were identified through literature and databases, and the components were evaluated and screened by drug likeness and pharmacokinetic characteristics (ADMET). The targets of active components were predicted according to the reverse pharmacophore matching model. The hepatic carcinoma‐related genes were found in databases, and antihepatoma‐related gene targets were selected through comparison. The functions of target genes and related pathways were analyzed and screened using the Database for Annotation, Visualization and Integrated Discovery, and the component/target/pathways network of antihepatoma effect of
Rubia cordifolia L. was constructed using Cytoscape software. Finally, 16 active compounds were screened from
Rubia cordifolia L., and 39 gene targets, including AKT1, mitogen‐activated protein kinase 1, and epidermal growth factor receptor, were involved.
Rubia cordifolia L. also affected the hepatitis B, phosphoinositide‐3‐kinase‐protein kinase B, and mitogen‐activated protein kinase signaling pathways. Many direct‐acting tumor‐related signaling pathways and indirect‐acting hepatitis pathways inhibit the generation of liver cancer. The present study provided a scientific basis for further elucidating the mechanism of
Rubia cordifolia L. against liver cancer.
Confirmatory validation of the factor structure and psychometric properties of the Difficulties in Emotion Regulation Scale‐Positive
Authors: Weiss Nicole H. , Darosh Angela G. , Contractor Ateka A. , Schick Melissa M. , Dixon‐Gordon Katherine L.
Published: February 2019

Objectives

Emotion dysregulation is a transdiagnostic factor central to the etiology and treatment of various clinical difficulties. Yet, research in this area has focused almost exclusively on emotion dysregulation stemming from negative emotions. The current study confirmed the factor structure of the Difficulties in Emotion Regulation Scale‐Positive (DERS‐P) and further examined its reliability and validity.

Method

Participants in Study 1 were 229 college students (Mage = 19.37 years; 66.8% female; 67.2% White). Participants in Study 2 were 353 trauma‐exposed community individuals (Mage = 35.77 years; 57.8% female; 71.2% White).

Results

Findings supported the three‐factor structure of the DERS‐P. Mean levels of the DERS‐P scales demonstrated convergent and discriminant validity and differentiated individuals with (vs. without) probable posttraumatic stress disorder, depression, alcohol use, and drug use disorders.

Conclusions

Findings provide additional support for the factor structure, reliability, and validity of the DERS‐P, thereby adding to its clinical utility.
Tiliroside is a new potential therapeutic drug for osteoporosis in mice
Authors: Li Kai , Xiao Yu , Wang Ziyi , Fu Fangsheng , Shao Siyuan , Song Fangming , Zhao Jinmin , Lin Xixi , Liu Qian , Xu Jiake
Published: February 2019

Osteoporosis is a class of metabolic bone disease caused by complexed ramifications. Overactivation of osteoclasts due to a sudden decreased estrogen level plays a pivotal role for postmenopausal women suffering from osteoporosis. Therefore, inhibiting osteoclast formation and function has become a major direction for the treatment of osteoporosis. Tiliroside (Tle) is a salutary dietary glycosidic flavonoid extracted from Oriental Paperbush flower, which has been reported to have an anti‐inflammation effect. However, whether Tle affects the osteoclastogenesis and bone resorption remains unknown. Herein, we demonstrate that Tle prevents bone loss in ovariectomy in mice and inhibits osteoclast differentiation and bone resorption stimulated by receptor activator of nuclear factor‐κB ligand (RANKL) in vitro. Molecular mechanism studies reveal that Tle reduces RANKL‐induced activation of mitogen‐activated protein kinase and T‐cell nuclear factor 1 pathways, and osteoclastogenesis‐related marker gene expression, including cathepsin K (Ctsk), matrix metalloproteinase 9, tartrate‐resistant acid phosphatase (Acp5), and Atp6v0d2. Our research indicates that Tle suppresses osteoclastogenesis and bone loss by downregulating the RANKL‐mediated signaling protein activation and expression. In addition, Tle inhibits intracellular reactive oxygen species generation which is related to the formation of osteoclasts. Therefore, Tle might serve as a potential drug for osteolytic disease such as osteoporosis.
A negative feedback loop of H19/miR‐675/EGR1 is involved in diabetic nephropathy by downregulating the expression of the vitamin D receptor
Authors: Fan WenXing , Peng YunZhu , Liang Zhang , Yang YueNa , Zhang Jing
Published: February 2019

Aim

We aimed to explore the regulatory relationship among the long noncoding RNA H19, micorRNA‐675 (miR‐675), the vitamin D (VD) receptor (VDR), and the early growth response protein 1 (EGR1) in the pathogenesis of diabetic nephropathy (DN) among patients with diabetes mellitus (DM).

Methods

Expression levels of H19, miR‐675, VDR, and EGR in patients or CIHP‐1/HEK 293 cells were measured via quantitative reverse‐transcription polymerase chain reaction and western blot analysis. Computational analysis and luciferase assays were performed to determine EGR1 as a target gene of miR‐675.

Results

The relative expression of miR‐675 was higher in the presence of H19, whereas the expression of both VDR and EGR1 messenger RNA was decreased in the presence of H19 or miR‐675. However, relative expression of H19 and miR‐675 was increased, whereas VDR expression was suppressed upon the treatment of 1,25‐dihydroxyvitamin D3 or EGR1. VDR was identified as a target gene of miR‐675. The H19 promoter and EGR1 increased the luciferase activity of cells transfected with wild‐type VDR. Compared with DM patients free of DN, the levels of H19 and miR‐675 were increased in the DN(+) group, whereas the levels of VDR and EGR1 were decreased.

Conclusion

In summary, the above results indicate the presence of a negative feedback loop in the pathological mechanism of DN, where H19 downregulates the expression of VDR by upregulating the expression of miR‐675, whereas reduced VDR expression subsequently reduced the expression of EGR1. Moreover, reduced EGR1 expression inhibits H19 expression, thus forming a negative feedback loop required to maintain the homeostasis of VDR and to reduce the incidence of DN.
Amino acid restriction increases β‐cell death under challenging conditions
Authors: Mateus Gonçalves Luciana , Vettorazzi Jean Franciesco , Vanzela Emerielle Cristine , Figueiredo Mariana Sarto , Batista Thiago Martins , Zoppi Claudio Cesar , Boschero Antonio Carlos , Carneiro Everardo Magalhães
Published: February 2019

Malnutrition programs metabolism, favor dysfunction of β cells. We aimed to establish an in vitro protocol of malnutrition, assessing the effect of amino acid restriction upon the β cells. Insulin‐producing cells INS‐1E and pancreatic islets were maintained in RPMI 1640 medium containing 1× (Ctl) or 0.25× (AaR) of amino acids. We evaluated several markers of β‐cell function and viability. AaR Insulin secretion was reduced, whereas cell viability was unaltered. Calcium oscillations in response to glucose increased in AaR. AaR showed lower Ins1 RNAm, snap 25, and PKC (protein kinase C) protein content, whereas phospho‐eIF2α was increased. AaR cells exposed to nutrient or chemical challenges displayed higher apoptosis rates. We showed that amino acid restriction programmed β cell and induced functional changes. This model might be useful for the study of molecular mechanisms involved with β‐cell programming helping to establish novel therapeutic targets to prevent harmful outcomes of malnutrition.
Daphnetin attenuates LPS‐induced osteolysis and RANKL mediated osteoclastogenesis through suppression of ERK and NFATc1 pathways
Authors: Wu Zuoxing , Wu Hailun , Li Chen , Fu Fangsheng , Ding Jiaxin , Shao Siyuan , Li Kai , Yu Xiao , Su Yuangang , Liang Jiamin , Lin Xixi , Yuan Guixin , Zhou Juan , Song Fangming , Zhao Jinmin , Xu Jiake , Liu Qian , Xu Feng
Published: February 2019

Aseptic prosthetic loosening and periprosthetic infection resulting in inflammatory osteolysis is a leading complication of total joint arthroplasty (TJA). Excessive bone destruction around the bone and prosthesis interface plays a key role in the loosening prostheses leading to revision surgery. The bacterial endotoxins or implant‐derived wear particles‐induced inflammatory response is the major cause of the elevated osteoclast formation and activity. Thus, agents or compounds that can attenuate the inflammatory response and/or inhibit the elevated osteoclastogenesis and excessive bone resorption would provide a promising therapeutic avenue to prevent aseptic prosthetic loosening in TJA. Daphnetin (DAP), a natural coumarin derivative, is clinically used in Traditional Chinese Medicine for the treatment of rheumatoid arthritis due to its anti‐inflammatory properties. In this study, we report for the first time that DAP could protect against lipopolysaccharide‐induced inflammatory bone destruction in a murine calvarial osteolysis model in vivo. This protective effect of DAP can in part be attributed to its direct inhibitory effect on RANKL‐induced osteoclast differentiation, fusion, and bone resorption in vitro. Biochemical analysis found that DAP inhibited the activation of the ERK and NFATc1 signaling cascades. Collectively, our findings suggest that DAP as a natural compound has potential for the treatment of inflammatory osteolysis.
Novel One‐Pot Synthesis of Functionalized Quinolines from Isocyanides, Aniline, and Acetylene Dicarboxylate via Cu‐Catalyzed Intramolecular C─H Activation Reactions
Authors: Nematpour Manijeh , Rezaee Elham , Jahani Mehdi , Tabatabai Sayyed Abbas
Published: February 2019

The one‐pot synthesis of a novel class of substituted quinoline derivatives with good yields is achieved via the Cu‐catalyzed intramolecular C─H activation reaction between isocyanides, aniline, and acetylene dicarboxylate in MeCN at room temperature. The existence of one‐pot conditions, availability of a starting material‐catalyst, the absence of column chromatography, and a high yield of products are among the advantages of this method. The structures are confirmed spectroscopically (1H NMR and 13C NMR, IR, and EI‐MS) and through elemental analyses.
Allogeneic hematopoietic cell transplantation in Farber disease
Authors: Ehlert Karoline , Levade Thierry , Di Rocco Maja , Lanino Edoardo , Albert Michael H. , Führer Monika , Jarisch Andrea , Güngör Tayfun , Ayuk Francis , Vormoor Josef
Published: February 2019

Background

Farber disease (FD) is a rare, lysosomal storage disorder caused by deficient acid ceramidase activity. FD has long been considered a fatal disorder with death in the first three decades of life resulting either from respiratory insufficiency as a consequence of airway involvement or from progressive neurodegeneration because of nervous system involvement. Peripheral symptoms associated with FD, including inflammatory joint disease, have been described to improve relatively rapidly after hematopoietic cell transplantation (HCT).

Aims

To evaluate the disease‐specific status and limitations in the long‐term follow‐up after HCT, investigate genotype/phenotype correlations and the benefit of allogeneic HCT in FD patients with nervous system involvement.

Patients and methods

Transplant‐ and disease‐related information of ten FD patients was obtained by using a questionnaire, physicians' letters and additional telephone surveys. ASAH1 gene mutations were identified to search for genotype/phenotype correlations.

Results

After mainly busulfan‐based preparative regimens, all patients engrafted with one late graft loss. The inflammatory symptoms resolved completely in all patients. Abnormal neurologic findings were present pre‐transplant in 4/10 patients, post‐transplant in 6/10 patients. Mutational analyses revealed new mutations in the ASAH1 gene and a broad diversity of phenotypes without a genotype/phenotype correlation. With a median follow‐up of 10.4 years, overall survival was 80% with two transplant‐related deaths.

Conclusion

Allogeneic HCT leads to complete and persistent resolution of the inflammatory aspects in FD patients. It appears to have no beneficial effect on progression of nervous system involvement. New mutations in the acid ceramidase gene were identified. A genotype/phenotype correlation could not be established.
Human adenovirus replication and persistence in hypertrophic adenoids and palatine tonsils in children
Authors: Proenca‐Modena José Luiz , de Souza Cardoso Ricardo , Criado Miriã Ferreira , Milanez Guilherme Paier , de Souza William Marciel , Parise Pierina Lorencini , Bertol Jéssica Wildgrube , de Jesus Bruna Lais Santos , Prates Mirela Cristina Moreira , Silva Maria Lúcia , Buzatto Guilherme Pietrucci , Demarco Ricardo Cassiano , Valera Fabiana Cardoso Pereira , Tamashiro Edwin , Anselmo‐Lima Wilma Terezinha , Arruda Eurico
Published: February 2019

The role of human adenovirus (HAdV) infection in different acute diseases, such as febrile exudative tonsillitis, conjunctivitis, and pharyngoconjunctival fever is well established. However, the relationships, if any, of HAdV persistence and reactivation in the development of the chronic adenotonsillar disease is not fully understood. The present paper reports a 3‐year cross‐sectional hospital‐based study aimed at detecting and quantifying HAdV DNA and mRNA of the HAdV hexon gene in adenoid and palatine tonsil tissues and nasopharyngeal secretions (NPS) from patients with adenotonsillar hypertrophy or recurrent adenotonsillitis. HAdV C, B, and E were detectable in nearly 50% of the patients, with no association with the severity of airway obstruction, nor with the presence of recurrent tonsillitis, sleep apnea or otitis media with effusion (OME). Despite the higher rates of respiratory viral coinfections in patients with HAdV, the presence of other viruses, including DNA and RNA viruses, had no association with HAdV replication or shedding in secretions. Higher HAdV loads in adenoids showed a significant positive correlation with the presence of sleep apnea and the absence of OME. Although this study indicates that a significant proportion (~85%) of individuals with chronic adenotonsillar diseases have persistent nonproductive HAdV infection, including those by HAdV C, B, and E, epithelial and subepithelial cells in tonsils seem to be critical for HAdV C production and shedding in NPS in some patients, since viral antigen was detected in these regions by immunohistochemistry in four patients, all of which were also positive for HAdV mRNA detection.
A novel diffraction tomographic algorithm with narrow observation angle
Authors: Yang Chunxia , Zhang Jian , Tong Meisong
Published: February 2019

Conventional diffraction tomography (DT) can be used to reconstruct objects with 360° coverage of observation angle. But solving inverse problem could be challenging when the full angle data are not available. In this paper, a novel diffraction tomographic algorithm with extrapolation method is proposed to detect two‐dimensional (2D) dielectric objects in cases where the observation stations are far away from the search domain and the observation angles are limited to a narrow range. Extrapolation is introduced to obtain more data in the frequency domain. Using this algorithm, all locations, shapes, and dielectric properties of targets can be reconstructed under 90° or even narrower observation angle. Due to the use of fast Fourier transform in the implementation, this algorithm is very fast although many iterations of extrapolation are needed. Images can be reconstructed with nearly real‐time performance. Simulation results are given to show the validity of the algorithm.
Optimising proliferation and migration of mesenchymal stem cells using platelet products: A rational approach to bone regeneration
Authors: Moisley Katrina M. , El‐Jawhari Jehan J. , Owston Heather , Tronci Giuseppe , Russell Stephen J. , Jones Elena A. , Giannoudis Peter V.
Published: February 2019

This study investigates how mesenchymal stem cell's (MSCs) proliferation and migration abilities are influenced by various platelet products (PP). Donor‐matched, clinical‐, and control laboratory‐standard PPs were generated and assessed based on their platelet and leukocyte concentrations. Bone marrow derived MSCs were exposed to these PP to quantify their effect on in vitro MSC proliferation and migration. An adapted colony forming unit fibroblast (CFU‐F) assay was carried out on bone marrow aspirate using clinical‐standard PP‐loaded electrospun poly(ϵ‐caprolactone) (PCL) membrane to mimic future clinical applications to contain bone defects. Clinical‐standard PP had lower platelet (2.5 fold, p < 0.0001) and higher leukocyte (14.1 fold, p < 0.0001) concentrations compared to laboratory‐standard PP. It induced suboptimal MSC proliferation compared to laboratory‐standard PP and fetal calf serum (FCS). All PP induced significantly more MSC migration than FCS up to 24 h. The removal of leukocytes from PP had no effect on MSC proliferation or migration. The PP‐loaded membranes successfully supported MSC colony formation. This study indicates that platelet concentrations in PP impact MSC proliferation more than the presence of leukocytes, whilst MSC migration in response to PP is not influenced by platelet or leukocyte numbers. Clinical‐standard PP could be applied alongside manufactured membranes in the future treatment of bone reconstruction. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:1329–1338, 2019.
Parenteral Provision of Micronutrients to Adult Patients: An Expert Consensus Paper
Authors: Blaauw Renée , Osland Emma , Sriram Krishnan , Ali Azmat , Allard Johane P. , Ball Patrick , Chan Lingtak‐Neander , Jurewitsch Brian , Logan Coughlin Kathleen , Manzanares William , Menéndez Ana Maria , Mutiara Rina , Rosenfeld Ricardo , Sioson Marianna , Visser Janicke , Berger Mette M.
Published: February 2019

Background

Micronutrients, an umbrella term used to collectively describe vitamins and trace elements, are essential components of nutrition. Those requiring alternative forms of nutrition support are dependent on the prescribed nutrition regimen for their micronutrient provision. The purpose of this paper is to assist clinicians to bridge the gap between the available guidelines’ recommendations and their practical application in the provision of micronutrients via the parenteral route to adult patients.

Methods

Based on the available evidenced‐based literature and existing guidelines, a panel of multidisciplinary healthcare professionals with significant experience in the provision of parenteral nutrition (PN) and intravenous micronutrients developed this international consensus paper.

Results

The paper addresses 14 clinically relevant questions regarding the importance and use of micronutrients in various clinical conditions. Practical orientation on how micronutrients should be prescribed, administered, and monitored is provided.

Conclusion

Micronutrients are a critical component to nutrition provision and PN provided without them pose a considerable risk to nutrition status. Obstacles to their daily provision—including voluntary omission, partial provision, and supply issues—must be overcome to allow safe and responsible nutrition practice.
Interspecific competition changes nutrient : nutrient ratios of weeds and maize
Authors: da Conceição de Matos Christiano , da Silva Teixeira Rafael , da Silva Ivo Ribeiro , Costa Maurício Dutra , da Silva Antonio Alberto
Published: February 2019

The elemental ratios of plant tissues are associated with the adaptive and competitive success of a plant species in an ecosystem. So far, no study has evaluated if and how crop–weed competition influences the elemental ratios of competing populations, although such information is important to understand weed infestation dynamics and to improve weed management in agroecosystems. The objective of this study was to analyze weed–crop elemental ratios during interspecific competition between weeds and crops in greenhouse experiments. For this, maize (Zea mays L.) and the weeds Amaranthus viridis L, Bidens pilosa L., and Ipomoea grandifolia (Dammer) O'Donell were grown under seven treatments: maize and weed monocultures, and maize in competition with weeds. Competition between plants practically did not influence growth and nutrient contents of maize but reduced weed growth and nutrient uptake. Maize showed few changes in elemental ratios. In contrast, B. pilosa and I. grandifolia were very sensitive to competition and showed significant increases in C : N, C : P, C : K, N : P, and N : K ratios when grown with maize. A. viridis showed low flexibility of nutrient : nutrient ratios under the same competitive pressure as that faced by B. pilosa and I. grandifolia. The interspecific competition led to increases only in the C : P ratio of A. viridis shoots. Therefore, interspecific competition changes the elemental ratios, mainly of the weeds, and the magnitude of this change is dependent on the plant species involved. Interspecific competition changes plant biomass quality (higher C : nutrient ratios), mainly for B. pilosa and I. grandifolia.
Dry matter production, nutrient accumulation, and nutrient partitioning of barley
Authors: Rogers Christopher W. , Dari Biswanath , Hu Gongshe , Mikkelsen Robert
Published: February 2019

Total dry matter (TDM) and nutrient accumulation, nutrient partitioning, and cumulative growing degree days at the time of maximum nutrient accumulation for two‐row spring barley (Hordeum vulgare L.) are not well quantified under high‐yielding irrigated conditions common in the semi‐arid western United States. Thus, five cultivars of barley were grown under irrigated conditions on a loam soil in the 2015 and 2016 growth seasons to determine these factors. Total nutrient accumulation was greatest at either the soft dough or maturity stage where specific nutrients were greater at one stage as compared to the other. Mean N accumulation was greatest at the soft dough stage (256 kg ha−1) where the regression model accounted for 80% of the variation in the data. Additionally, spike N increased from 91 to 105 kg ha−1 from soft dough to maturity. Specific nutrients (e.g., K) had significantly greater plant (i.e., culms plus leaves) accumulation between soft dough and maturity, 253 and 172 kg ha−1, respectively, where the spike at the same growth stages had an accumulation of 37 and 42 kg ha−1, respectively. In contrast, other nutrients (e.g., P) were remobilized to the spike as noted by the increase from 14 kg ha−1 at soft dough to 26 kg ha−1 at maturity. In addition to nutrient partitioning, linear regressions resulted in well‐correlated models between TDM and total nutrient accumulation (R2 = 0.35–0.88) for measured nutrients. Results from the current study provide critical data on nutrient accumulation as well as regression models for two‐row barley under high‐yielding conditions. This information can be used to improve harvest decisions as well as more accurately predict nutrient cycling in barley cropping systems.