bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of significant gene and pathways involved in HBV-related hepatocellular carcinoma by bioinformatics analysis
Authors: Xie Shucai , Jiang Xili , Zhang Jianquan , Xie Shaowei , Hua Yongyong , Wang Rui , Yang Yijun
Published: July 2019

Background

Hepatocellular carcinoma (HCC) is a common malignant tumor affecting the digestive system and causes serious financial burden worldwide. Hepatitis B virus (HBV) is the main causative agent of HCC in China. The present study aimed to investigate the potential mechanisms underlying HBV-related HCC and to identify core biomarkers by integrated bioinformatics analyses.

Methods

In the present study, HBV-related HCC GSE19665, GSE55092, GSE94660 and GSE121248 expression profiles were downloaded from the Gene Expression Omnibus database. These databases contain data for 299 samples, including 145 HBV-related HCC tissues and 154 non-cancerous tissues (from patients with chronic hepatitis B). The differentially expressed genes (DEGs) from each dataset were integrated and analyzed using the RobustRankAggreg (RRA) method and R software, and the integrated DEGs were identified. Subsequently, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID online tool, and the protein–protein interaction (PPI) network was constructed using STRING and visualized using Cytoscape software. Finally, hub genes were identified, and the cBioPortal online platform was used to analyze the association between the expression of hub genes and prognosis in HCC.

Results

First, 341 DEGs (117 upregulated and 224 downregulated) were identified from the four datasets. Next, GO analysis showed that the upregulated genes were mainly involved in cell cycle, mitotic spindle, and adenosine triphosphate binding. The majority of the downregulated genes were involved in oxidation reduction, extracellular region, and electron carrier activity. Signaling pathway analysis showed that the integrated DEGs shared common pathways in retinol metabolism, drug metabolism, tryptophan metabolism, caffeine metabolism, and metabolism of xenobiotics by cytochrome P450. The integrated DEG PPI network complex comprised 288 nodes, and two important modules with high degree were detected using the MCODE plug-in. The top ten hub genes identified from the PPI network were SHCBP1, FOXM1, KIF4A, ANLN, KIF15, KIF18A, FANCI, NEK2, ECT2, and RAD51AP1. Finally, survival analysis revealed that patients with HCC showing altered ANLN and KIF18A expression profiles showed worse disease-free survival. Nonetheless, patients with FOXM1, NEK2, RAD51AP1, ANLN, and KIF18A alterations showed worse overall survival.

Conclusions

The present study identified key genes and pathways involved in HBV-related HCC, which improved our understanding of the mechanisms underlying the development and recurrence of HCC and identified candidate targets for the diagnosis and treatment of HBV-related HCC.
Physico-chemical, Gas Chromatography-Mass Spectrometry (GC-MS) Analysis and Cold Saponification of Wild Grapes (Lannea microcarpa Engl & K. Krause) Seed Oil
Authors: Warra Aliyu Ahmad , Mohammed Hadiza Ibrahim , Morayo Adejuwon Olorunsola
Published: July 2019

Aims: Physico-chemical, Gas Chromatography-Mass Spectrometry (GC-MS) and Cold saponification was carried out on Lannea microcarpa (Wild grape) seed oil with the aim of identifying the quality and quantity of the oil and its suitability in soap production.

Study Design: Experimental and instrumental study was done to determine the physicochemical characteristics, fatty acids present in the seed oil and its suitability for soap production.

Place and Duration of Study: The study was conducted at the Biochemistry Laboratory, Kebbi State University of Science and Technology, Aliero, Nigeria from May to June, 2014.

Methodology: The hexane extract of the sample was obtained by complete extraction using Soxhlet extractor, physicochemical analysis was carried out. A gas chromatography coupled with mass spectroscopy detector (GC-MS) system was used for the qualitative fatty acid determination. Simple cold method saponification was used in producing the soap.

Results: The powdered seed (50 g) yielded 59.21±0.01% of the oil. Results from the physicochemical analysis showed the seed oil to be dark purple in colour and partially soluble in water with the acid, iodine, saponification and peroxide values at  16± 0.01 mgKOH/g, 121.6±0.1 gI2/100 g, 231.25±0.02 mgKOH/g,  3.02±0.01 meq H2O2respectively. The relative density and refractive index of the oil are at 0.5983±0.0001 (g/cm3) and 1.43±0.01 respectively. Qualitative GC-MS revealed the following fatty acids; Decanoic acid, Palmitic acid, Stearic acid, Margaric acid, 1-octadecanoic  acid, Oleic and Erucic acid. The soap produced from the seed oil has pH and Foam height, 10.18±0.01 and 105.1±0.1 (cm³) respectively.

Conclusion: The present study on seeds of wild grape revealed that the oil is a viable natural product that can be utilized in thefood and cosmetic industry.
Growth and Extracellular Enzyme Activity Responses of a Multi-enzymic Strain of Serratia sp. in a Simulated Diesel-contaminated System
Authors: Asitok Atim , Antai Sylvester , Ekpenyong Maurice
Published: July 2019

Aim: The present study was aimed at elucidating the alternative metabolic preferences of Serratia sp. strain DW2 that permitted its survival in a diesel-contaminated environment.

Study Design: We adopted a 4 x 4 x 3 completely randomized design of a full-factorial experiment for the study.

Place and Duration of Study: The study was conducted at the Department of Microbiology, University of Calabar, Nigeria, during the months of March and June, 2019.

Methodology: In this study, Serratia sp. strain DW2 was isolated from Douglas Creek water of the Qua Iboe Estuary, along the Qua Iboe terminal at Ibeno, Nigeria, as a significant biological contributor to the decontamination process through inherent ability to utilize diesel oil hydrocarbons. This paper elucidated the growth and responses of the bacterial lipase, caseinase and gelatinase activities to diesel-oil hydrocarbon contamination.

Results: Range finding test results showed that the bacterium could grow in the presence of water soluble fraction of diesel (wsf-D) concentration between .0042 and .0335 µg/mL, albeit with increasing lag time and decreasing specific growth rate when compared with growth in glucose-Bushnell-Haas broth. Lag time changes were not significantly influenced by exposure time but changes in specific growth rate were. Gelatinase activity was most susceptible to toxicant onslaught but was least affected by exposure time. Conversely, lipase activity was the most affected by exposure time. Toxicant concentration/exposure time interaction of a two-way analysis of variance model for caseinase activity was not significant (P > .05) but those for lipase and gelatinase activities were.

Conclusion: The bacterium survived diesel toxicity by exploiting its lipase and gelatinase activities for provision of alternative sources of carbon, energy and nitrogen to drive ecosystem decontamination in the event of refined petroleum contamination.
RAS and BRAF mutations in cell‐free DNA are predictive for outcome of cetuximab monotherapy in patients with tissue‐tested RAS wild‐type advanced colorectal cancer
Authors: van Helden Erik J. , Angus Lindsay , Menke‐van der Houven van Oordt C. Willemien , Heideman Daniëlle A. M. , Boon Eline , van Es Suzanne C. , Radema Sandra A. , van Herpen Carla M. L. , de Groot Derk Jan A. , de Vries Elisabeth G. E. , Jansen Maurice P. H. M. , Sleijfer Stefan , Verheul Henk M. W.
Published: July 2019

In metastatic colorectal cancer, RAS and BRAF mutations cause resistance to anti‐EGFR therapies, such as cetuximab. Heterogeneity in RAS and BRAF mutations might explain nonresponse in a subset of patients receiving cetuximab. Analyzing mutations in plasma‐derived circulating tumor DNA (ctDNA) could provide a more comprehensive overview of the mutational landscape as compared to analyses of primary and/or metastatic tumor tissue. Therefore, this prospective multicenter study followed 34 patients with metastatic colorectal cancer who were tissue‐tested as RAS wild‐type (exons 2–4) during routine work‐up and received third‐line cetuximab monotherapy. BRAF mutation status was also tested but did not exclude patients from therapy. At baseline and upon disease progression, cell‐free DNA (cfDNA) was isolated for targeted next‐generation sequencing (NGS). At 8 weeks, we determined that patients had benefited from treatment. NGS of cfDNA identified three patients with RAS mutations not detected in tumor tissue during routine work‐up. Another six patients had a BRAF or rare RAS mutation in ctDNA and/or tumor tissue. Relative to patients without mutations in RAS/BRAF, patients with mutations at baseline had shorter progression‐free survival [1.8 versus 4.9 months (P < 0.001)] and overall survival [3.1 versus 9.4 months (P = 0.001)]. In patients with clinical benefit (progressive disease after 8 weeks), ctDNA testing revealed previously undetected mutations in RAS/BRAF (71%) and EGFR (47%), which often emerged polyclonally. Our results indicate that baseline NGS of ctDNA can identify additional RAS mutation carriers, which could improve patient selection for anti‐EGFR therapies. Acquired resistance, in patients with initial treatment benefit, is mainly explained by polyclonal emergence of RAS, BRAF, and EGFR mutations in ctDNA.
Proximity labeling to detect RNA–protein interactions in live cells
Authors: Lu Mingxing , Wei Wencheng
Published: July 2019

RNA biology is orchestrated by the dynamic interactions of RNAs and RNA‐binding proteins (RBPs). In the present study, we describe a new method of proximity‐dependent protein labeling to detect RNA–protein interactions [RNA‐bound protein proximity labeling (RBPL)]. We selected the well‐studied RNA‐binding protein PUF to examine the current proximity labeling enzymes birA* and APEX2. A new version of birA*, BASU, was used to validate that the PUF protein binds its RNA motif. We further optimized the RBPL labeling system using an inducible expression system. The RBPL (λN‐BASU) labeling experiments exhibited high signal‐to‐noise ratios. We subsequently determined that RBPL (λN‐BASU) is more suitable than RBPL (λN‐APEX2) for the detection of RNA–protein interactions in live cells. Interestingly, our results also reveal that proximity labeling is probably capable of biotinylating proximate nascent peptide.
Factors Associated With Participation in Rheumatic Disease–Related Research Among Underrepresented Populations: A Qualitative Systematic Review
Authors: Lima Kaitlin , Phillip Courtnie R. , Williams Jessica , Peterson Jonna , Feldman Candace H. , Ramsey-Goldman Rosalind
Published: July 2019

Objective

Nonwhite racial/ethnic groups remain underrepresented in rheumatic disease–related research, despite being disproportionately affected by these disorders. Our objective was to systematically review the literature regarding underrepresented patients’ perceptions of participation in rheumatic disease research and to develop strategies to improve diversity.

Methods

A systematic search of Embase, PubMed/Medline, PsycINFO, and Cochrane was performed through October 2018. Two independent reviewers identified 642 unique studies; 7 met inclusion criteria (peer‐reviewed articles, published in English in the last 20 years, adult population, and with a focus on underrepresented patients’ participation in rheumatic research). Five coauthors provided final approval of included articles. Data abstraction was performed, and common themes and key differences were determined and adjudicated.

Results

The 7 articles included (n = 1,892 patients, range per article 20–961) evaluated factors associated with research participation of underrepresented populations. Five articles were related to lupus and 2 to rheumatoid arthritis, and 5 focused on African American patients and 1 on Hispanic patients. Five of the studies provided quantitative data through surveys (n = 3) and chart review (n = 2), while 2 used qualitative analyses. Key themes regarding underrepresented patients’ perceptions of participating in research included: 1) the importance of trust in the patient– physician relationship, 2) the understanding of heterogeneity within and between ethnic groups, 3) the need for authentic academic‐community partnerships, and 4) the implications of strict inclusion criteria on study participant diversity.

Conclusion

Limited evidence exists regarding underrepresented patients’ attitudes toward research participation in rheumatology, and further investigation is warranted. The themes identified provide a starting point for future interventions that promote increased diversity in rheumatic disease–related research studies.
Toward 3D‐Printed Electronics: Inkjet‐Printed Vertical Metal Wire Interconnects and Screen‐Printed Batteries
Authors: Sowade Enrico , Polomoshnov Maxim , Willert Andreas , Baumann Reinhard R.
Published: July 2019

Inkjet and screen printing technologies are well known in the graphic arts industry for the reproduction of texts, images, and graphics. During the last decades, these printing technologies have been attracting increasing interest for the deposition of functional materials, e.g., in the field of printed electronics and for biological applications. However, their usage is mainly limited to 2D applications, i.e., rather flat deposits ranging from nanometers to several tens of micrometers in thickness. For 3D applications, sophisticated additive manufacturing technologies are developed to manufacture structures with high shape complexities. Herein, the potential of standard inkjet and screen printing technology as tools for the development of functional 3D objects is demonstrated. 3D functional structures printed by inkjet and screen printing technology combining conductive and nonconductive materials to a multi‐material structure are shown. A metal nanoparticle ink formulation is applied to inkjet‐print conductive metal pillars with a high aspect ratio (in the range of 50) used as vertical interconnects. The interconnects are encapsulated with an inkjet‐printed polymeric ink formulation and finally used as conductive tracks to light up a solid‐state light‐emitting diode (LED). Screen printing is applied to print primary batteries used as the power source for the LED.
Muscle and joint function in children living with arthrogryposis multiplex congenita: A scoping review
Authors: Gagnon Marianne , Caporuscio Kevin , Veilleux Louis‐Nicolas , Hamdy Reggie , Dahan‐Oliel Noémi
Published: July 2019

Arthrogryposis multiplex congenita (AMC) is characterized by congenital joint contractures present in two or more body areas. Lack of fetal movement is the underlying cause of AMC, which can lead to abnormal connective tissue surrounding the joint resulting in stiffness and muscle atrophy. Treatment aims at improving function and mobility through surgical and/or conservative interventions. A scoping review was conducted to explore the existing knowledge of the evaluation and treatment of muscle and joint function in children with AMC. Three search engines were included and identified 1,271 articles. Eighty‐seven studies met the selection criteria and were included in this review. All included studies focused on joints, 30 of which also assessed the muscle. Assessment most often included the position of the contractures (n = 72), as well as range of motion (n = 66). Interventions to improve muscle and joint function were reported in 82 of the 87 papers and included surgery (n = 70) and conservative interventions (n = 74) with bony surgery (i.e., osteotomy) the most common surgery and rehabilitation the most common conservative intervention. Recurrences of contractures were mentioned in 46 of the 68 studies providing a follow‐up. Future studies should use validated measures to assess muscle and joint function, and conservative interventions should be described in greater detail and to include a longer follow‐up.
Observation of the Low‐Frequency Spectrum of the Water Dimer as a Sensitive Test of the Water Dimer Potential and Dipole Moment Surfaces
Authors: Schwan Raffael , Qu Chen , Mani Devendra , Pal Nitish , van der Meer Lex , Redlich Britta , Leforestier Claude , Bowman Joel M. , Schwaab Gerhard , Havenith Martina
Published: July 2019

Using the helium nanodroplet isolation setup at the ultrabright free‐electron laser source FELIX in Nijmegen (BoHeNDI@FELIX), the intermolecular modes of water dimer in the frequency region from 70 to 550 cm−1 were recorded. Observed bands were assigned to donor torsion, acceptor wag, acceptor twist, intermolecular stretch, donor torsion overtone, and in‐plane and out‐of‐plane librational modes. This experimental data set provides a sensitive test for state‐of‐the‐art water potentials and dipole moment surfaces. Theoretical calculations of the IR spectrum are presented using high‐level quantum and approximate quasiclassical molecular dynamics approaches. These calculations use the full‐dimensional ab initio WHHB potential and dipole moment surfaces. Based on the experimental data, a considerable increase of the acceptor switch and a bifurcation tunneling splitting in the librational mode is deduced, which is a consequence of the effective decrease in the tunneling barrier.
Copper‐Catalyzed Asymmetric Annulation Reactions of Carbenes with 2‐Iminyl‐ or 2‐Acyl‐Substituted Phenols: Convenient Access to Enantioenriched 2,3‐Dihydrobenzofurans
Authors: Liang Xin‐Shen , Li Rui‐Dong , Wang Xiao‐Chen
Published: July 2019

We have developed a method for the highly diastereo‐ and enantioselective construction of 2,3‐dihydrobenzofurans bearing tetrasubstituted carbon stereocenters by means of annulation reactions between carbenes and 2‐iminyl‐ or 2‐acyl‐substituted phenols through catalysis by readily accessible copper(I)/bisoxazoline catalysts under mild conditions. These reactions feature a unique mechanism in which the copper catalyst serves a dual function: first it reacts with the diazo compound to generate a metal carbene, and second, upon formation of an oxonium ylide, it acts as a Lewis acid to activate the imine or ketone for diastereo‐ and enantioselective cyclization.
Kontrolle über Selbstassemblierung durch Ausnutzung von Koordinationsisomerie
Authors: Bäumer Nils , Kartha Kalathil K. , Allampally Naveen Kumar , Yagai Shiki , Albuquerque Rodrigo Q. , Fernández Gustavo
Published: July 2019

Hierin wird die inhärente geometrische Isomerie eines PtIIKomplexes als neues Werkzeug zur Kontrolle von supramolekularen Assemblierungsprozessen ausgenutzt. Bestrahlung mit UV‐Licht sowie die sorgfältige Auswahl des verwendeten Lösungsmittels, der Temperatur und Konzentration führen zu einer regelbaren Koordinationsisomerie. Dies ermöglicht ein vollständig reversibles Schalten zwischen zwei definierten aggregierten Spezies (1D Fasern ↔ 2D Lamellen) mit unterschiedlichem photoresponsivem Verhalten. Unsere Erkenntnisse erweitern nicht nur die Reichweite von Koordinationsisomerie, sondern eröffnen auch aufregende Möglichkeiten zur Entwicklung neuartiger stimuliresponsiver Materialien.
A μ‐Phosphido Diiron Dumbbell in Multiple Oxidation States
Authors: Ghosh Munmun , Cramer Hanna H. , Dechert Sebastian , Demeshko Serhiy , John Michael , Hansmann Max M. , Ye Shengfa , Meyer Franc
Published: July 2019

The reaction of the ferrous complex [LFe(NCMe)2](OTf)2 (1), which contains a macrocyclic tetracarbene as ligand (L), with Na(OCP) generates the OCP−‐ligated complex [LFe(PCO)(CO)]OTf (2) together with the dinuclear μ‐phosphido complex [(LFe)2P](OTf)3 (3), which features an unprecedented linear Fe‐(μ‐P)‐Fe motif and a “naked” P‐atom bridge that appears at δ=+1480 ppm in the 31P NMR spectrum. 3 exhibits rich redox chemistry, and both the singly and doubly oxidized species 4 and 5 could be isolated and fully characterized. X‐ray crystallography, spectroscopic studies, in combination with DFT computations provide a comprehensive electronic structure description and show that the Fe‐(μ‐P)‐Fe core is highly covalent and structurally invariant over the series of oxidation states that are formally described as ranging from FeIIIFeIII to FeIVFeIV. 3–5 now add a higher homologue set of complexes to the many systems with Fe‐(μ‐O)‐Fe and Fe‐(μ‐N)‐Fe core structures that are prominent in bioinorganic chemistry and catalysis.
Microenvironment Engineering of Ruthenium Nanoparticles Incorporated into Silica Nanoreactors for Enhanced Hydrogenations
Authors: Ren Xiaomin , Guo Miao , Li He , Li Chengbin , Yu Liang , Liu Jian , Yang Qihua
Published: July 2019

It is a challenging task to promote the activity and selectivity of a catalyst via precisely engineering the microenvironment, an important factor related with the catalytic performance of natural catalysts. Motivated by the water effect in promoting the catalytic activity explored in this work, a nanoreactor modified with phosphine ligand enabled the efficient hydrogenation of benzoic acid (BA) over Ru nanoparticles (NPs) in organic solvent under mild conditions, which cannot be achieved in unmodified nanoreactors. Both density functional theory (DFT) calculations and catalytic performance tests showed that the phosphine ligands can manipulate the adsorption strength of BA on Ru NPs by tuning the surface properties as well as preferentially interacting with the carboxyl of BA. The insights obtained in the present study provide a novel concept of nanoreactor design by anchoring ligands near catalytically active centers.
Exploiting Coordination Isomerism for Controlled Self‐Assembly
Authors: Bäumer Nils , Kartha Kalathil K. , Allampally Naveen Kumar , Yagai Shiki , Albuquerque Rodrigo Q. , Fernández Gustavo
Published: July 2019

We exploited the inherent geometrical isomerism of a PtIIcomplex as a new tool to control supramolecular assembly processes. UV irradiation and careful selection of solvent, temperature, and concentration leads to tunable coordination isomerism, which in turn allows fully reversible switching between two distinct aggregate species (1D fibers↔2D lamellae) with different photoresponsive behavior. Our findings not only broaden the scope of coordination isomerism, but also open up exciting possibilities for the development of novel stimuli‐responsive nanomaterials.
Biobased miktoarm star copolymer from soybean oil, isosorbide, and caprolactone
Authors: Teng Xiaoxu , Zhang Pei , Liu Tuan , Xin Junna , Zhang Jinwen
Published: July 2019

Soybean oil‐based macroinitiator was prepared from epoxidized soybean oil. A 1H NMR quantitative method was utilized for the characterization of this macroinitiator. A kind of renewable carbohydrate derivate, 1,4: 3,6‐Dianhydro‐D‐glucitol 2‐acrylate 5‐acetate (AAI) was prepared as the substitute monomer of styrene. Series of renewable miktoarm star copolymers initiated by soybean oil macroinitiator were obtained by atom transfer radical polymerization (ATRP) of AAI and ring‐opening polymerization (ROP) of ε‐caprolactone sequentially. The obtained miktoarm star block copolymers were characterized by 1H NMR, FTIR, and DSC. The DSC results show well dependence of the thermal behaviors of these miktoarm star block copolymers on the component of the two kinds of segments. A new strategy of renewable resource utilization has been provided on polymeric materials. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48281.
Amine‐impregnated natural zeolite as filler in mixed matrix membranes for CO2/CH4 separation
Authors: Castruita‐de León Griselda , Yeverino‐Miranda Claudia Y. , Montes‐Luna Angel de J. , Meléndez‐Ortiz Hector Iván , Alvarado‐Tenorio German , García‐Cerda Luis Alfonso
Published: July 2019

Flat mixed matrix membranes (MMMs) comprising polysulfone and clinoptilolite‐type natural zeolite were prepared by casting. Zeolite was modified with three alkylamines: ethanolamine (EA), bis(2‐hydroxypropyl)amine (BHPA), and polyethylenimine (PEI) by the impregnation method. Impregnated zeolite samples were characterized by X‐ray diffraction, Fourier transform infrared spectroscopy, and N2 adsorption–desorption. The alkylamine loading extent determined by thermogravimetric analysis was 5.2, 4.8, and 8.5% for EA, BHPA, and PEI, respectively. Analyses of MMMs showed that the incorporation of impregnated zeolite affected the glass‐transition temperature (Tg) and mixed‐gas transport properties. In this regard, a decreasing trend of the Tg values from 185.5 °C for the polymeric membrane up to 176.6 °C for Clino‐EA‐based MMM was recorded. In addition, the gas separation performance was evaluated at two different feed pressures. At 50 psi, MMMs showed an enhancement up to 30% on the CO2 permeability (22.79 Barrer) and 55% on the CO2/CH4 selectivity (45.78) in comparison with the polymeric membrane (CO2 permeability 17.34 Barrer; CO2/CH4 selectivity 29.38). These values varied depending on the alkylamine, BHPA being the most selective. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48286.
High‐efficiency preparation of polypropylene nanofiber by melt differential centrifugal electrospinning
Authors: Liu Yu‐Jian , Tan Jing , Yu Shao‐Yang , Yousefzadeh Maryam , Lyu Ting‐ting , Jiao Zhi‐Wei , Li Hao‐yi , Ramakrishna Seeram
Published: July 2019

Melt differential centrifugal electrospinning (MDCE) method is proposed by integrating the advantages of centrifugal spinning and melt differential electrospinning, including high efficiency, solvent‐free, multiple jets formation from nozzle‐less spinning system, and small diameter. A mathematical model of jet diameter in MDCE is established. An orthogonal experiment is carried out to explore the effects of main processing parameters on the average diameter and the diameter standard deviation of the prepared fibers. Ultimately, polypropylene (PP) nanofibers with an average diameter of 790 nm are successfully prepared in a higher flow rate of 124.26 g h−1 than that of other methods. The X‐ray diffraction and differential scanning calorimeter indicate that the introduction of high‐voltage electrostatic field in centrifugal spinning contribute to the crystal orientation of the PP molecular chain. Therefore, tensile mechanical strength is enhanced as the increase of the loading voltage. MDCE may provide an efficient and eco‐friendly method for nanofiber manufacturing in the future. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48299.
Dipeptidylpeptidase 4 as a Marker of Activated Fibroblasts and a Potential Target for the Treatment of Fibrosis in Systemic Sclerosis
Authors: Soare Alina , Györfi Hermina A. , Matei Alexandru E. , Dees Clara , Rauber Simon , Wohlfahrt Thomas , Chen Chih‐Wei , Ludolph Ingo , Horch Raymund E. , Bäuerle Tobias , von Hörsten Stephan , Mihai Carina , Distler Oliver , Ramming Andreas , Schett Georg , Distler Jörg H. W.
Published: July 2019

Objective

Expression of dipeptidylpeptidase 4 (DPP‐4) identifies a dermal fibroblast lineage involved in scarring during wound healing. The role of DDP‐4 in tissue fibrosis is, however, unknown. The aim of the present study was to evaluate DPP‐4 as a potential target for the treatment of fibrosis in patients with systemic sclerosis (SSc).

Methods

Expression of DPP‐4 in skin biopsy samples and dermal fibroblasts was analyzed by real‐time polymerase chain reaction, immunofluorescence, and Western blot analyses. The activity of DPP‐4 was modulated by overexpression, knockdown, and pharmacologic inhibition of DPP4 using sitagliptin and vildagliptin. The effects of DPP4 inhibition were analyzed in human dermal fibroblasts and in different mouse models of SSc (each n = 6).

Results

The expression of DPP‐4 and the number of DPP‐4–positive fibroblasts were increased in the fibrotic skin of SSc patients, in a transforming growth factor β (TGFβ)–dependent manner. DPP‐4–positive fibroblasts expressed higher levels of myofibroblast markers and collagen (each P < 0.001 versus healthy controls). Overexpression of DPP4 promoted fibroblast activation, whereas pharmacologic inhibition or genetic inactivation of DPP4 reduced the proliferation, migration, and expression of contractile proteins and release of collagen (each P < 0.001 versus control mice) by interfering with TGFβ‐induced ERK signaling. DPP4‐knockout mice were less sensitive to bleomycin‐induced dermal and pulmonary fibrosis (P < 0.0001 versus wild‐type controls). Treatment with DPP4 inhibitors promoted regression of fibrosis in mice that had received bleomycin challenge and mice with chronic graft‐versus‐host disease, and ameliorated fibrosis in TSK1 mice (each P < 0.001 versus untreated controls). These antifibrotic effects were associated with a reduction in inflammation.

Conclusion

DPP‐4 characterizes a population of activated fibroblasts and shows that DPP‐4 regulates TGFβ‐induced fibroblast activation in the fibrotic skin of SSc patients. Inhibition of DPP4 exerts potent antifibrotic effects when administered in well‐tolerated doses. As DPP4 inhibitors are already in clinical use for diabetes, these results may have direct translational implications for the treatment of fibrosis in patients with SSc.
Sepiapterin Reductase Inhibition Leading to Selective Reduction of Inflammatory Joint Pain in Mice and Increased Urinary Sepiapterin Levels in Humans and Mice
Authors: Fujita Masahide , Scheffer Débora da Luz , Turnes Bruna Lenfers , Cronin Shane J. F. , Latrémolière Alban , Costigan Michael , Woolf Clifford J. , Latini Alexandra , Andrews Nick A.
Published: July 2019

Objective

To evaluate the antiinflammatory and analgesic effects of sepiapterin reductase (SPR) inhibition in a mouse model of inflammatory joint disease, and to determine whether urinary sepiapterin levels, as measured in mice and healthy human volunteers, could be useful as a noninvasive, translational biomarker of SPR inhibition/target engagement.

Methods

The collagen antibody–induced arthritis (CAIA) model was used to induce joint inflammation in mice. The effects of pharmacologic inhibition of SPR on thresholds of heat‐, cold‐, and mechanical‐evoked pain sensitivity and on signs of inflammation were tested in mice with CAIA. In addition, mice and healthy human volunteers were treated with SPR inhibitors, and changes in urinary sepiapterin levels were analyzed by high‐performance liquid chromatography.

Results

CAIA in mice was characterized by 2 phases: in the acute inflammation (early) phase, joint inflammation and heat‐, mechanical‐, and cold‐induced pain hypersensitivity were present, while in the postinflammation (late) phase, no joint inflammation was observed but heat‐ and mechanical‐induced hypersensitivity, but not cold hypersensitivity, were present. Inhibition of SPR in mice with CAIA significantly attenuated the heat‐induced hyperalgesia in both phases, and the mechanical allodynia in the late phase. Signs of inflammation were unaffected by SPR inhibition. Urinary tetrahydrobiopterin levels, as a marker of inflammatory pain, were increased during inflammation in mice with CAIA (2‐fold increase over controls; P < 0.05) and significantly reduced by SPR inhibition (P < 0.05 versus vehicle‐treated mice). Increased urinary sepiapterin levels in the presence of SPR inhibition in both mice and healthy human volunteers were associated with high sensitivity (70–85%) and high specificity (82–88%) for the prediction of SPR inhibition/target engagement.

Conclusion

SPR inhibition reduces the pain associated with joint inflammation, thus showing its potential utility as an analgesic strategy for inflammatory joint pain. In addition, SPR inhibition increases urinary sepiapterin levels, indicating the potential of this measurement as a noninvasive biomarker of target engagement of SPR inhibitors, such as sulfasalazine, a disease‐modifying antirheumatic drug that is currently used as a first‐line treatment for rheumatoid arthritis.
Lichenicidin rational site‐directed mutagenesis library: A tool to generate bioengineered lantibiotics
Authors: Barbosa Joana , Caetano Tânia , Mösker Eva , Süssmuth Roderich , Mendo Sónia
Published: July 2019

Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that arise as an alternative to the traditional antibiotics. Lichenicidin is active against clinically relevant bacteria and it was the first lantibiotic to be fully produced in vivo in the Gram‐negative host Escherichia coli. Here, we present the results of a library of lichenicidin mutants, in which the mutations were generated based on the extensive bibliographical search available for other lantibiotics. The antibacterial activity of two‐peptide lantibiotics, as is lichenicidin, requires the synergistic activity of two peptides. We established a method that allows screening for bioactivity which does not require the purification of the complementary peptide. It is an inexpensive, fast and user‐friendly method that can be scaled up to screen large libraries of bioengineered two‐peptide lantibiotics. The applied system is reliable and robust because, in general, the results obtained corroborate structure–activity relationship studies carried out for other lantibiotics.
Reassessing the out‐of‐phase phenomenon in shake flasks by evaluating the angle‐dependent liquid distribution relative to the direction of the centrifugal acceleration
Authors: Azizan Amizon , Sieben Michaela , Wandrey Georg , Büchs Jochen
Published: July 2019

Shake flasks are still the most relevant experimental tool in the development of viscous fermentation processes. The phase number, which defines the onset of the unfavorable out‐of‐phase (OP) phenomenon in shake flasks, was previously defined via specific power input measurements. In the OP state, the bulk liquid no longer follows the orbital movement of the imposed centrifugal force, which is for example, detrimental to oxygen transfer. In this study, an optical fluorescence technique was used to measure the three‐dimensional liquid distribution in shake flasks. Four new optically derived evaluation criteria for the phase transition between the in‐phase and OP condition were established: (a) thickness of the liquid film left on the glass wall by the rotating bulk liquid, (b) relative slope of the leading edge of bulk liquid (LB) lines, (c) trend of the angular position of LB, and (d) very high angular position of the leading edge. In contrast to the previously applied power input measurements, the new optical evaluation criteria describe the phase transition in greater detailed. Instead of Ph = 1.26, a less conservative value of Ph = 0.91 is now suggested for the phase transfer, which implies a broader operating window for shake flask cultivations with higher viscosities.
A graph representation of functional diversity of brain regions
Authors: Yin Dazhi , Chen Xiaoyu , Zeljic Kristina , Zhan Yafeng , Shen Xiangyu , Yan Gang , Wang Zheng
Published: July 2019

Introduction

Modern network science techniques are popularly used to characterize the functional organization of the brain. A major challenge in network neuroscience is to understand how functional characteristics and topological architecture are related in the brain. Previous task‐based functional neuroimaging studies have uncovered a core set of brain regions (e.g., frontal and parietal) supporting diverse cognitive tasks. However, the graph representation of functional diversity of brain regions remains to be understood.

Methods

Here, we present a novel graph measure, the neighbor dispersion index, to test the hypothesis that the functional diversity of a brain region is embodied by the topological dissimilarity of its immediate neighbors in the large‐scale functional brain network.

Results

We consistently identified in two independent and publicly accessible resting‐state functional magnetic resonance imaging datasets that brain regions in the frontoparietal and salience networks showed higher neighbor dispersion index, whereas those in the visual, auditory, and sensorimotor networks showed lower neighbor dispersion index. Moreover, we observed that human fluid intelligence was associated with the neighbor dispersion index of dorsolateral prefrontal cortex, while no such association for the other metrics commonly used for characterizing network hubs was noticed even with an uncorrected p < .05.

Conclusions

This newly developed graph theoretical method offers fresh insight into the topological organization of functional brain networks and also sheds light on individual differences in human intelligence.
The prevalence, trends, and geographical distribution of human papillomavirus infection in China: The pooled analysis of 1.7 million women
Authors: Zhu Bo , Liu Yunyong , Zuo Tingting , Cui Xiaoli , Li Mengdan , Zhang Jing , Yu Huihui , Piao Haozhe
Published: July 2019

Human papillomavirus (HPV) infection which continues to be the most common sexually transmitted disease, has been identified as a major risk factor for cervical cancer. Therefore, it is very important to understand and grasp the distribution of HPV in Chinese population, and make the foundation for the development of cervical cancer vaccine in China. An extensive search strategy was conducted in multiple literature databases. All retrieved studies were screened by October 31, 2018. The prevalence of HPV infection was analyzed using random effects model. A total of 68 studies satisfied the inclusion criteria for our study. The national overall prevalence of HPV infection was 15.54% (95% CI: 13.83%‐17.24%). we also performed subgroup analysis by age, geographic location, level of economic development, HPV assay method, and type of HPV infection. The top 5 common HPV types detected in general population, were HPV 16 (3.52%, 95% CI: 3.18%‐3.86%), 52 (2.20%, 95% CI: 1.93%‐2.46%), 58 (2.10%, 95% CI: 1.88%‐2.32%), 18 (1.20%, 95% CI: 1.05%‐1.35%), and 33 (1.02%, 95% CI: 0.89%‐1.14%). Except for the higher prevalence of HPV infection in 2009 and 2010, the prevalence of HPV infection in other years changed little, ranged from 13.2% to 17.4%. HPV type in Chinese women was quite distinctive. HPV infection played a critical role in the occurrence of cervical cancer, understanding the distribution of HPV type and performing the HPV type testing had important clinical value for colposcopy referral and increasing the detection rate. Therefore, our findings could provide evidence for cervical cancer screening and vaccine, in order to reduce the burden of cervical cancer.
Incidence and outcome of BCR‐ABL mutated chronic myeloid leukemia patients who failed to tyrosine kinase inhibitors
Authors: Etienne Gabriel , Dulucq Stéphanie , Huguet Françoise , Schmitt Anna , Lascaux Axelle , Hayette Sandrine , Fort Marie‐Pierre , Sujobert Pierre , Bijou Fontanet , Morisset Stéphane , Tavitian Suzanne , Bidet Audrey , Turcq Beatrice , Robbesyn Fanny , Chollet Claudine , Belloc Francis , Durrieu Françoise , Mahon François‐Xavier , Nicolini Franck E.
Published: July 2019

Purpose

To assess the incidence of BCR‐ABL kinase domain (KD) mutation detection and its prognostic significance in chronic phase chronic myeloid leukemia (CP‐CML) patients treated with tyrosine kinase inhibitors (TKIs).

Patients and Methods

We analyzed characteristics and outcome of 253 CP‐CML patients who had at least one mutation analysis performed using direct sequencing. Of them, 187 patients were early CP (ECP) and 66 were late CP late chronic phase (LCP) and 88% were treated with Imatinib as first‐line TKI.

Results

Overall, 80 (32%) patients harbored BCR‐ABL KD mutations. A BCR‐ABL KD mutation was identified in 57% of patients, who progressed to accelerated or blastic phases (AP‐BP), and 47%, 29%, 35%, 16% and 26% in patients in CP‐CML at the time of mutation analysis who lost a complete hematologic response, failed to achieve or loss of a prior complete cytogenetic and major molecular response, respectively.

Overall survival and cumulative incidence of CML‐related death were significantly correlated with the disease phase whatever the absence or presence of a mutation was and for the latter the mutation subgroup (T315I vs P‐loop vs non‐T315I non‐P‐loop) (P<.001). Considering patients who were in CP at the time of mutation analysis, LCP mutated patients had a significantly worse outcome than ECP‐mutated patients despite a lower incidence of T315I and P‐loop mutations (P<.001). With a median follow‐up from mutation analysis to last follow‐up of 5 years, T315I and P‐loop mutations were not associated with a worse outcome in ECP patients (P = .817).

Conclusion

Our results suggest that early mutation detection together with accessibility to 2nd and 3rd generation TKIs have reversed the worst outcome associated with BCR‐ABL KD mutations whatever the mutation subgroup in CP‐CML patients.
Characterization of phenolic compound antioxidant activity in oat varieties using UHPLC–online ABTS and LC Q‐TOF
Authors: Rao Shiwangni , Santhakumar Abishek B. , Chinkwo Kenneth A. , Blanchard Christopher L.
Published: July 2019

Background and objectives

Phenolic compounds present in oats provide an opportunity for oats to increase its use in the form of functional food. In this study, eight varieties of Australian‐grown whole‐grain oat were investigated for their phenolic composition and antioxidant potential. Ultra‐high‐performance liquid chromatography–online 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid), coupled with liquid chromatography quadrupole time‐of‐flight, was used to identify and quantify individual phenolic compounds and their respective antioxidant activity.

Findings

Considerable variation in phenolic content (19.51 ± 1.20–52.49 ± 1.70 mg 100 g−1 GAE) and antioxidant activity was observed among the oat varieties. Several avenanthramides (AVNs) were detected with AVN A and AVN C being the most abundant. AVN C exhibited the highest antioxidant activity followed by caffeic acid, quercetin‐3,4′‐O‐di‐beta‐glucopyranoside derivative, and 6‐hydroxykaempferol 3,5,7,4′‐tetramethyl ether 6‐rhamnoside. Antioxidant activity in AVNs was observed to be the highest in AVN C followed by AVN B and AVN A.

Conclusions

High levels of AVN C and the range of phenolic compounds present show promise of Australian‐grown oats as an important source of antioxidant compounds. These antioxidant compounds may contribute to consumers' health benefits.

Significance and novelty

This study contributes to the use of oats as potential functional food by characterizing its individual phenolic compounds and their antioxidant activity.
Astonishing improvement of destructive mandibular osteomyelitis by NSAIDs: A rare lesion site in a patient with SAPHO syndrome
Authors: Tago Masaki , Katsuki Naoko E. , Motomura So , Tokushima Yoshinori , Yamashita Shu‐ichi
Published: July 2019

When patients develop destructive osteomyelitis, clinicians must always consider the possibility of SAPHO syndrome because even extremely destructive osteomyelitis can be cured by NSAIDs.
Direct Synthesis of Substituted (Z)‐Allylic Sulfones by Palladium‐Catalyzed Sulfonylation of Vinylethylene Carbonates with Sodium Sulfinates
Authors: Ke Miaolin , Huang Guanxin , Ding Li , Fang Jingjie , Chen Fen‐er
Published: July 2019

A palladium‐catalyzed highly stereoselective sulfonylation of vinylethylene carbonates for the precise synthesis of structurally diverse (Z)‐allylic sulfones was achieved with excellent regioselectivity and stereoselectivity (Z/E ratio, up to 99 : 1). This protocol used inexpensive sodium sulfinates as sulfonyl sources to construct valuable (Z)‐allylic sulfones in good to excellent yields. The controlling experiment suggested that the hydroxyl proton came from the α‐hydrogen of sulfone group through 1, 5‐H shift.
Electronic, Structural and Functional Versatility in Tetrathiafulvalene‐Lanthanide Metal–Organic Frameworks
Authors: Castells‐Gil Javier , Mañas‐Valero Samuel , Vitórica‐Yrezábal Iñigo J. , Ananias Duarte , Rocha João , Santiago Raul , Bromley Stefan T. , Baldoví José J. , Coronado Eugenio , Souto Manuel , Mínguez Espallargas Guillermo
Published: July 2019

Tetrathiafulvalene‐lanthanide (TTF‐Ln) metal–organic frameworks (MOFs) are an interesting class of multifunctional materials in which porosity can be combined with electronic properties such as electrical conductivity, redox activity, luminescence and magnetism. Herein a new family of isostructural TTF‐Ln MOFs is reported, denoted as MUV‐5(Ln) (Ln=Gd, Tb, Dy, Ho, Er), exhibiting semiconducting properties as a consequence of the short intermolecular S⋅⋅⋅S contacts established along the chain direction between partially oxidised TTF moieties. In addition, this family shows photoluminescence properties and single‐molecule magnetic behaviour, finding near‐infrared (NIR) photoluminescence in the Yb/Er derivative and slow relaxation of the magnetisation in the Dy and Er derivatives. As such properties are dependent on the electronic structure of the lanthanide ion, the immense structural, electronic and functional versatility of this class of materials is emphasised.
Effect of hydrogen addition on formation of hydrogen and carbon from methane decomposition over Ni/Al2O3
Authors: Wang Jiaofei , Jin Lijun , Yu Guangsuo , Hu Haoquan
Published: July 2019

The effects of hydrogen addition on the formation of hydrogen and carbon from methane decomposition over Ni/Al2O3 were studied. The results show that the added hydrogen in methane greatly affects the methane conversion, hydrogen output rate, and the properties of the carbon deposits on the surface of the Ni/Al2O3. The methane conversion and hydrogen output rate are significantly improved by the addition of hydrogen. As the flowrate of hydrogen increases from 0 to 25 mL/min, the initial activity of Ni/Al2O3 decreases sharply, while the stability increases first and then decreases due to the suppression of hydrogen to CH4 decomposition in the thermodynamics equilibrium. When the addition flowrate of the hydrogen is 15 mL/min, that is, 37.5% of the methane flowrate, a much higher methane conversion and the best stability of Ni/Al2O3 are obtained. The addition of a specific amount of hydrogen benefits the methane decomposition; however, the excessive hydrogen will suppress the decomposition. Most of the carbon that deposits on the surface of Ni/Al2O3 is filamentous carbon when hydrogen is added to the methane, however, encapsulated carbon is mainly produced when no hydrogen is added. In addition, the formation of encapsulated carbon, which deactivates the catalyst, is inhibited by the added hydrogen.
A Facile Preparation Strategy for TiO2 Spheres by Direct Hydrolysis
Authors: Xin Wuhong , Zhao Zengdian , Yang Xianhai , Cheng Yingzhi , Sun Fazhe , Feng Liu
Published: July 2019

We have developed a convenient and environmentally benign method for the fabrication of sub‐micron‐sized TiO2 spheres through direct hydrolysis, with the assistance of hollow detergent bubbles as template. The samples obtained at elevated temperatures are firstly characterized by X‐ray diffraction (XRD) and the corresponding photocatalytic activities are evaluated by measuring the photocatalytic oxidation of methyl orange (MO). The results reveal that relative crystallinity and crystallite size have mutual influence on photocatalytic property. Then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) are carried out to investigate the morphology. It can be concluded that hollow templates transform into solid TiO2 products without auxiliary additives. This strategy is quite promising for the low cost, no waste effluent and high productivity, providing a wide range of applications in photocatalysis, catalysis, solar‐cell, separation, and purification processes.