bluuebunny/crossref_metadata_2025 huggingface dataset:
A Chiral Polycyclic Aromatic Hydrocarbon Monkey Saddle
Authors: Kirschbaum Tobias , Rominger Frank , Mastalerz Michael
Published: October 2019

A contorted polycyclic aromatic hydrocarbon (PAH) in the shape of a monkey saddle has been synthesized in three steps from a readily available truxene precursor. The monkey saddle PAH is consisting of three five‐, seven six‐, and three eight‐membered rings and has been unambiguously characterized by single‐crystal X‐ray diffraction. Owing to the three biaryl axes the monkey saddle PAH is inherently chiral. The inversion of the two enantiomeric structures into each other preferably occurs through a twisting of peripheral rings rather than by a fully planar intermediate, as has been calculated by DFT methods. Enantiomers were separated by chiral HPLC and inversion barriers determined by variable temperature circular dichroism spectroscopy, supporting the twisting mechanism.
Rheumatoid Arthritis Morning Stiffness Is Associated With Synovial Fibrin and Neutrophils
Authors: Orange Dana E. , Blachere Nathalie E. , DiCarlo Edward F. , Mirza Serene , Pannellini Tania , Jiang Caroline S. , Frank Mayu O. , Parveen Salina , Figgie Mark P. , Gravallese Ellen M. , Bykerk Vivian P. , Orbai Ana‐Maria , Mackie Sarah L. , Goodman Susan M.
Published: October 2019

Objective

Morning stiffness is a hallmark symptom of rheumatoid arthritis (RA), but its etiology is poorly understood. This study was undertaken to determine whether any histologic features of synovium are associated with this symptom.

Methods

Data on patient‐reported morning stiffness duration and severity, and Disease Activity Score in 28 joints (DAS28) were collected from 176 patients with RA undergoing arthroplasty. Synovium was scored for 10 histopathologic features: synovial lining hyperplasia, lymphocytes, plasma cells, Russell bodies, binucleate plasma cells, fibrin, synovial giant cells, detritus, neutrophils, and mucin. Fibrinolysis of clots seeded with various cell types was measured in turbidimetric lysis assays.

Results

Stiffness severity and morning stiffness duration were both significantly associated with DAS28 (P = 0.0001 and P = 0.001, respectively). None of the synovial features examined were associated with patient‐reported stiffness severity. The presence of neutrophils and fibrin in RA synovial tissue were significantly associated (P < 0.0001) with patient‐reported morning stiffness of ≥1 hour, such that 73% of patients with both synovial fibrin and neutrophils reported morning stiffness of ≥1 hour. Further, neutrophils and fibrin deposits colocalized along the synovial lining. In in vitro analyses, fibrin clots seeded with necrotic neutrophils were more resistant to fibrinolysis than those seeded with living neutrophils or no cells (P = 0.008). DNase I treatment of necrotic neutrophils abrogated the delay in fibrinolysis.

Conclusion

In RA, prolonged morning stiffness may be related to impaired fibrinolysis of neutrophil‐enmeshed fibrin deposits along the synovial membrane. Our findings also suggest that morning stiffness severity and duration may reflect distinct pathophysiologic phenomena.
Ultrahigh‐cell‐density heterotrophic cultivation of the unicellular green microalga Scenedesmus acuminatus and application of the cells to photoautotrophic culture enhance biomass and lipid production
Authors: Jin Hu , Zhang Hu , Zhou Zhiwei , Li Kunpeng , Hou Guoli , Xu Quan , Chuai Wenhua , Zhang Chengwu , Han Danxiang , Hu Qiang
Published: October 2019

Although production of biodiesels from microalgae is proved to be technically feasible, a commercially viable system has yet to emerge. High‐cell‐density fermentation of microalgae can be coupled with photoautotrophic cultivation to produce oils. In this study, by optimizing culturing conditions and employing a sophisticated substrate feed control strategy, ultrahigh‐cell‐density of 286 and 283.5 g/L was achieved for the unicellular alga Scenedesmus acuminatus grown in 7.5‐L bench‐scale and 1,000‐L pilot‐scale fermenters, respectively. The outdoor scale‐up experiments indicated that heterotrophically grown S. acuminatus cells are more productive in terms of both biomass and lipid accumulation when they are inoculated in photobioreactors for lipid production as compared to the cells originally grown under photoautotrophic conditions. Technoeconomic analysis based on the pilot‐scale data indicated that the cost of heterotrophic cultivation of microalgae for biomass production is comparable with that of the open‐pond system and much lower than that of tubular PBR, if the biomass yield was higher than 200 g/L. This study demonstrated the economic viability of heterotrophic cultivation on large‐scale microalgal inocula production, but ultrahigh‐productivity fermentation is a prerequisite. Moreover, the advantages of the combined heterotrophic and photoautotrophic cultivation of microalgae for biofuels production were also verified in the pilot‐scale.
Cellular localization of cytochrome bd in cyanobacteria using genetic code expansion
Authors: Cohen Mor , Ozer Eden , Kushmaro Ariel , Alfonta Lital
Published: October 2019

Photosynthesis is one of the most fundamental and complex mechanisms in nature. It is a well‐studied process, however, some photosynthetic mechanisms are yet to be deciphered. One of the many proteins that take part in photosynthesis, cytochrome bd, is a terminal oxidase protein that plays a role both in photosynthesis and in respiration in various organisms, specifically, in cyanobacteria. To clarify the role of cytochrome bd in cyanobacteria, a system for the incorporation of an unnatural amino acid into a genomic membrane protein cytochrome bd was constructed in Synechococcus sp. PCC7942. N‐propargyl‐
l‐lysine (PrK) was incorporated into mutants of cytochrome bd. Incorporation was verified and the functionality of the mutant cytochrome bd was tested, revealing that both electrochemical and biochemical activities were relatively similar to those of the wild‐type protein. The incorporation of PrK was followed by a highly specific labeling and localization of the protein. PrK that was incorporated into the protein enabled a “click” reaction in a bio‐orthogonal manner through its alkyne group in a highly specific manner. Cytochrome bd was found to be localized mostly in thylakoid membranes, as was confirmed by an enzyme‐linked immunosorbent assay, indicating that our developed localization method is reliable and can be further used to label endogenous proteins in cyanobacteria.
Survival of aging CD264+ and CD264− populations of human bone marrow mesenchymal stem cells is independent of colony‐forming efficiency
Authors: Madsen Sean D. , Jones Sean H. , Tucker H. Alan , Giler Margaret K. , Muller Dyllan C. , Discher Carson T. , Russell Katie C. , Dobek Georgina L. , Sammarco Mimi C. , Bunnell Bruce A. , O'Connor Kim C.
Published: October 2019

In vivo mesenchymal stem cell (MSC) survival is relevant to therapeutic applications requiring engraftment and potentially to nonengraftment applications as well. MSCs are a mixture of progenitors at different stages of cellular aging, but the contribution of this heterogeneity to the survival of MSC implants is unknown. Here, we employ a biomarker of cellular aging, the decoy TRAIL receptor CD264, to compare the survival kinetics of two cell populations in human bone marrow MSC (hBM‐MSC) cultures. Sorted CD264+ hBM‐MSCs from two age‐matched donors have elevated β‐galactosidase activity, decreased differentiation potential and form in vitro colonies inefficiently relative to CD264− hBM‐MSCs. Counterintuitive to their aging phenotype, CD264+ hBM‐MSCs exhibited comparable survival to matched CD264− hBM‐MSCs from the same culture during in vitro colony formation and in vivo when implanted ectopically in immunodeficient NIH III mice. In vitro and in vivo survival of these two cell populations were independent of colony‐forming efficiency. These findings have ramifications for the preparation of hBM‐MSC therapies given the prevalence of aging CD264+ cells in hBM‐MSC cultures and the popularity of colony‐forming efficiency as a quality control metric in preclinical and clinical studies with MSCs.
Purification and Kinetic Characterization of the Essential Condensation Enzymes Involved in Prodiginine and Tambjamine Biosynthesis
Authors: Picott Katherine J. , Deichert Julie A. , deKemp Ella M. , Snieckus Victor , Ross Avena C.
Published: October 2019

Prodiginines and tambjamines are related families of bioactive alkaloid natural products with pharmaceutical potential. Both compound families result from a convergent biosynthetic pathway ending in the condensation of a conserved bipyrrole core with a variable partner. This reaction is performed by unique condensation enzymes, and has the potential to be manipulated to produce new pyrrolic compounds. We have purified and reconstituted the in vitro activity of the condensation enzymes PigC and TamQ from Pseudoalteromonas sp., which are involved, respectively, in the prodiginine and tambjamine biosynthetic pathways. Kinetic analysis confirmed a Uni Uni Bi Uni ping‐pong reaction sequence with competitive and uncompetitive substrate inhibition for PigC and TamQ respectively. The kinetic parameters of each enzyme provide insight into their differing substrate scope, and suggest that TamQ may have evolved a wide substrate tolerance that can be used for the production of novel prodiginines and tambjamines.
Review on Photogenerated Hole Modulation Strategies in Photoelectrocatalysis for Solar Fuel Production
Authors: Sun Rui , Zhang Ziqing , Li Zhijun , Jing Liqiang
Published: October 2019

Photoelectrocatalytic (PEC) technique provides a clean, low‐cost, and environmental‐friendly route with great potential for addressing energy crisis mainly through water splitting and CO2 reduction by utilizing solar energy. In general, it is favorable for the added external electric field to greatly modulate the photogenerated electrons in PEC process. However, it is a rate‐determining step as another half‐reaction for the photogenerated hole to induce water oxidation since it is usually involved with 4 electrons for O2 evolution. Thus, it is highly desired to develop feasible strategies to modulate photogenerated hole for efficient solar‐to‐energy conversion. Unfortunately, it is frequently neglected compared to the electron regulation. Obviously, it is much meaningful to develop new efficient strategies for photogenerated hole modulation, along with to review recent developments. Herein, this minireview summarizes the recent developments of photoexcited hole modulation for PEC process to nanosized semiconductors, and it is highlighted for the strategies successfully developed in our group in recent years, mainly including surface polarization by modifying inorganic acids and halogen anions, and non‐metallic element doping. Moreover, related conclusions and several outlooks are put forward.
Synthesis of Ni−MoSx/g‐C3N4 for Photocatalytic Hydrogen Evolution under Visible Light
Authors: Wang Bo , Li Xia , Wu Haining , Xu Guangqing , Zhang Xinyi , Shu Xia , Lv Jun , Wu Yucheng
Published: October 2019

Graphitic carbon nitride loaded with MoSx nanodots (MoSx/g‐C3N4) was synthesized through a sonochemical method. MoSx nanodots (3∼20 nm) are shown to have the same excellent co‐catalytic H2 evolution performance as that of Pt. Nevertheless, the photocatalytic activity of MoSx/g‐C3N4 decreased with time. To overcome this instability, we show that co‐incorporation of Ni can significantly reduce the photo‐corrosion. The rate of H2 evolution of Ni−MoSx/g‐C3N4 photocatalyst reaches a maximum of 5968 μmol h−1 g−1, which is 89 % higher than that of Pt/g‐C3N4. The element mapping images show that Ni is deposited on the surface of MoSx. The co‐presence of Ni and MoSx not only enhance optical light absorption by g‐C3N4, but also significantly improve the separation efficiency of photocarriers and thus the photocatalytic hydrogen evolution efficiency.
The Capacitive Behavior of Polyluminol on Carbon Nanotubes Electrodes
Authors: N'Diaye Jeanne , Hyun Chang Jin , Lian Keryn
Published: October 2019

A polymerized luminol carbon nanotube (CNT) composite electrode was developed via an in situ chemical polymerization (CpLum) process. Density functional theory (DFT) simulation suggested the luminol molecules were preferentially aligned flat on the CNTs. This was further demonstrated through a morphological study, which showed the CpLum wrapped around each CNT homogeneously with an average thickness of 4.5±1.5 nm. The surface chemical analysis by X‐ray photoelectron spectroscopy (XPS) revealed a progressive increase in the nitrogen content and stabilized at 9 %. Deconvolution of the high‐resolution N 1s spectra suggested the presence of secondary and tertiary amine functional groups, which are the signatures of polymerized luminol. The composite electrodes exhibited a pseudocapacitive‐like behavior with 3.5 times increase in charge storage. The contributions from the CpLum coating and CNT substrate were differentiated and were further deconvoluted to quantify the capacitive charge storage of each component. The thin CpLum coating contributed 70 % of the total charge storage through pseudocapacitance. CpLum‐CNT electrodes also showed a high rate capability and good cycling stability, very promising for electrochemical capacitors.
Hole Migration in Telomere‐Based Oligonucleotide Anions and G‐Quadruplexes
Authors: Li Wen , Mjekiqi Edita , Douma Wessel , Wang Xin , Kavatsyuk Oksana , Hoekstra Ronnie , Poully Jean‐Christophe , Schlathölter Thomas
Published: October 2019

Vacuum ultraviolet photoionization of a gas‐phase oligonucleotide anion leads to the formation of a valence hole. This hole migrates towards an energetically favorable site where it can weaken bonds and ultimately lead to bond cleavage. We have studied Vacuum UV photoionization of deprotonated oligonucleotides containing the human telomere sequence dTTAGGG and G‐quadruplex structures consisting of four dTGGGGT single strands, stabilized by NH4+ counter ions. The oligonucleotide and G‐quadruplex anions were confined in a radiofrequency ion trap, interfaced with a synchrotron beamline and the photofragmentation was studied using time‐of‐flight mass spectrometry. Oligonucleotide 12‐mers containing the 5'‐TTAGGG sequence were found to predominantly break in the GGG region, whereas no selective bond cleavage region was observed for the reversed 5'‐GGGATT sequence. For G‐quadruplex structures, fragmentation was quenched and mostly non‐dissociative single and double electron removal was observed.
Annulation of Oxime‐Ether Tethered Donor–Acceptor Cyclopropanes
Authors: Irwin Lauren C. , Allen Meredith A. , Vriesen Matthew R. , Kerr Michael A.
Published: October 2019

Novel oxime‐ether tethered cyclopropanes, when exposed to Yb(OTf)3 and heat, annulate to generate hydropyrrolo‐oxazines products that can be taken to their respective pyrrolidines via hydrogenative N−O bond cleavage. The hydropyrrolo‐oxazines are generated in a diastereoselective manner isolating the cis or trans product based on the temperature of the reaction. 20 examples of selective cis and trans hydropyrrolo‐oxazines were generated in high yields by temperature control.
Are parental changes related to improvements in preschool children's disruptive behaviours?
Authors: van der Veen‐Mulders Lianne , Hoekstra Pieter J. , Nauta Maaike H. , van den Hoofdakker Barbara J.
Published: October 2019

Objective

To investigate whether changes in parenting after behavioural parent training in routine clinical care are associated with improvements in preschool children's disruptive behaviours.

Method

We evaluated changes after parent training in maternal and paternal self‐reports of parental discipline practices parenting sense of competence, and parents' ratings of child disruptive behaviours in parents of 63 children, with a one group pretest–posttest design. We also compared parenting parameters in this clinical sample with a nonclinical sample (n = 121).

Results

Mothers' self‐reports of parental discipline practices and parenting sense of competence significantly improved after behavioural parent training. Less over‐reactivity in both mothers and fathers was associated with fewer disruptive behaviours in children. After parent training, mothers' ratings of their discipline techniques did not differ anymore from those in the nonclinical sample.

Conclusion

Positive changes in parental discipline practices, particularly less over‐reactive parental behaviours, were related to a decrease of disruptive child behaviours.
11C‐Labeling: Intracyclic Incorporation of Carbon‐11 into Heterocycles
Authors: Liger François , Cadarossanesaib Florence , Iecker Thibaut , Tourvieille Christian , Le Bars Didier , Billard Thierry
Published: October 2019

Labeling of heterocycles with carbon‐11 is generally performed through peripheral functionalizations and more scarcely inside heterocyclic core. Such less common approach usually requires preliminary multi‐step synthesis of reactive species. Herein, a cyclization reaction by direct use of cyclotron‐produced [11C]CO2 is described to obtain various heterocycles intracyclically labeled in only 10 minutes.
Proteomics comparison of exosomes from serum and plasma between ultracentrifugation and polymer‐based precipitation kit methods
Authors: Cao Feng , Gao Ying , Chu Qiao , Wu Qi , Zhao Lin , Lan Tao , Zhao Liang
Published: October 2019

Exosomes are vesicles with sizes ranging from 30 to 150 nm. The analysis and detection of blood exosomes offers an effective route for cancer diagnosis, prognosis assessment, and therapeutic evaluation of diseases. Due to the difference in separation procedure, collection method and the usage of anticoagulants, serum and plasma samples show diversity test results. In order to evaluate the isolation effect of exosomes in serum and plasma samples, two commonly used exosomal isolation methods, ultracentrifugation and polymer‐based precipitation kit, were used, respectively. And the isolation effects were evaluated by comparing the composition and abundant of proteins from isolated exosomes based on MS‐based proteomics analysis. The results showed that the plasma exosomes extracted by ultracentrifugation identified more exosome biomarkers, and the concentrations of these biomarkers were higher than others. And plasma exosomes could be a better sample for blood‐based proteomics research of exosomes. It would be more useful for future targeted biomarker discovery.
Analysis of impeller blade parameters and tip clearance of turboexpander in organic Rankine cycle system
Authors: Jia Wenguang , Wang Chuanwei , Zhang Kerui , Feng Shaohua , Yan Jinglu , Liu Bingcheng
Published: October 2019

The optimization of a turboexpander can significantly improve the performance of the organic Rankine cycle (ORC) system, which can use in low‐temperature geothermal energy for high‐efficiency power generation. Therefore, this paper studies and optimizes the expander in the ORC of low‐temperature geothermal energy around 90°C. Firstly, the influence of impeller parameters on the performance of the expander is analyzed. Then, the grid is divided by the turbine mesh, and numerical simulation is performed by CFX. The gas state equation selects the Peng–Robinson equation, and the turbulence equation selects the SST model. Finally, the effect of tip clearance on the performance of the expander was studied. Research on impeller blade parameters shows that with the increase in the outer diameter of the impeller blade outlet, the isentropic efficiency of the expander decreases, and the output power increases. As the increase in the angle between the direction of the impeller blade and the meridian plane, the outlet velocity of the blade increases, the temperature decreases, and the efficiency and control of the turboexpander will decrease. The meridional section width has few effects on the performance of the expander. The study of the tip clearance by numerical simulation shows that the existence of tip clearance will cause clearance flow between pressure surface and suction surface that interferes with the mainstream direction. When the tip clearance increases from 0 mm to 1.2 mm, the efficiency of the expander is reduced by 8.9%.
Favorable prognosis in pediatric brainstem low‐grade glioma: Report from the German SIOP‐LGG 2004 cohort
Authors: Holzapfel Johannes , Kandels Daniela , Schmidt René , Pietsch Torsten , Warmuth‐Metz Monika , Bison Brigitte , Krauss Jüergen , Kortmann Rolf‐Dieter , Timmermann Beate , Thomale Ulrich‐Wilhelm , Albert Michael H. , Hernáiz Driever Pablo , Witt Olaf , Gnekow Astrid K.
Published: October 2019

Reports on pediatric low‐grade glioma (LGG) of the caudal brainstem are retrospective with heterogeneous cohorts, variable treatments and inconsistent outcome data. We analyzed their natural history and asked whether brainstem location proved unfavorable for survival within the framework of the comprehensive SIOP‐LGG 2004 management strategy. Within the prospectively registered, population‐based German SIOP‐LGG 2004 cohort 116 patients (age 0.2–16.5 years, 10% Neurofibromatosis NF1) were diagnosed with LGG of the pons (27%) and medulla oblongata (73%). After biopsy (23%), variable resection (63%) or radiologic diagnosis only (14%), 59 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemo‐ (n = 39) or radiotherapy (n = 18). After further progression (28/57), salvage treatments included multiple treatment lines for 12/28 patients. Five‐years event‐free survival dropped to 0.40, while 5‐years overall survival was 0.95 (median observation time 6.8 years). Higher extent of resection yielded lower progression rate (p = 0.001), but at a cost of 21/100 patients suffering from new postsurgical complications including respiratory insufficiency. Central review confirmed pilocytic astrocytoma (56%), diffuse astrocytoma (8%) or glioneuronal histology (16%) (others 4%, no histology 17%). Malignant evolution was documented in five patients associated with Histone3 mutation in 2/5. Our treatment algorithm conveyed high overall survival for pediatric brainstem LGG. Extensive neurosurgical resection did increase additional postoperative neurologic deficits but not overall survival in this often‐chronic disease. More than half of all patients can be safely followed by observation, while multimodal adjuvant treatment can control progressive tumors. Molecular assessment should confirm low‐grade diagnosis and may detect patterns prognostic for malignant evolution.
miR‐146a interacting with lncRNA EPB41L4A‐AS1 and lncRNA SNHG7 inhibits proliferation of bone marrow‐derived mesenchymal stem cells
Authors: Cui Penglei , Zhao Xiaoying , Liu Jinlong , Chen Xiaodong , Gao Yuan , Tao Kun , Wang Chuandong , Zhang Xiaoling
Published: October 2019

Emerging evidence suggests that microRNA plays a pivotal role in cell proliferation. Our previous research has certified that miR‐146a attenuates osteoarthritis through the regulation of cartilage homeostasis. However, little information about the function of miR‐146a in bone marrow‐derived mesenchymal stem cells (BMSCs) proliferation and the underlying mechanism was available. Therefore, this study aims at investigating the role of miR‐146a on the proliferation of BMSCs and the possible mechanisms involved. The function of miR‐146a on BMSCs proliferation was studied through overexpression and knockdown of miR‐146a or the indicated long noncoding RNAs (lncRNAs) in BMSCs and then the proliferation rate of the BMSCs were detected by Cell Counting Kit‐8 assay, colony formation assay. Besides, flow cytometry was used to test the cell cycle state of BMSCs modified by overexpression or knockdown of miR‐146a or lncRNA EPB41L4A‐AS1 (EPB41L4A Antisense RNA 1) and small nucleolar RNA host gene 7 (SNHG7). The expression level of marker genes involved in modulating cell proliferation was evaluated by quantitative polymerase chain reaction and western blot analysis. We discovered that the knockdown of miR‐146a significantly promoted BMSCs proliferation. Moreover, miR‐146a could bind to and inhibit endogenous expression of EPB41L4A‐AS1 and SNHG7. Further study demonstrated that overexpression of EPB41L4A‐AS1 and SNHG7 significantly enhanced proliferation of BMSCs. For the first time, we certified that miR‐146a suppressed BMSCs proliferation, but EPB41L4A‐AS1 and SNHG7 promoted BMSCs proliferation in the present study. Mechanistically, miR‐146a significantly inhibited BMSCs proliferation partly through miR‐146a/EPB41L4A‐AS1 SNHG7/cell proliferation signaling pathway axis.
NDRG2andTLR7as novel DNA methylation prognostic signatures for acute myelocytic leukemia
Authors: Ge Fei , Zhang Ping , Niu Junwei , Pei Xiaohang , Lian Cheng , Yu Runhong , Ma Rongjun , Zhang Yin , Zhu Zunmin , Sun Kai
Published: October 2019

Acute myelocytic leukemia (AML) is an aggressive malignant tumor and typically fatal without treatment. Identification and development of novel biomarkers could be beneficial for the diagnosis and prognosis of AML patients. Here, we aimed to identify the accurate DNA methylation prognostic signatures for AML patients. The DNA methylation data of AML patients and corresponding clinical information were retrieved from The Cancer Genome Atlas database. CPG sites that correlates closely with the survival of the AML patients were identified and further combined into CPG sites pairs to screen the survival‐related pairs. The prognostic signatures were identified by the C‐index and forward search algorithms and validated by the verification group. Finally, the functional enrichment analysis was performed on these CPG sites. As a result, a total of 498 CPG sites associated with the overall survival of AML patients was obtained. A prognostic signature composed of 10 CPG sites pairs was obtained and validated. The functional enrichment analysis showed prognostic genes were mainly enriched in tumor protein processing, cell differentiation, blood leukocyte immunity, and platelet growth factor pathways. In summary, we identified two accurate prognostic methylation signatures (NDRG2andTLR7), which would be served as a novel therapy target for AML.
Role of Sonic hedgehog signaling in cell cycle, oxidative stress, and autophagy of temozolomide resistant glioblastoma
Authors: Honorato Jessica R. , Hauser‐Davis Rachel A. , Saggioro Enrico M. , Correia Fábio V. , Sales‐Junior Sidney F. , Soares Lorena O. S. , Lima Leandro da R. , Moura‐Neto Vivaldo , Lopes Giselle P. de F. , Spohr Tania C. L. de S.
Published: October 2019

The first‐line chemotherapy treatment for Glioblastoma (GBM) ‐ the most aggressive and frequent brain tumor ‐ is temozolomide (TMZ). The Sonic hedgehog (SHH) pathway is involved with GBM tumorigenesis and TMZ chemoresistance. The role of SHH pathway inhibition in the potentiation of TMZ's effects using T98G, U251, and GBM11 cell lines is investigated herein. The combination of GANT‐61 and TMZ over 72 hr suggested a synergistic effect. All TMZ‐resistant cell lines displayed a significant decrease in cell viability, increased DNA fragmentation and loss of membrane integrity. For T98G cells, G2/M arrest was observed, while U251 cells presented a significant increase in reactive oxygen species production and catalase activity. All the cell lines presented acidic vesicles formation correlated to Beclin‐1 overexpression. The combined treatment also enhanced GLI1 expression, indicating the presence of select resistant cells. The selective inhibition of the SHH pathway potentiated the cytotoxic effect of TMZ, thus becoming a promising in vitro strategy for GBM treatment.
A novel risk signature that combines 10 long noncoding RNAs to predict neuroblastoma prognosis
Authors: Gao Li , Lin Peng , Chen Peng , Gao Rui‐Zhi , Yang Hong , He Yun , Chen Jia‐Bo , Luo Yi‐Ge , Xu Qiong‐Qian , Liang Song‐Wu , Gu Jin‐Han , Huang Zhi‐Guang , Dang Yi‐Wu , Chen Gang
Published: October 2019

Neuroblastoma (NBL) is the most frequently encountered extracranial solid neoplasm and impacts significantly on the survival of patients, especially in cases of advanced tumor stage or relapse. A long noncoding RNA (lncRNA) signature to predict the survival of patients with NBL is proposed in this paper. Differentially expressed lncRNA (DElncRNA) was selected using the Limma plus Voom package inRbased on the RNA‐sequencing data downloaded from the Therapeutically Applicable Research To Generate Effective Treatments database and Genotype‐Tissue Expression database. Univariate cox regression analysis, least absolute shrinkage and selection operator regression analysis, and multivariate cox regression analysis were conducted to identify candidate DElncRNAs for the risk signature. Consequently, 10 DElncRNAs were designated as candidate DElncRNAs for the risk signature. Time‐dependent receiver operating characteristic curves and Kapan–Meier survival curves confirmed the efficacy of the risk signature in predicting the survival of patients with NBL (area under the curve = 0.941;p ≤ .001). One of the DElncRNA constituent subparts (LINC01010) was significantly associated with the survival outcome of patients with NBL in GSE62564 (p = .004). Thus, a risk signature comprising 10 DElncRNAs was identified as effective for individual risk stratification and the survival prediction outcomes of patients with NBL.
Comparison of human‐induced pluripotent stem cells and mesenchymal stem cell differentiation potential to insulin producing cells in 2D and 3D culture systems in vitro
Authors: Abazari Mohammad Foad , Nasiri Navid , Nejati Fatemeh , Zare Karizi Shohreh , Amini Faskhodi Mojdeh , Saburi Ehsan , Aghapur Nasrin , Mahdavi Mohammad Reza , Ardeshirylajimi Abdolreza , Enderami Seyed Ehsan , Soleimanifar Fatemeh
Published: October 2019

Diabetes is one of the most common diseases in the world that is chronic, progressive, and costly, and causes many complications. Common drug therapies are not able to cure it, and pancreas transplantation is not responsive to the high number of patients. The production of the insulin producing cells (IPCs) from the stem cells in the laboratory and their transplantation to the patient's body is one of the most promising new approaches. In this study, the differentiation potential of the induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) into IPCs was compared to each other while cultured on poly(lactic‐co‐glycolic) acid (PLGA)/polyethylene glycol (PEG) nanofibrous scaffold as a 3D substrate and tissue culture polystyrene (TCPS) as a 2D substrate. Although the expression level of the insulin, Glut2 and pdx‐1 genes in stem cells cultured on 3D substrate was significantly higher than the stem cells cultured on 2D substrate, the highest expression level of these genes was detected in the iPSCs cultured on PLGA‐PEG. Insulin and C‐peptide secretions from differentiated cells were also investigated and the results showed that secretions in cultured iPSCs on the PLGA‐PEG were significantly higher than cultured iPSCs on the TCPS and cultured MSCs on both PLGA‐PEG and TCPS. In addition, insulin protein was also expressed in the cultured iPSCs on the PLGA‐PEG significantly higher than cultured MSCs on the PLGA‐PEG. It can be concluded that differentiation potential of iPSCs into IPCs is significantly higher than human MSCs at both 2D and 3D culture systems.
MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction
Authors: Huang Dezhi , Jiang Yugang
Published: October 2019

MAP kinase phosphatase 1 (MKP1) has been identified as an antiapoptotic protein via sustaining mitochondrial function. However, the role of MKP1 in neuroinflammation has not been fully understood. The aim of this study is to figure out the influence of MKP1 in lipopolysaccharide (LPS)‐treated microglia BV‐2 cells and investigate whether MKP1 reduces BV‐2 cell death via modulating endoplasmic reticulum (ER) stress and mitochondrial dysfunction. The results of this study demonstrated that MKP1 was rapidly downregulated after exposure to LPS. However, the transfection of MKP1 adenovirus could reverse cell viability and attenuate LPS‐mediated BV‐2 cell apoptosis. Mechanistically, MKP1 overexpression alleviated ER stress and corrected LPS‐induced calcium overloading. Besides, MKP1 adenovirus transfection also reversed mitochondrial bioenergetics, maintained mitochondrial membrane potential, and blocked mitochondria‐initiated apoptosis signals. Furthermore, we found that MKP1 overexpression is associated with inactivation of mitogen‐activated protein kinase–c‐Jun N‐terminal kinase (MAPK–JNK) pathway. Interestingly, the activation of MAPK–JNK pathway could abolish the protective effects of MKP1 on BV‐2 cells survival and mitochondrial function in the presence of LPS. Altogether, our results identified MKP1 as a primary defender of neuroinflammation via modulating ER stress and mitochondrial function in a manner dependent on MAPK–JNK pathway. These findings may open a new window for the treatment of neuroinflammation in the clinical setting.
Practicing mind‐body medicine before Freud: John G. Gehring, the “Wizard of the Androscoggin”
Authors: Harris Ben , Stevens Courtney J.
Published: October 2019

This article describes the psychotherapy practice of physician John G. Gehring and places it in historical context. Forgotten today, Gehring was a highly sought‐after therapist from the 1890s to the 1920s by prominent figures in the arts, sciences, business, and law. He practiced a combination of work therapy, suggestion, and autosuggestion that has similarities to Cognitive Behavior Therapy and Behavioral Activation. Using biographies, memoirs, and archival records, the details of Gehring's work are reconstructed and the reasons for its success are analyzed. His invisibility in the history of psychiatry is attributed to the later dominance of Freudianism within the field.
Neurochemical abnormalities in patients with type 1 Gaucher disease on standard of care therapy
Authors: Kartha Reena V. , Joers James , Terluk Marcia R. , Travis Abigail , Rudser Kyle , Tuite Paul J. , Weinreb Neal J. , Jarnes Jeanine R. , Cloyd James C. , Öz Gülin
Published: October 2019

Type 1 Gaucher disease (GD1), a glycosphingolipid storage disorder caused by deficient activity of lysosomal glucocerebrosidase, is classically considered non‐neuronopathic. However, current evidence challenges this view. Multiple studies show that mutations in GBA1 gene and decreased glucocerebrosidase activity are associated with increased risk for Parkinson disease. We tested the hypothesis that subjects with GD1 will show neurochemical abnormalities consistent with cerebral involvement. We performed Magnetic Resonance Spectroscopy at 7 T to quantify neurochemical profiles in participants with GD1 (n = 12) who are on stable therapy. Age and gender matched healthy participants served as controls (n = 13). Neurochemical profiles were obtained from parietal white matter (PWM), posterior cingulate cortex (PCC), and putamen. Further, in the GD1 group, the neurochemical profiles were compared between individuals with and without a single L444P allele. We observed significantly lower levels of key neuronal markers, N‐acetylaspartate, γ‐aminobutyric acid, glutamate and glutamate‐to‐glutamine ratio in PCC of participants with GD1 compared to healthy controls (P < .015). Glutamate concentration was also lower in the putamen in GD1 (P = .01). Glucose + taurine concentration was significantly higher in PWM (P = .04). Interestingly, individuals without L444P had significantly lower aspartate and N‐acetylaspartylglutamate in PCC (both P < .001), although this group was 7 years younger than those with an L444P allele. This study demonstrates neurochemical abnormalities in individuals with GD1, for which clinical and prognostic significance remains to be determined. Further studies in a larger cohort are required to confirm an association of neurochemical levels with mutation status and glucocerebrosidase structure and function.

Synopsis

Ultrahigh field magnetic resonance spectroscopy reveals abnormalities in neurochemical profiles in patients with GD1 compared to matched healthy controls.
A hybrid shuffled frog‐leaping and pattern search algorithm for load frequency controller design of a two‐area system composing of PV grid and thermal generator
Authors: Khadanga Rajendra Kumar , Kumar Amit , Panda Sidhartha
Published: October 2019

The shuffled frog‐leaping algorithm (SFLA) is a nature‐inspired metaheuristic swarm‐based optimization algorithm, which mimics the social behavior of memetics. The SFLA comprises an arrangement of communicating virtual population of frogs divided into various memeplexes. Many attempts have been made to find the variant of the SFLA that performs better on a variety of optimization tasks by making the original SFLA more complex. This paper proposes the hybrid approach by combining the SFLA algorithm with a pattern search algorithm, which improves the original technique named as the hybrid shuffled frog‐leaping and pattern search algorithm (hSFLA‐PS). The superiority of the proposed hybrid algorithm over the original SFLA in terms of implementation time and solution quality is compared by taking several benchmark test functions. In the next step, the real application of the proposed hybrid approach in the engineering field is done by designing a proportional‐integral‐derivative (PID) controller for frequency regulation of a two‐area power system that is composed of a photovoltaic (PV) grid and a thermal generator. It is observed that the hSFLA‐PS–based PID controller is more effective for the load frequency control compared with conventional controllers tuned with genetic algorithm (GA) and firefly algorithm (FA).
Understanding interaction effect of arbuscular mycorrhizal fungi in rice under elevated carbon dioxide conditions
Authors: Panneerselvam Periyasamy , Sahoo Sowarnalisha , Senapati Ansuman , Kumar Upendra , Mitra Debasis , Parameswaran Chidambaranathan , Anandan Annamalai , Kumar Anjani , Jahan Afrin , Nayak Amaresh Kumar
Published: October 2019

Arbuscular mycorrhizal fungi (AMF), particularly the Glomerales group, play a paramount role in plant nutrient uptake, and abiotic and biotic stress management in rice, but recent evidence revealed that elevated CO2 concentration considerably reduces the Glomerales group in soil. In view of this, the present study was initiated to understand the interaction effect of native Glomerales species application in rice plants (cv. Naveen) under elevated CO2 concentrations (400 ± 10, 550 ± 20, and 700 ± 20 ppm) in open‐top chambers. Three different modes of application of the AMF inoculum were evaluated, of which, combined application of AMF at the seedling production and transplanting stages showed increased AMF colonization, which significantly improved grain yield by 25.08% and also increased uptake of phosphorus by 18.2% and nitrogen by 49.5%, as observed at 700‐ppm CO2 concentration. Organic acids secretion in rice root increased in AMF‐inoculated plants exposed to 700‐ppm CO2 concentration. To understand the overall effect of CO2 elevation on AMF interaction with the rice plant, principal component and partial least square regression analysis were performed, which found both positive and negative responses under elevated CO2 concentration.
Prognostic significance of mucinous component in hilar cholangiocarcinoma after curative‐intent resection
Authors: Lu Jiong , Li Bei , Li Fu‐Yu , Ye Hui , Xiong Xian‐Ze , Cheng Nan‐Sheng
Published: October 2019

Background

The presence of mucinous component has been indicated to have a prognostic value in adenocarcinoma. However, little is known regarding the clinicopathological characteristics and prognosis of hilar cholangiocarcinoma (HC) with mucinous component (HCM).

Methods

Between January 1996 and December 2014, a total of 61 HCM patients who underwent curative‐intent resection at West China Hospital were retrospectively reviewed. The clinicopathological characteristics and survival of these patients were compared with a large cohort of 217 surgically resected conventional HC patients during the same period.

Results

The clinicopathological characteristics of HCM were distinct from conventional HC, including higher CA19‐9 levels, larger tumor sizes, less differentiation, and a high frequency of liver parenchyma invasion, portal vein invasion, and lymphovascular invasion. HCM patients showed significantly worse recurrence‐free survival (13.4 vs 23.9 months; P = .011) and overall survival (18.2 vs 32.1 months; P = .019) compared with conventional HC patients. Multivariate analysis confirmed liver parenchyma invasion, N stage, surgical margin, and histological grade as independent prognostic factors influencing overall survival in HCM patients.

Conclusion

HCM showed distinct clinicopathological features, more aggressive biological behaviors, and poor prognosis in comparison with conventional HC. Therefore, the mucinous component is an adverse prognostic factor for HC.
Potential survival benefit of radiofrequency ablation for small solitary intrahepatic cholangiocarcinoma in nonsurgically managed patients: A population‐based analysis
Authors: Wu Lu , Tsilimigras Diamantis I. , Farooq Ayesha , Hyer J. Madison , Merath Katiuscha , Paredes Anghela Z. , Mehta Rittal , Sahara Kota , Shen Feng , Pawlik Timothy M.
Published: October 2019

Background

Little data regarding the selection of nonsurgical therapies for localized intrahepatic cholangiocarcinoma (ICC) are available.

Methods

A cohort of nonsurgically managed patients with American Joint Commission on Cancer clinical stage I/II ICC in the United States from 2004 to 2013 were identified in the National Cancer Database. Overall survival (OS) was compared according to treatment options (radiofrequency ablation [RFA] vs chemoradiotherapy) using propensity‐score matching.

Results

Among 505 patients, 86 patients were treated with RFA and 419 patients were treated with chemoradiotherapy. After propensity matching (n = 84, each group), 5‐year OS was 17.6% among patients who underwent RFA vs 3.8% among patients receiving chemoradiotherapy (P < .001). On bivariate analysis, RFA was related to an OS benefit (hazard ratio, 0.46; 95% confidence interval, 0.33‐0.66; P < .001). Specifially, a stage‐specific subgroup analysis revealed a survival benefit in favor of RFA among stage I patients (5‐year OS; RFA: 20.1% vs chemoradiotherapy: 3.7%, P < .001), whereas no difference in OS was noted among patients with stage II disease.

Conclusion

Among ICC patients with small (≤5 cm), solitary ICC without vascular invasion, RFA was associated with better survival compared with chemoradiotherapy.
Engineered oncolytic virus for the treatment of cholesteatoma: A pilot in vivo study
Authors: Samy Ravi N. , Earl Brian R. , Lipschitz Noga , Schweinzger Ivy , Currier Mark , Cripe Timothy
Published: October 2019

Objective

Determine if oncolytic herpes simplex virus (oHSV) can eradicate cholesteatoma (CHST) in a gerbil model.

Methods

An in vivo model of CHST was developed in Mongolian gerbils by combining Pseudomonas aeruginosa inoculation with double ligation of the external auditory canal (EAC). CHST size and bone thickness were measured using morphometric and volumetric quantification techniques via micro‐computed tomography (micro‐CT). The CHST induction and quantification techniques were then used in an additional group of 10 gerbils (n = 20 ears) to determine the within‐group treatment efficacy of oHSV against CHST in vivo. Treated animals received either one, two, or three intrabullar injections of oHSV between 2 and 6 weeks postinduction of CHST.

Results

The P. aeruginosa inoculation plus double EAC ligation technique successfully induced a range of CHST growth in 100% of the ears in the model‐development group. Osteolytic effects of CHST were observed in 6% of ears whereas osteoblastic effects were observed in 31% of ears. CHST volume decreased by 50% or more in 12 of the 20 ears in the oHSV‐treatment groups. An apparent reversal of osteoblastic effects was also observed in three out of four ears 6 weeks following the third oHSV injection.

Conclusions

P. aeruginosa inoculation plus double EAC ligation reliably induces CHST formation in gerbil. CT‐based volumetric measures are significantly more accurate than single‐slice morphometric area measures for quantification of CHST size. Treatment with oHSV appears to be efficacious for reducing CHST volume by as much as 77% with as few as one treatment.

Level of Evidence

NA
Large Area Thick Films of PVDF‐TrFE and Relaxor‐Ceramics for Piezo‐ and Pyroelectric Applications
Authors: Dietze Matthias , Es‐Souni Mohammed
Published: October 2019

Wearable electronics, sensors, and energy harvesting devices are gaining an ever increasing importance in consumer products. Their success is, however, contingent on the availability of flexible and cost‐effective functional materials. The present paper presents an up‐scaled processing route for 0–3 thick film composites of the ferroelectric polymer polyvinylidenefluoride‐trifluoroethylene and a relaxor ceramic. Different compositions are investigated for pyro‐ and piezoelectric applications. Various samples are produced via tape casting and spin‐coating as freestanding and supported films of up to 600 × 200 mm² and on 150 mm silicon wafers, respectively. The samples are characterized in terms of thickness and roughness reproducibility, mechanical properties, and impedance. It is shown that good reproducibility and quality of the films can be realized. Depending on the application targeted (pyroelectric or piezoelectric), specific compositions together with the suitable poling process are presented. For instance, a composite with 24 vol% ceramic shows highest pyroelectric properties together with lowest piezoelectric thickness coefficient (d33) when poled for pyroelectric applications. On the other hand, a composite with 50 vol% ceramic exhibits a d33 of 100 pm V−1 that is unsurpassed for this type of composites. These properties are advantageous in a large variety of applications, including wearable devices.
The role of N6‐methyladenosine modification on diapause in silkworm (Bombyx mori) strains that exhibit different voltinism
Authors: Jiang Tao , Li Jiashuang , Qian Ping , Xue Peng , Xu Jin , Chen Yanrong , Zhu Juan , Tang Shunming , Zhao Qiaoling , Qian Heying , Shen Xingjia
Published: October 2019

N6‐methyladenosine (m6A) plays a key role in regulating gene expression in myriad organisms. Diapause is an important plastic phenotype that allows insects to survive under specific environmental conditions. However, the diapause molecular mechanism remains unknown. In this study, we analyzed the phylogenetics of genes related to the m6A modification complex in the silkworm (Bombyx mori) based on identified sequences from other organisms. We detected the expression of these genes during different developmental phases from four strains with different voltinism. We also determined total m6A content in cells treated with different diapause hormone concentrations or eggs exposed to hydrochloric acid. Our data revealed that m6A‐modification‐related gene expression and m6A content were greater in diapause‐destinated compared to nondiapause‐destined strains. Our findings suggest that m6A modification may provide significant epigenetic regulation of diapause‐related genes in the silkworm.