bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality Effectiveness Analysis Assessment of Physics Teaching Materials-oriented ICARE Method on Student Cognitive Mastery Based Experiment Skill Level
Authors: Sinuraya Jurubahasa , Panggabean Deo Demonta , Wahyuni Ida
Published: October 2019

Aims: The aim of the study was for quality effectiveness analysis assessment of physics teaching materials-oriented ICARE methods on student cognitive mastery-based experiment skill levels.

Study Design: Teaching materials accompanied by ICARE-oriented worksheets are printed learning materials that are packaged in the form of books in which each subject matter is arranged sequentially: discussion of important concepts, sample questions, cognitive questions, and worksheets arranged systematically in the order of introduction, connecting, applying, reflecting, extending (ICARE) to hone students' science process skills. The method is done by dividing students based on experiment skill level from the results achieved by the cognitive mastery test. Each group is given 3 subjects to work on based on the ICARE Stage and is guided by physics teaching materials-oriented ICARE method.

Place of Study: Sample: Department of Physics Education, Universitas Negeri Medan, Medan, Indonesia.

Methodology: Science Process Skills Students are divided into 3 main indicators in the experiment namely Problem / Case Identification (Observation, Problem Formulation, & Create Hypothesis); Experiment (Verifications, Variable Manipulation, Data Collection); & Evaluation (Interpretation, Data Analysis & Theory, Create A Scene). The three main indicators in Experiment are adjusted to the ICARE Stages.

Results: From the results of the study, the use of physics teaching materials-oriented ICARE methods used at Universitas Negeri Medan was more effective with the Intermediate level group. Conformity is due to habit factors that are carried out during learning. It is very important to improve and develop the physics teaching materials-oriented ICARE method in its use in learning. It is necessary to add strict instructions as facilitators at the ICARE stage and some improvements to the structure of submitting assignments that are directive and important to keep on doing.

Conclusion: This is very necessary to direct the activities of students and the creativity of thinking of students without ignoring some of the stages possessed by physics teaching materials-oriented ICARE method.
Drug Excipient Compatibility Testing Protocols and Charaterization: A Review
Authors: Gupta Krishna R. , Pounikar Anita R. , Umekar Milind J.
Published: October 2019

Drug molecule contains various reactive functional groups which are susceptible to react with another reactive functional groups which might be excipients, excipient or drugs impurities formed during manufacturing or storage. The objective of the current review article is to provide a comprehensive review of excipients-drug compatibility study, their degradation product characterization with different analytical methods and further impact of methodologies in pharmaceutical industry for potential stability assessment. The incompatibility of drug excipient was very common due to the reactive functional groups in drugs and excipients. These leads to formation of drug related impurities as well as excipient impurities reaction with active Pharmaceutical Ingredients. Sometimes these impurities found to be mutagenic and genotaxic to human beings. Identification of drug degradation in presence of excipient impurities requires extensive knowledge and adequate analytical characterization data. Systematic literature review and understanding about the drug-excipient chemistry in formulation process is important criteria to select compatible excipient and formulate ideal formulation. The analytical characterization data gives idea about degradation pathway. This paper discusses drug-excipient interactions, compatibility and characterization by different analytical methods with case studies and provides an overview of different excipients compatibility in formulation.
Iron‐Promoted Reductive Ring‐Opening and Isomerization Reactions of C4‐Alkynylisoxazoles Leading to 2‐Alkynylenaminones and Polysubstituted Furans
Authors: Yang Wen , Chen Yu , Yao Yongqi , Lin Qifu , Yang Dingqiao
Published: October 2019

A new iron(III)‐promoted reductive ring‐opening and isomerization reactions of C4‐alkynylisoxazoles in the oxidized N‐methylpyrrolidone (NMP*) was reported. By changing the substituents at the C3 and C5 position of the isoxazole ring, the reaction selectively produced 2‐alkynylenaminones and polysubstituted furans in good to excellent yields. It was very interesting that large group at the C3 or C5 position of the isoxazole ring was a steric hindrance tertiary butyl group (t‐Bu), the reaction proceeded ring‐opening rather than isomerization reaction in the presence of FeCl3. It was noteworthy that the NMP* as a solvent and a hydrogen donor was essential for both reactions. A plausible mechanism for the reductive ring‐opening and isomerization was also proposed.

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Imparting Multifunctionality by Utilizing Biporosity in a Zirconium‐Based Metal–Organic Framework
Authors: Jadhav Ashwini , Gupta Kriti , Ninawe Pranay , Ballav Nirmalya
Published: October 2019

In this work, we have synthesized nanocomposites made up of a metal–organic framework (MOF) and conducting polymers by polymerization of specialty monomers such as pyrrole (Py) and 3,4‐ethylenedioxythiophene (EDOT) in the voids of a stable and biporous Zr‐based MOF (UiO‐66). FTIR and Raman data confirmed the presence of polypyrrole (PPy) and poly3,4‐ethylenedioxythiophene (PEDOT) in UiO‐66‐PPy and UiO‐66‐PEDOT nanocomposites, respectively, and PXRD data revealed successful retention of the structure of the MOF. HRTEM images showed successful incorporation of polymer fibers inside the voids of the framework. Owing to the intrinsic biporosity of UiO‐66, polymer chains were observed to selectively occupy only one of the voids. This resulted in a remarkable enhancement (million‐fold) of the electrical conductivity while the nanocomposites retain 60–70 % of the porosity of the original MOF. These semiconducting yet significantly porous MOF nanocomposite systems exhibited ultralow thermal conductivity. Enhanced electrical conductivity with lowered thermal conductivity could qualify such MOF nanocomposites for thermoelectric applications.
Robust Synthesis of Gold‐Based Multishell Structures as Plasmonic Catalysts for Selective Hydrogenation of 4‐Nitrostyrene
Authors: Li Jian , Long Yan , Liu Yu , Zhang Lingling , Wang Qishun , Wang Xiao , Song Shuyan , Zhang Hongjie
Published: October 2019

A robust self‐template strategy is used for facile and large‐scale synthesis of porous multishell gold with controllable shell number, sphere size, and in situ surface modification. The process involved the rapid reduction of novel Au‐melamine colloidal templates with a great amount of NaBH4in presence of poly(sodium‐p‐styrenesulfonate) (PSS). After soaking the templates in other metal salt solution, the obtained bimetallic templates could also be generally converted into bimetallic multishell structures by same reduction process. In the hydrogenation of 4‐nitrostyrene using NH3BH3as a reducing agent, the porous triple‐shell Au with surface modification (S‐PTSAu) exhibited excellent selectivity (97 %) for 4‐aminostyrene in contrast with unmodified triple‐shell Au. Furthermore, it also showed higher enhancement of catalytic activity under irradiation of visible light as compared to similar catalysts with fewer shells.
Bridge‐Clamp Bis(tetrazine)s with [N]8 π‐Stacking Interactions and Azido‐s‐Aryl Tetrazines: Two Classes of Doubly Clickable Tetrazines
Authors: Mboyi Clève D. , Vivier Delphine , Daher Ahmad , Fleurat‐Lessard Paul , Cattey Hélène , Devillers Charles H. , Bernhard Claire , Denat Franck , Roger Julien , Hierso Jean‐Cyrille
Published: October 2019

Click chemistry at a tetrazine core is useful for bioorthogonal labeling and crosslinking. Introduced here are two new classes of doubly clickable s‐aryl tetrazines synthesized by Cu‐catalyzed cross‐coupling. Homocoupling of o‐brominated s‐aryl tetrazines leads to bis(tetrazine)s structurally characterized by tetrazine cores arranged face‐to‐face. [N]8 π‐stacking interactions are essential to the conformation. Upon inverse electron demand Diels–Alder (iEDDA) cycloaddition, the bis(tetrazine)s produce a unique staple structure. The o‐azidation of s‐aryl tetrazines introduces a second proximal intermolecular clickable function that leads to double click chemistry opportunities. The stepwise introduction of fluorophores and then iEDDA cycloaddition, including bioconjugation to antibodies, was achieved on this class of tetrazines. This method extends to (thio)etherification, phosphination, trifluoromethylation and the introduction of various bioactive nitrogen‐based heterocycles.
Visible‐Light‐Induced ortho‐Selective Migration on Pyridyl Ring: Trifluoromethylative Pyridylation of Unactivated Alkenes
Authors: Jeon Jinwon , He Yu‐Tao , Shin Sanghoon , Hong Sungwoo
Published: October 2019

The photocatalyzed ortho‐selective migration on a pyridyl ring has been achieved for the site‐selective trifluoromethylative pyridylation of unactivated alkenes. The overall process is initiated by the selective addition of a CF3 radical to the alkene to provide a nucleophilic alkyl radical intermediate, which enables an intramolecular endo addition exclusively to the ortho‐position of the pyridinium salt. Both secondary and tertiary alkyl radicals are well‐suited for addition to the C2‐position of pyridinium salts to ultimately provide synthetically valuable C2‐fluoroalkyl functionalized pyridines. Moreover, the method was successfully applied to the reaction with P‐centered radicals. The utility of this transformation was further demonstrated by the late‐stage functionalization of complex bioactive molecules.
Functional dopaminergic neurons derived from human chorionic mesenchymal stem cells ameliorate striatal atrophy and improve behavioral deficits in Parkinsonian rat model
Authors: Ebrahimi Vahid , Eskandarian Boroujeni Mahdi , Aliaghaei Abbas , Abdollahifar Mohammad Amin , Piryaei Abbas , Haghir Hossein , Sadeghi Yousef
Published: October 2019

Human chorionic mesenchymal stem cells (HCMSCs) have been recognized as a desirable choice for cell therapy in neurological disorders such as Parkinson's disease (PD). Due to invaluable features of HCMSCs including their immunomodulatory and immunosuppressive properties, easily accessible and less differentiated compared to other types of MSCs, HCMSCs provide a great hope for regenerative medicine. Thus, the purpose of this study was to determine the in vitro and in vivo efficacy of HCMSCs‐derived dopaminergic (DA) neuron‐like cells with regard to PD. Initially, HCMSCs were isolated and underwent a 2‐week DA differentiation, followed by in vitro assessments, using quantitative real‐time polymerase chain reaction, immunocytochemistry, patch clamp recording, and high‐performance liquid chromatography. In addition, the effects of implanted HCMSCs‐derived DA neuron‐like cells on the motor coordination along with stereological alterations in the striatum of rat models of PD were investigated. Our results showed that under neuronal induction, HCMSCs revealed neuron‐like morphology, and expressed neuronal and DA‐specific genes, together with DA release. Furthermore, transplantation of HCMSCs‐derived DA neurons into the striatum of rat models of PD, augmented performance. Besides, it prevented reduction of striatal volume, dendritic length, and the total number of neurons, coupled with a diminished level of cleaved caspase‐3. Altogether, these findings suggest that HCMSCs could be considered as an attractive strategy for cell‐based therapies in PD.
Optimization of factors influencing enzyme activity and product selectivity and the role of proton transfer in the catalytic mechanism of patchoulol synthase
Authors: Ekramzadeh Kimia , Brämer Chantal , Frister Thore , Fohrer Jörg , Kirschning Andreas , Scheper Thomas , Beutel Sascha
Published: October 2019

The patchoulol synthase (PTS) from Pogostemon cablin is a versatile sesquiterpene synthase and produces more than 20 valuable sesquiterpenes by conversion of the natural substrate farnesyl pyrophosphate (FPP). PTS has the potential to be used as a biocatalyst for the production of valuable sesquiterpenes such as (−)‐patchoulol. The objective of the present study is to develop an efficient biotransformation and to characterize the biocatalytic mechanism of the PTS in detail. For this purpose, soluble PTS was prepared using an optimized cultivation protocol and continuous downstream process with a purity of 98%. The PTS biotransformation was then optimized regarding buffer composition, pH‐value, and temperature for biotransformation as well as functional and kinetic properties to improve productivity. For the bioconversion of FPP, the highest enzyme activity was reached with the 2‐(N‐morphlino)ethanesulfonic acid (MES) buffer containing 10% (v/v) glycerol and 10 mM MgCl2 at pH 6.4 and 34°C. The PTS showed an unusual substrate inhibition for sesquiterpene synthases indicating an intermediate sesquiterpene formed in the active center. Deuteration experiments were used to gain further insights into the biocatalytic mechanism described in literature. Thus it could be shown that a second substrate binding site must be responsible for substrate inhibition and that further protonation and deprotonation steps are involved in the reaction mechanism.
HOTAIR‐induced apoptosis is mediated by sponging miR‐130a‐3p to repress chondrocyte autophagy in knee osteoarthritis
Authors: He Bin , Jiang Dianming
Published: October 2019

Knee osteoarthritis (KOA) is a multifactorial disease characterized by the loss of articular cartilage. Hox transcript antisense intergenic RNA (HOTAIR) long non‐coding RNA (lncRNA) is highly expressed in some cases of OA; however, its role in chondrocyte apoptosis in KOA and the mechanism by which HOTAIR mediates apoptosis in chondrocytes are not completely understood. Here, we evaluated the effects of HOTAIR on chondrocyte apoptosis in KOA. Our results showed that HOTAIR expression was significantly upregulated in cartilage tissues located at the femoral condyles or tibial plateaus of OA resection regions when compared with control regions in patients with normal non‐weight‐bearing area femoral condyle articular cartilage. Overexpression of HOTAIR caused a sharp increase in apoptosis rates and a reduction in the viability of chondrocytes. These effects were accompanied by the upregulation of Bax expression and the proteolytic cleavage of caspase 3 expression and downregulation of survivin and Bcl‐2 expression. The silencing of HOTAIR produced the opposite effects. Moreover, the cartilaginous expression of miR‐130a‐3p was notably reduced in the OA resection regions of KOA patients. Luciferase assays showed that HOTAIR‐adsorbed and reduced the levels of miR‐130a‐3p in chondrocytes. Further, inhibition of miR‐130a‐3p remarkably promoted the apoptosis of chondrocytes and repressed cell growth, while the silencing of HOTAIR could rescue the apoptosis mediated by miR‐130a‐3p inhibition. Chondrocyte autophagy was suppressed in a HOTAIR‐dependent, miR‐130a‐3p inhibitor‐mediated manner. Overall, our data revealed that aberrantly high expression of HOTAIR resulted in massive apoptosis events caused by the sponging of miR‐130a‐3p to suppress autophagy in chondrocytes, which, in turn, might trigger KOA. Therefore, inhibition of HOTAIR‐mediated apoptosis might be a potential mechanism that can be targeted by gene therapy of KOA.
Ensure due process in disciplinary actions involving students with disabilities
Authors: Charmatz Marc
Published: October 2019

The legal issues discussed by the United States Court of Appeals for the Sixth Circuit in Endres v. Northeast Ohio Medical University, No. 18‐3825 (6th Cir. 08/30/19) may seem mundane — the statute of limitations and qualified immunity from monetary damages — but the facts as recited by the appeals court offer a wealth of do's and don'ts for colleges and universities.
Counteract sleep‐loss misperceptions of college students with disabilities
Authors: Bedrossian Louise
Published: October 2019

A survey by the Centers for Disease Control and Prevention showed that about 7–19% of adults in America report insufficient sleep. Adequate sleep is essential for both physical and mental health, safety, and quality of life. Conditions such as high blood pressure, heart and kidney disease, diabetes, stroke, obesity, and depression are linked to sleep deficiency, as are certain mental health conditions.
Program for visually impaired builds skills, self‐awareness
Authors: Enos Gary
Published: October 2019

The College Success@Perkins program assists blind and visually impaired students in skill building and self‐discovery to prepare them for college, or whatever path they ultimately pursue. Leslie Thatcher, Director of the program at the Perkins School for the Blind in Massachusetts, discussed the components that equip blind students at a pivotal time for their growth.
Meta‐analysis on the efficacy and safety of SGLT2 inhibitors and incretin based agents combination therapy vs. SGLT2i alone or add‐on to metformin in type 2 diabetes
Authors: Zhou Yue , Geng Zhuang , Wang Xiang , Huang Yajing , Shen Liyan , Wang Yangang
Published: October 2019

We aimed to determine whether sodium‐glucose cotransporter type 2 inhibitors (SGLT2is) and incretin‐based agents combination therapy produces more benefits than SGLT2is alone in patients with type 2 diabetes mellitus (T2DM). PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing SGLT2is plus Dipeptidyl‐Peptidase 4 inhibitors (SGLT2is/DPP4is) or glucagon like peptide‐1 receptor agonists (SGLT2is/GLP‐1RAs) against SGLT2is as monotherapy or add‐on to metformin in T2DMs. A total of 13 studies with 7350 participants were included. Combination with GLP‐1RAs exhibited more HbA1c reduction (WMD: −0.8; 95% CI, −1.14 to −0.45%), weight loss (−1.46; 95% CI, −2.38 to −0.54 kg), and systolic blood pressure (SBP) reduction (−2.88; 95% CI, −4.52 to −1.25 mmHg) versus SGLT2is alone but increased the gastrointestinal disorder risk (RR: 1.68; 95% CI, 1.14‐2.47). Combination with DPP4is exhibited an extra effect on HbA1c reduction (−0.47; 95% CI, −0.58 to −0.37%), a neutral effect on weight (0.19; 95% CI, −0.11 to 0.48 kg) and SBP (−0.01; 95% CI, −0.85 to 0.63 mmHg), and ameliorated the genital infections risk (0.73; 95% CI, 0.54‐0.97) versus SGLT2is. Meta‐regression indicated the hypoglycemic efficacy of SGLT2is/DPP4is is higher in Asians than in other ethnics, and the differences in BMI across ethnic groups may mediate this effect. SGLT2is and incretin‐based agents combination therapy is efficacious and safe versus SGLT2is alone in T2DMs. Particularly, combination with GLP‐1RAs shows additional benefits to glycemic, weight, and SBP control to a larger extent than DPP4is, while combination with DPP4is ameliorates the risk for genital infection seen with SGLT2is. We highlight the need for individualized treatment related to the selection of this novel combination therapy.
Genetic diversity and differentiation of Daphnia galeata in the middle and lower reaches of the Yangtze River, China
Authors: Liu Qi , Deng Daogui , Zhang Kun , He Ping , Sun Yuchen , Zhang Tingting , Yang Wei , Liu Wei
Published: October 2019

Mitochondrial 16S rDNA and CO I gene were used as molecular markers for the analysis of the genetic diversity and differentiation of Daphnia galeata populations in nine water bodies in the middle and lower reaches of the Yangtze River. In the combined 16S rDNA and CO I gene sequences, 54 variable sites and 44 haplotypes were observed among 219 individuals belonging to nine D. galeata populations. Average haplotype diversity and nucleotide diversity were, respectively, 0.72% and 0.56%. The F‐statistics (FST) value of the D. galeata populations was 0.149. According to the results of the neutral test, D. galeata in the middle and lower reaches of the Yangtze River had experienced a bottleneck effect in the history. Molecular variance analysis indicated that the genetic differentiation of the D. galeata populations mainly occurred within populations (85.09%). Greater genetic differentiations of D. galeata among individuals within populations appeared in the populations from the Huaihe River basin, whereas smaller genetic differentiations occurred in the populations from the middle reaches of the Yangtze River. Strong gene flows were all observed between Group I (four populations from the middle reaches of the Yangtze River) and Group ΙΙ (three populations from the middle and lower reaches of the Yangtze River), and Group ΙΙΙ (two populations from the Huaihe River basin). The effective migration rates (M) were 851.49 from Group I to Group ΙΙ and 685.96 from Group I to Group ΙΙΙ, respectively. However, no significant relationship was observed between the genetic differentiation and geographical distance of the nine populations (r = .137, p > .05). Results suggested that the genetic differentiation of D. galeata in the water bodies in the middle and lower reaches of the Yangtze River resulted mainly from geographical isolation.
Pressure‐Enhanced C–H Bond Activation in Chloromethane Platinum(II) Complexes
Authors: Schmitz Dominik , Kalter Marcel , Dunbar Andrew C. , Vöst Marcel , Fischer Andreas , Batke Kilian , Eickerling Georg , Ruhland Klaus , Ebad‐Allah Jihaan , Kuntscher Christine , Scherer Wolfgang
Published: October 2019

The nature of the interaction between chloromethanes CH4–nClnand Pt(II) complexes has been studied by high‐pressure X‐ray diffraction and infrared spectroscopy in combination with DFT calculations. In case of electron rich complexes such as d8‐Pt(btz‐N,N′)(phenyl)LwithL= phenyl, Cl, Br and btz = 2,2′‐Bi‐5,6‐dihydro‐4H‐1,3‐thiazine stable chloroform adducts with bridging hydrogen atoms in the η1(C–H)Pt moieties were isolated which display highly activated C–H bonds. This activation is a consequence of a pronounced Pt(dz²)→σ*(C–H) back donation and is signaled by large red‐shifts of the isolatedνis(C–H) stretching modes. The extent of the C–H bond activation and covalent Pt–H bond formation in the η1(C–H)Pt moieties is thereby controlled by (i) the σ/π donor capabilities of the ligandsL, (ii) the orientation of the coordinating C–H bond with regard to the Pt(dz²) orbital and (iii) the applied pressure.
Functionalization of PEO layer formed on Ti‐15Mo for biomedical application
Authors: Leśniak Katarzyna , Płonka Joanna , Śmiga‐Matuszowicz Monika , Brzychczy‐Włoch Monika , Kazek‐Kęsik Alicja
Published: October 2019

In the present work, deposition of poly(sebacic anhydride) PSBA loaded by amoxicillin, cefazolin, or vancomycin on a previously anodized Ti‐15Mo surface is presented. PSBA loaded by the drug was deposited so as not to lose the functionality of the porous oxide layer microstructure. The morphology was evaluated using scanning electron microscopy, surface roughness, and wettability. The drug concentration was evaluated using high‐performance liquid chromatography. It was determined that the drugs were loaded into coatings in the range of 35.2–122.87 μg/cm2 of Ti sample. The drugs released more than 16% after 0.5 hr of the hybrid coating immersion in artificial saliva. After 3 days, the PSBA coatings were degraded by 51.3 mol %, and after 7 days by 77.8 mol %, which makes it possible to load the material by different, biologically active substances. An antimicrobial investigation of Staphylococcus aureus (DSM 24167) and Staphylococcus epidermidis (ATCC 700296) confirmed the activity of the hybrid layers against the pathogens. Hybrid layer with vancomycin best inhibits the adhesion of the bacteria, whereas coatings with amoxicillin and cefazolin showed a much better bactericidal activity. In this article, the difference in the obtained results is discussed, as well as the possibility of the application of this functional material in biomedicine.
Manganese‐doped green tea‐derived carbon quantum dots as a targeted dual imaging and photodynamic therapy platform
Authors: Irmania Novi , Dehvari Khalilalrahman , Gedda Gangaraju , Tseng Po‐Jen , Chang Jia‐Yaw
Published: October 2019

In this work, manganese‐doped carbon quantum dots (Mn‐CQDs) have been synthesized through a one‐pot hydrothermal method by using waste green tea. The Mn2+ dopants were introduced to impart magnetic resonance capability. Upon optimization of the experimental conditions, magnetofluorescent Mn‐CQDs exhibit an excitation‐dependent blue emission. The abundant functional groups on Mn‐CQDs not only promote water solubility but also allow straightforward functionalization with amine groups. The amine‐terminated Mn‐CQDs were then subsequently conjugated to folic acid (FA) and chlorin e6 (Ce6) to obtain the Mn‐CQDs@FA/Ce6 magnetofluorescent photodynamic therapy (PDT) agent. in vitro studies using three different cells indicated specific targeting of Mn‐CQDs@FA/Ce6 to the overexpressing folate receptor human epithelial carcinoma cell line (HeLa) cancer cells. Furthermore, Mn‐CQDs@FA/Ce6 enhanced magnetic resonance imaging (MRI) signal with an r2/r1 ratio of 5.77. Favorably, by using the Mn‐CQDs@FA delivery system, active Ce6 can reach the cellular interior while its red fluorescence (FL) and reactive oxygen species generation can be retained, as has been verified by confocal microscopy. in vitro cell viability studies verified the biocompatibility of Mn‐CQDs@FA/Ce6 nanohybrid with no significant toxicity up to 500 ppm while PDT treatment with 5 min irradiation (671 nm, 1 W cm−2) was effective in killing >90% of cells. The light‐triggered Mn‐CQDs@FA/Ce6 multifunctional hybrid can serve as a dual‐modal FL/MRI probe and as an efficient PDT agent to detect and eradicate cancer cells remotely.
Analysis of competing endogenous RNA network identifies a poorly differentiated cancer‐specific RNA signature for hepatocellular carcinoma
Authors: Chen Qi‐Feng , Huang Tao , Si‐Tu Qi‐Jiao , Wu Peihong , Shen Lujun , Li Wang , Huang Zilin
Published: October 2019

Plenty of evidence has suggested that long noncoding RNAs (lncRNAs) play a vital role in competing endogenous RNA (ceRNA) networks. Poorly differentiated hepatocellular carcinoma (PDHCC) is a malignant phenotype. This paper aimed to explore the effect and the underlying regulatory mechanism of lncRNAs on PDHCC as a kind of ceRNA. Additionally, prognosis prediction was assessed. A total of 943 messenger RNAs (mRNAs), 86 miRNAs, and 468 lncRNAs that were differentially expressed between 137 PDHCCs and 235 well‐differentiated HCCs were identified. Thereafter, a ceRNA network related to the dysregulated lncRNAs was established according to bioinformatic analysis and included 29 lncRNAs, 9 miRNAs, and 96 mRNAs. RNA‐related overall survival (OS) curves were determined using the Kaplan‐Meier method. The lncRNA ARHGEF7‐AS2 was markedly correlated with OS in HCC (P = .041). Moreover, Cox regression analysis revealed that patients with low ARHGEF7‐AS2 expression were associated with notably shorter survival time (P = .038). In addition, the area under the curve values of the lncRNA signature for 1‐, 3‐, and 5‐year survival were 0.806, 0.741, and 0.701, respectively. Furthermore, a lncRNA nomogram was established, and the C‐index of the internal validation was 0.717. In vitro experiments were performed to demonstrate that silencing ARHGEF7‐AS2 expression significantly promoted HCC cell proliferation and migration. Taken together, our findings shed more light on the ceRNA network related to lncRNAs in PDHCC, and ARHGEF7‐AS2 may be used as an independent biomarker to predict the prognosis of HCC.
MicroRNA‐16 is involved in the pathogenesis of pre‐eclampsia via regulation of Notch2
Authors: Yuan Yuan , Wang Xiaoying , Sun Qiuyu , Dai Xu , Cai Yan
Published: October 2019

In recent years, the role of microRNAs (miRNAs) in pre‐eclampsia (PE) has been demonstrated, while the relevant mechanisms of miR‐16 in PE await to be unearthed. Thus, the aim of this study is to explore whether miR‐16 exerts its function in PE, and we assumed that miR‐16 may be implicated in the occurrence of PE by adjusting the biological functions of trophoblast cells via modulating Notch2. Placental tissues of pregnant women with normal pregnancy and PE were collected to detect the expression of miR‐16, Notch2, and Notch3. The effects of miR‐16 and Notch2 on the biological functions of BeWo and JEG‐3 cells were further determined. Expression of miR‐16 and Notch2 in trophoblast cells was detected by reverse transcription quantitative polymerase chain reaction and western blot assay. Downregulated Notch2 and upregulated miR‐16 and Notch3 were found in placental tissues of PE. There was a negative correlation between Notch2 and miR‐16 expression (r = −0.769), and a positive correlation between Notch3 and miR‐16 expression (r = 0.676; p < .05). Overexpression of miR‐16 inhibited proliferation, migration, and invasion, and facilitated the apoptosis of BeWo and JEG‐3 cells, but overexpression of Notch2 reversed this trend. Overexpression of miR‐16 inhibited Notch2 expression in BeWo and JEG‐3 cells, and Notch2 was the target gene of miR‐16. Our study highlights that overexpression of miR‐16 is involved in PE by regulating the biological functions of trophoblast cells via inhibition of Notch2. This paper provides a new idea for further study of the pathogenesis of PE.
Circular RNA circ_0074026 indicates unfavorable prognosis for patients with glioma and facilitates oncogenesis of tumor cells by targeting miR‐1304 to modulate ERBB4 expression
Authors: Chen Minghui , Liu Xiaojuan , Xie Peng , Wang Pengyu , Liu Mingli , Zhan Yongxuan , Wang Hongjun , Feng Yan , Li Yongli
Published: October 2019

Glioma (GM) is a common malignancy all over the world. A novel circular RNA (circRNA), circ_0074026, has been documented to be upregulated in GM tissues than that of normal counterparts, as confirmed by circRNA microarray. However, the biological mechanism of circ_0074026 is still unreported in GM. The expression of circ_0074026 in GM specimens or cells was detected by quantitative real‐time polymerase chain reaction. Fisher's exact test was utilized to evaluate the clinical relevance of circ_0074026 in patients with GM. Kaplan–Meier and Cox regression analysis were used to estimate the prognostic value of circ_0074026. Cell counting kit‐8 (CCK‐8), acridine orange/ethidium bromide double fluorescence staining, flow cytometry, wound healing, and Transwell assays were used to detect the malignant behaviors of GM cells including cell growth, apoptosis, migration, and invasion. CCK‐8 and flow cytometric experiments were utilized to evaluate whether circ_0074026 had a side effect on normal human astrocyte cells. The interaction between miR‐1304 and circ_0074026 or ERBB4 3′‐untranslated region (3′‐UTR) was predicted with circular RNA Interactome and TargetScan, respectively, and then confirmed by the dual‐luciferase reporter test. The levels of circ_0074026 were both apparently increased in GM samples and cells. The elevated expression of circ_0074026 was linked to patients’ tumor size, WHO grade, disease‐free survival, and overall survival. The depletion of circ_0074026 can block cell growth, migration, invasion, and impel cell apoptosis in the LN229 cell line. However, ectopically expressed circ_0074026 caused the opposite effect in the U251 cell line. The following dual‐luciferase reporter assay demonstrated that miR‐1304 interacted with circ_0074026 and ERBB4 3′‐UTR. Furthermore, the rescue assay indicated that circ_0074026 modulated ERBB4 to promote tumor progression by regulating miR‐1304. Thus, a novel regulatory pathway may provide a new therapeutic target for patients with GM.
YAP1 inhibits the induction of TNF‐α‐stimulated bone‐resorbing mediators by suppressing the NF‐κB signaling pathway in MC3T3‐E1 cells
Authors: Yang Beining , Sun Hualing , Xu Xiaoxiao , Zhong Heli , Wu Yanru , Wang Jiawei
Published: October 2019

Yes‐associated protein 1 (YAP1), the core downstream effector of the Hippo signaling cascade, was involved in the regulation of osteoblast and osteoclast differentiation and in bone metabolism. However, the regulatory effects and mechanisms of YAP1 on bone‐remodeling molecules in osteoblasts under inflammation remain unknown. In this study, YAP1 expression level was downregulated after treatment with inflammatory cytokine tumor necrosis factor‐α (TNF‐α) in MC3T3‐E1 cells. The key osteoclastogenic molecules induced by TNF‐α, namely, interleukin‐6 and receptor activator of nuclear factor‐κB (NF‐κB) ligand, were suppressed after lentivirus‐induced YAP1 overexpression, which dramatically increased the expression level of osteoprotegerin. Conversely, the expression levels of the above factors showed opposite trends in the YAP1 small interfering RNA and YAP1 inhibitor (verteporfin) group. Mechanistically, YAP1 attenuated the TNF‐α‐induced activation of the NF‐κB signaling pathway as revealed by the reduced expression of phosphorylated‐p65 and NF‐κB reporter activity and the nuclear translocation of p65. Moreover, the expression level of YAP1 suppressed by TNF‐α was reversed by berberine in concentration‐dependent manner. Taken together, our study suggests that YAP1 plays a critical role in the regulation of bone metabolism and is a potential therapeutic target for treating inflammatory bone resorption.
BZW2 promotes the malignant progression of colorectal cancer via activating the ERK/MAPK pathway
Authors: Huang Longping , Chen Si , Fan Haijun , Ai Fan , Sheng Weiwei
Published: October 2019

Colorectal cancer (CRC) is one of the most prevalent malignant solid cancers worldwide involving the dysregulation of multiple signaling molecules. However, the role and corresponding mechanism of basic leucine zipper and W2 domains 2 (BZW2) in CRC development, to our knowledge, has not been reported. We found BZW2 was overexpressed in human CRC tissues compared with that in paired adjacent colorectal samples. BZW2 overexpression was closely associated with tumor T stage (p = .030), metastatic lymph nodes (p = .037), TNM stage (p = .018) and the worse prognosis of CRC patients (p = .009). Moreover, BZW2 was an independent disadvantage prognostic factor (p = .031). BZW2 also showed an increased expression in different invasive CRC cell lines. Its silencing and overexpression diminished and increased cell proliferation, invasion, and migration in Colo205 and HCT116 cells via specifically activating of extracellular‐signal‐regulated kinase (ERK)/mitogen‐activated protein kinase (MAPK) signaling. Moreover, ERK/MAPK inhibitor PD98059 reverse the enhancement of cell proliferation, invasion, and migration in BZW2 overexpressing HCT116 cells. BZW2 silencing also inhibited subcutaneous tumors growth and p‐ERK expression in vivo. BZW2 promotes the malignant progression of CRC via activating ERK/MAPK signaling, which provided a promising gene target therapy for CRC.
HotBalloon ablation of atrial fibrillation in patients with dextrocardia and situs inversus by “mirror image” approach
Authors: Miyauchi Shunsuke , Nakano Yukiko , Ikeuchi Yoshihiro , Okamura Sho , Okubo Yousaku , Hironobe Naoya , Tokuyama Takehito , Kihara Yasuki
Published: October 2019

A 51‐year‐old man with dextrocardia and complete situs inversus who presented with palpitation as a result of drug refractory paroxysmal atrial fibrillation (AF) was referred to our hospital for catheter ablation. Pulmonary vein isolation (PVI) was performed using the HotBalloon technique. We were able to accomplish AF ablation safely and easily using 180 degree‐inversed mirror images of X‐ray fluoroscopy. We have reported successful PVI for AF with dextrocardia using HotBalloon and mirror image of X‐ray fluoroscopy without any complication for the first time.
Starving the Gut: A Deficit of Butyrate in the Intestinal Ecosystem of Children With Intestinal Failure
Authors: Dowhaniuk Jenna K. , Szamosi Jake , Chorlton Sam , Owens Jillian , Mileski Heather , Clause Rose‐Frances , Pernica Jeffrey M. , Bowdish Dawn M. E. , Surette Michael G. , Ratcliffe Elyanne M.
Published: October 2019

Background

Intestinal epithelial integrity is influenced by short‐chain fatty acids (SCFAs) and is of critical importance for children with intestinal failure (IF) given the known devastating infectious and gastrointestinal complications. The composition of the microbiome in IF represents an important variable in the physiology and prognosis of this disease.

Aim

We sought to compare the intestinal microbiome and SCFA concentration of children who require parenteral nutrition (PN) with that of children with short‐bowel syndrome (SBS) who have discontinued PN and with age‐matched controls, using high‐throughput sequencing to investigate host‐microbe interactions.

Methods

Fifty‐three samples were submitted over 6–15 months. Six children with SBS + IF submitted 34 samples, and 6 children with SBS with discontinued PN submitted 15 samples; these were compared with samples from 5 control children. Fecal samples were analyzed by 16S ribosomal RNA partial gene sequencing using the MiSeq Illumina sequencer. SCFAs were measured in stool samples by mass spectrometry.

Results

Butyrate quantity was near absent in children with IF compared with that in controls (median 0.37 nmol/mg vs 10.92 nmol/mg; P < .0001). Similarly, commensal anaerobes known to produce SCFA, including Ruminococcaceae and Lachnospiraceae, were reduced in those with SBS. SBS + IF enteric samples demonstrated a 168‐fold increase in the relative abundance of the Escherichia genus seemingly attributable to the species Escherichia coli.

Conclusion

The reduced relative abundance of butyrate‐producing Clostridia as well as decreased intestinal butyrate concentration in children with IF support further investigation in therapeutic options that target butyrate‐producing bacterial communities or butyrate supplementation.
Exploring the enablers and inhibitors of electric vehicle adoption intention from sellers' perspective in India: A view of the dual‐factor model
Authors: Shankar Amit , Kumari Pooja
Published: October 2019

The electric vehicle (EV) is a crucial innovation with the potential to lower greenhouse gas emissions and help reduce the causes of climate change. Despite their multiple benefits, EVs are selling lower numbers than would be expected, seeming to require more positive intent from their sellers to increase the pace of EV adoption. Hence, this study explores the enablers and inhibitors of EV adoption intention from the sellers' perspective using a dual‐factor model. The extended theory of planned behavior has been used to explore the enablers, whereas the status quo bias theory has been used to explore the inhibitors of EV adoption. The results indicate that attitude, subjective norm, perceived behavioral control, environmental concern, and perceived corporate social responsibility obligation have significant positive impacts on intention to adopt EVs. However, regret avoidance, inertia, perceived threat, and perceived value have significant impacts on the resistance to adopt EVs. This study enriches the literature related to intention and resistance to adopt green technology and also provides several suggestions to marketers for increasing the pace of EV adoption.
Synthesis of metallosupramolecular polymers incorporating cage silsesquioxanes in the main chains
Authors: Hashimoto Mari , Fujii Shunichi , Imoto Hiroaki , Naka Kensuke
Published: October 2019

We first time prepared main‐chain type cage octasilsesquioxane (T8) containing coordination polymers based on transition metal complexes with a bis‐Schiff base T8 ligand (bis‐SA‐T8), which was prepared from para‐bis(3‐aminopropyl)hexaisobutyl‐substituted T8 cage (bis‐T8) with salicylaldehyde. A mono‐Schiff base T8 ligand (SA‐T8) was prepared from 3‐aminopropylheptaisobutyl‐substituted T8 cage (mono‐T8) with salicylaldehyde. Coordination of bis‐SA‐T8 with Cu2+ and Zn2+ in a solution as well as the film state was confirmed by the d–d transition appearing as broad shoulder on the longer wavelength at around 600 nm and the fluorescence at around 440–470 nm, respectively. The resulting metallosupramolecular polymers gave optically transparent films in the visible region by a casting method. However, opaque green and whitish films were obtained in the case of the Cu2+ and Zn2+ complexes with SA‐T8, respectively. The thermal stabilities of the metallosupramolecular polymers were higher than those of the corresponding metal complexes of SA‐T8. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2260–2266
Symmetry‐Based Electron–Phonon Decoupling and Jahn–Teller Theorem Violation in Specific Crystalline Structures
Authors: Milošević Ivanka , Nikolić Božidar , Damnjanović Milan
Published: October 2019

There is a special class of crystalline structures which, in the first‐order perturbation theory, allow for the electronic system to be decoupled from the phonon degrees of freedom. Such systems and electronic states are identified on the basis of symmetry and group theory. To arise such electron–phonon decoupling, three general symmetry‐based conditions are to be satisfied. By giving clear formulation of these criteria, a recipe for engineering the configurations with electron–phonon coupling deficiency is presented. The Jahn–Teller theorem validity is also discussed and it is shown that breakdown of the theorem in any dimension is possible, that is, there are specific configurations of molecules, polymers, layers, and 3D crystals, whose total energy is optimized by hosting a ground electronic state that is orbitally degenerate.
Molecular Beam Epitaxy Growth and Characterization of Germanium‐Doped Cubic AlxGa1−xN
Authors: Deppe Michael , Henksmeier Tobias , Gerlach Jürgen W. , Reuter Dirk , As Donat J.
Published: October 2019

In cubic (c‐)GaN Ge has emerged as a promising alternative to Si for n‐type doping, offering the advantage of slightly improved electrical properties. Herein, a study on Ge doping of the ternary alloy c‐AlxGa1−xN is presented. Ge‐doped c‐AlxGa1−xN layers are grown by plasma‐assisted molecular beam epitaxy. In two sample series, both the Al mole fraction x and the doping level are varied. The incorporation of Ge is verified by time‐of‐flight secondary ion mass spectrometry. Ge incorporation and donor concentrations rise exponentially with increasing Ge cell temperature. A maximum donor concentration of 1.4 × 1020 cm−3 is achieved. While the incorporation of Ge is almost independent of x, incorporation of O, which acts as an unintentional donor, increases for higher x. Dislocation densities start increasing when doping levels of around 3 × 1019 cm−3 are exceeded. Also photoluminescence intensities begin to drop at these high doping levels. Optical emission of layers with x > 0.25 is found to originate from a defect level 0.9 eV below the indirect bandgap, which is not related to Ge. In the investigated range 0 ≤ x ≤ 0.6, Ge is a suitable donor in c‐AlxGa1−xN up to the low 1019 cm−3 range.
An exact test for comparing two predictive values in small‐size clinical trials
Authors: Takahashi Kanae , Yamamoto Kouji
Published: October 2019

Positive and negative predictive values describe the performance of a diagnostic test. There are several methods to test the equality of predictive values in paired designs. However, these methods were premised on large sample theory, and they may not be suitable for small‐size clinical trials because of inflation of the type 1 error rate. In this study, we propose an exact test to control the type 1 error rate strictly for conducting a small‐size clinical trial that investigates the equality of predictive values in paired designs. In addition, we execute simulation studies to evaluate the performance of the proposed exact test and existing methods in small‐size clinical trials. The proposed test can calculate the exact P value, and as a result of simulations, the empirical type 1 error rate for the proposed test did not exceed the significance level regardless of the setting, and the empirical power for the proposed test is not much different from the other methods based on large‐sample theory. Therefore, it is considered that the proposed exact test is useful when the type 1 error rate needs to be controlled strictly.
Passive blockholders, informational efficiency of prices, and firm value
Authors: Chung Kee H. , Lee Choonsik , Shen Carl Hsin‐han
Published: October 2019

This paper analyzes the role of passive blockholders in corporate governance using data on Schedule 13G filings. We show that firm value increases with the number and aggregate ownership of passive blockholders after controlling for other possible determinants of firm value. More importantly, we show that the informational efficiency of prices (IEP) increases with the number and aggregate ownership of passive blockholders, and IEP is a channel through which passive blockholders affect firm value. Overall, our results suggest that managers perform better when stock prices reflect the economic consequences of their actions promptly and accurately through information‐based trading of blockholders.
Nested saturation control of multiple vector integrators and its application to motion control of UAVs
Authors: Xie Hui , Veitch Darryl
Published: October 2019

This paper presents two nested input saturation control schemes for a special class of multiple vector integrators with bounded additive disturbances. The considered systems originate from the motion control of rotary‐wing unmanned aerial vehicles (UAVs). The first scheme is based on a feedforward form, which requires state transformation and can be applied to stabilize arbitrary order vector integrator systems. The second scheme is constructed with original state variables using a new approach, applied here to double vector integrator systems. The capability of handling external disturbance using the two schemes is also analyzed. The two schemes are applied to design motion controllers for rotary‐wing UAVs and simulation results are provided to show the performances of two controllers.
A novel redesign framework to extend the application scope of a class of disturbance‐rejection algorithms
Authors: Yang Hao , Pei Hailong
Published: October 2019

In this paper, a novel redesign method is developed for a class of disturbance‐rejection algorithms so that they can be applied to pure‐feedback nonaffine‐in‐control nonlinear systems with matched and mismatched disturbances. First, a series of augmented dynamical equations, which evolve faster than the original system, are constructed to establish a boundary‐layer subsystem to derive the virtual and actual inputs for the nominal system. Then, the composite interconnected system is studied in the standard singular perturbed form. In the slow timescale, the reduced slow subsystem (RSS) is transformed into the chain of integrators form in the error coordinate, for which the existing antidisturbance methods can be employed. The tracking performance of the closed‐loop system is approximated by RSS under singular perturbation theory. The proposed redesign method is adopted to three existing disturbance‐rejection algorithms for a pure‐feedback nonaffine‐in‐control numerical example in the presence of matched and mismatched disturbances. The effectiveness is demonstrated by simulation experimental results.