bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal‐Treatment‐Induced Cu−Sn Core/Shell Nanowire Array Catalysts for Highly Efficient CO2 Electroreduction
Authors: Hu Hanjun , Wang Yutian , Du Nian , Sun Yufan , Tang Yang , Hu Qing , Wan Pingyu , Dai Liming , Fisher Adrian C. , Yang Xiao Jin
Published: October 2018

Hierarchical Cu−Sn core/shell nanowire arrays were built on 3‐dimensional macroporous Ni foams through a two‐step deposition, annealing, and electroreduction treatment. Cu was electroplated on Ni foam substrates and the sample was annealed at 500 °C followed by electroreduction, producing Cu nanowires of 150 nm diameter in arrays on the skeleton of Ni foams. Sn nanoparticles of 14–80 nm were then chemically deposited on Cu nanowires in clusters and a second annealing treatment at 200 °C followed by electroreduction re‐organized the clusters into a SnxO/Sn shell of 8 nm thickness. Creating such a Sn shell on Cu nanowires suppressed faradaic efficiencies for H2 evolution from 55.7 to 10.1 % and for HCOOH formation from 13.2 to 2.0 % and enhanced CO generation from 32.0 to 90.0 % at an applied potential of −0.8 V (vs. RHE). The faradaic efficiency for CO production remained almost constant at 90.0–91.4 % with total current densities of −13.2 to −19.3 mA cm−2 between −0.8 and −1.2 V (vs. RHE).
Ring‐Opening Polymerisation of Low‐Strain Nickelocenophanes: Synthesis and Magnetic Properties of Polynickelocenes with Carbon and Silicon Main Chain Spacers
Authors: Hailes Rebekah L. N. , Musgrave Rebecca A. , Kilpatrick Alexander F. R. , Russell Andrew D. , Whittell George R. , O'Hare Dermot , Manners Ian
Published: October 2018

Polymetallocenes based on ferrocene, and to a lesser extent cobaltocene, have been well‐studied, whereas analogous systems based on nickelocene are virtually unexplored. It has been previously shown that poly(nickelocenylpropylene) [Ni(η5‐C5H4)2(CH2)3]n is formed as a mixture of cyclic (6x) and linear (7) components by the reversible ring‐opening polymerisation (ROP) of tricarba[3]nickelocenophane [Ni(η5‐C5H4)2(CH2)3] (5). Herein the generality of this approach to main‐chain polynickelocenes is demonstrated and the ROP of tetracarba[4]nickelocenophane [Ni(η5‐C5H4)2(CH2)4] (8), and disila[2]nickelocenophane [Ni(η5‐C5H4)2(SiMe2)2] (12) is described, to yield predominantly insoluble homopolymers poly(nickelocenylbutylene) [Ni(η5‐C5H4)2(CH2)4]n (13) and poly(tetramethyldisilylnickelocene) [Ni(η5‐C5H4)2(SiMe2)2]n (14), respectively. The ROP of 8 and 12 was also found to be reversible at elevated temperature. To access soluble high molar mass materials, copolymerisations of 5, 8, and 12 were performed. Superconducting quantum interference device (SQUID) magnetometry measurements of 13 and 14 indicated that these homopolymers behave as simple paramagnets at temperatures greater than 50 K, with significant antiferromagnetic coupling that is notably larger in carbon‐bridged 6x/7 and 13 compared to the disilyl‐bridged 14. However, the behaviour of these polynickelocenes deviates substantially from the Curie–Weiss law at low temperatures due to considerable zero‐field splitting.
Electrochemical Reduction of N2 to NH3 at Low Potential by a Molecular Aluminum Complex
Authors: Sherbow Tobias J. , Thompson Emily J. , Arnold Amela , Sayler Richard I. , Britt R. David , Berben Louise A.
Published: October 2018

Electrochemical generation of ammonia (NH3) from nitrogen (N2) using renewable electricity is a desirable alternative to current NH3 production methods, which consume roughly 1 % of the world's total energy use. The use of catalysts to manipulate the required electron and proton transfer reactions with low energy input is also a chemical challenge that requires development of fundamental reaction pathways. This work presents an approach to the electrochemical reduction of N2 into NH3 using a coordination complex of aluminum(III), which facilitates NH3 production at −1.16 V vs. SCE. Reactions performed under 15N2 liberate 15NH3. Electron paramagnetic resonance spectroscopic characterization of a reduced intermediate and investigations of product inhibition, which limit the reaction to sub‐stoichiometric, are also presented.
Analysis of Mitochondrial Dimensions and Cristae Structure in Pluripotent Stem Cells Using Transmission Electron Microscopy
Authors: Tobias I. C. , Khazaee R. , Betts D. H.
Published: October 2018

Dynamic alterations to mitochondrial structure and function regulate cell fate decisions and underlie multiple age‐related and genetic diseases that are modeled using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Transmission electron microscopy (TEM) can be used to obtain high‐resolution micrographs of mitochondria, but mitochondrial ultrastructure is easily distorted during specimen processing. This unit describes a method that preserves mitochondrial membrane structure from adherent ESC cultures for TEM sample preparation. This procedure is useful for assessing ultrastructural changes to mitochondria during differentiation, reprogramming, or experimental manipulation of ESC metabolism. We provide comprehensive protocols for: (1) preparation of ESC cultures for TEM; (2) retrieval of thin sections from individual ESCs; and (3) contrast staining and morphometric analysis of mitochondria and cristae. This unit also describes an alternative procedure for samples with low cell numbers and a supporting protocol for morphometric image analysis. Collectively, these protocols allow for the observation and quantitative analysis of mitochondria in ESCs. © 2018 by John Wiley & Sons, Inc.
Weighing of Evidence by Health Technology Assessment Bodies: Retrospective Study of Reimbursement Recommendations for Conditionally Approved Drugs
Authors: Vreman Rick A. , Bouvy Jacoline C. , Bloem Lourens T. , Hövels Anke M. , Mantel‐Teeuwisse Aukje K. , Leufkens Hubert G.M. , Goettsch Wim G.
Published: October 2018

This study assessed whether five Health Technology Assessment (HTA) bodies in Europe were more negative about drugs with a Conditional Marketing Authorization (CMA) that are approved without controlled studies compared to CMA drugs that are approved based on controlled studies. The HTA recommendations were categorized into positive, restricted, and negative. A total of 92 HTA recommendations were available for 27 drugs. Thirty of 62 (48%) and 17 of 30 (57%) of the recommendations were negative for drugs with and without controlled studies, respectively. Overall, only 12 (13%) recommendations were positive. In all jurisdictions, recommendations between drugs with and drugs without controlled data were comparable, which suggests that the presence of controlled data is not decisive in HTA evaluations. The small proportion of unrestricted positive recommendations highlights difficulties with recommending the drugs in this cohort, which may be caused by scientific uncertainty or other factors. Earlier collaboration between stakeholders is advised in order to improve patient access.
High false positive rate of white blood cells in urine samples of pregnant women may be caused by epithelial cells being misclassified by the sysmex UF‐1000i urine flow cytometer
Authors: Yang Wei , Yu Xiaochen , Liu Dan , Guan Xiuru
Published: October 2018

Background

The UF‐1000i has been widely used in screening urinary sediments. However, the interference factor of the UF‐1000i in the screening urinary sediments of pregnant women has not been reported. The aim of the study was to demonstrate that epithelial cells (ECs) cause a high false positive rate of white blood cells (WBCs) by the UF‐1000i in pregnant women.

Methods

Urine samples were collected from 207 pregnant women. All samples were measured by the UF‐1000i and a microscopic method.

Results

The areas under the curve (AUC) for WBC and EC counts were 0.837 (95% CI, 0.773–0.901) and 0.844 (95% CI, 0.785–0.903), respectively. The positive rates of the WBC and EC were 73.43% and 37.20%, respectively, by the UF‐1000i, and they were 19.32% and 72.95% by the microscopic method. The positive predictive value, negative predictive value, false positive rates, and false negative rates by the UF‐1000i were for WBC 25.66%, 98.18%, 74.34%, and 1.82%, respectively, and for EC they were 96.1%, 40.77%, 3.9%, and 59.23%, respectively. The coefficient of correlation R value was 0.503 (P < 0.01) between WBC by UF‐1000i and EC by the microscopic method in WBC false positive samples.

Conclusions

EC could be an interference factor for the UF‐1000i in screening urinary WBC of pregnant women, and the high false positive rate for WBC may be caused by ECs being misclassified as WBCs by the UF‐1000i. © 2018 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.
Synthesis, carbonic anhydrase inhibitory activity and antioxidant activity of some 1,3‐oxazine derivatives
Authors: Qamar Rabia , Saeed Aamer , Saeed Maria , Ashraf Zaman , Abbas Qamar , Hassan Mubashir , Albericio Fernando
Published: October 2018

Hit, Lead & Candidate Discovery

A series of 1‐(6‐methyl‐2‐substituted phenyl‐4‐thioxo‐4H‐1,3‐oxazin‐5‐yl)ethanones (3a‐n) were synthesized by the reaction of benzoyl isothiocyanates with active methylene compound acetylacetone in the presence of triethyl amine in a one‐pot process. The structures of the products were elucidated by elemental analyses, FT‐IR, 1H NMR, 13C NMR, and mass spectroscopy. These new 1,3‐oxazine derivatives were evaluated for their inhibitory activity against carbonic anhydrase II. Results for in vitro assay revealed that compound 3b having 4‐methoxy phenyl moiety was the most potent inhibitor with IC50 value of 0.144 ± 0.008 μM. It exhibited higher enzyme inhibitory activity as compared to the standard acetazolamide (IC50 = 0.997 ± 0.061 μM). The compounds 3c, 3h, and 3n also displayed superior inhibitory activities compared to the rest of the synthesized oxazine derivatives. The radical scavenging activity of oxazine derivatives was also performed and it was found that compounds showed moderate antioxidant activity. Lipinski rule confirmed the therapeutic potential of the synthesized compounds. Molecular docking studies were also performed to further understand the binding affinity of these compounds with PDBID 1V9E which confirmed that the synthesized derivatives bind in the active binding site of the target protein. Based upon our results, it is proposed that compound 3b may serve as a lead structure to design more potent carbonic anhydrase inhibitors.
Cobalt Catalysts for Alkene Hydrosilylation under Aerobic Conditions without Dry Solvents or Additives
Authors: Gutiérrez‐Tarriño Silvia , Concepción Patricia , Oña‐Burgos Pascual
Published: October 2018

Alkene hydrosilylation is typically performed with Pt catalysts, but inexpensive base‐metal catalysts would be preferred. Here, we report a simple method for the use of air‐stable cobalt catalysts for anti‐Markovnikov alkene hydrosilylation that can be used under aerobic conditions without dry solvents or additives. These catalysts can be generated from low‐cost commercially available materials. In addition, these catalysts possess good catalytic ability for both hydrosilanes and hydroalkoxysilanes. Finally, a mechanistic study demonstrates that the silane and the catalyst generate a Co–H species in the course of the reaction, which has been observed by in situ Raman spectroscopy.
Synthesis of Heterohelicenes by a Catalytic Multi‐Component Povarov Reaction
Authors: Viglianisi Caterina , Biagioli Chiara , Lippi Martina , Pedicini Maria , Villani Claudio , Franzini Roberta , Menichetti Stefano
Published: October 2018

A multi‐component Povarov reaction was used for the preparation of [4], [5] and [6]aza‐ and azaoxahetero helical‐shaped compounds. The oxidation of the tetrahydroquinolinic primary Povarov adducts to the aromatic quinolines is mandatory to achieve a helical‐shaped structure and can be carried out in a one‐pot fashion with DDQ. Resolution of [5] and [6]heterohelicenes was successfully performed by chiral HPLC.
Highly Dispersive Gold Nanoparticles on Carbon Black for Oxygen and Carbon Dioxide Reduction
Authors: Kim Yeomin , Jo Ara , Ha Yejin , Lee Yongjin , Lee Dongil , Lee Youngmi , Lee Chongmok
Published: October 2018

Highly dispersive Au nanoparticles on carbon black (Au NPs/CB) were synthesized in situ with co‐present two different reducing agents of NaBH4 at various concentrations and citrate at a constant concentration of 3 mM. The average diameters of Au NPs on carbon support were in the range from 5.8 (±2.4) to 2.0 (±0.4) nm, with 50 particles quantified. Electrocatalytic activities of as‐prepared Au NPs/CB were explored for oxygen reduction reaction (ORR) in basic solution with rotating disk electrode (RDE) and rotating ring‐disk electrode (RRDE) voltammetry. In results, the Au NPs/CB synthesized with 0.2 mM NaBH4 (2.0 nm of Au NPs diameter) represented the highest ORR catalytic activity with electron transfer number of 3.9 and mass activity of 0.25 mA cm−2 μg−1as well as a perfect resistance to methanol contamination. Especially, the half‐wave potential of ORR curve which related to the kinetics of oxygen reduction was more positive compared with previously reported Au‐based ORR catalysts. In addition, the Au NPs/CB prepared with 0.2 mM NaBH4 was also examined as a CO2 reduction catalyst in KHCO3 with KCl solution with scanning electrochemical microscopy (SECM). CO2 was reduced to CO selectively without hydrogen evolution at Au NPs/CB substrate electrode, which was directly monitored with an electrochemical CO microsensor as a tip electrode in SECM. In addition, we have identified the products of CO2 reduction through gas chromatography (GC)‐mass spectrometry (MS), flame ionization detector (FID), and thermal conductivity detector (TCD).
Using an Electrochemical Aptasensor to Early Detect Prostate Specific and Free Prostate Specific Antigens Released by Cancer Cells
Authors: Parra João P. R. L. L. , Crulhas Bruno P. , Basso Caroline R. , Delella Flávia K. , Castro Gustavo R. , Pedrosa Valber A.
Published: October 2018

The detection of prostate cancer (PCa) in its early stage is essential to prevent metastasis. Patients who start their treatment earlier have greater chances to be cured; therefore, several research groups have been developing a simple and non‐invasive methodology to detect PCa. The aim of this article is to report a new method to detect prostate specific (PSA) and free prostate‐specific antigens (PSA) released by cancer cells based on the use of an aptasensor. Scanning electron microscopy (SEM), EDS and cyclic voltammetry were the instruments adopted to assess the surface of the biosensor. According to our results, the aptasensor was highly sensitive and recorded linear response 1–100 ng/ml of PSA and fPSA and detection limit 1.1 ng/ml. Studies on interfering compounds such as human serum protein, ascorbic acid, uric acid and mucin type I have shown low correlation to the used aptamer. Thus, this biosensor could be adopted in the near future to early diagnose PCa.
A Li2S‐Based Sacrificial Layer for Stable Operation of Lithium‐Sulfur Batteries
Authors: Ren Y. X. , Zhao T. S. , Liu M. , Jiang H. R. , Xiong C.
Published: October 2018

The polysulfide shuttle effect forms a formidable barrier for lithium‐sulfur (Li−S) battery technology, as it results in serious side reactions on the anode surface and shortens the battery's cyclability. In this work, we propose a facile yet effective preparation of the Li2S‐based sacrificial layer (LSL) as the separator to retard polysulfide crossover. On one hand, before polysulfides (PS) reach the anode surface and react with Li metal, low‐order Li2S prefilled inside the porous separator can chemically interact with PS and sterically physically block PS diffusion. On the other hand, the loss of Li2S in LSL can be replenished by the chemical disproportion of polysulfides, rendering the LSL with excellent endurance over cycling. With the optimized LSL, the Li/polysulfide battery achieves a stabilized discharge capacity at 25 °C (>950 mAh g−1 for 300 cycles, 0.5 C) and demonstrates an excellent thermal stability even at 55 °C (>870 mAh g−1 for 150 cycles, 1 C). The strategy is further generalized to other sulfur based batteries (i. e. Na−S battery), offering new opportunities to improve high‐energy sulfur‐based energy storage technologies.
Mussel‐Inspired Nitrogen‐Doped Porous Carbon as Anode Materials for Sodium‐Ion Batteries
Authors: Sheng Wenbo , Zhang Panpan , Li Wei , Zhang Tao , Tan Deming , Li Yang , Wang Faxing , Zhuang Xiaodong , Feng Xinliang , Jordan Rainer
Published: October 2018

The two feasible approaches such as constructing a porous structure and doping with heteroatoms are used to improve the electrochemical performance of carbon as the anode material for sodium‐ion batteries (SIBs). A facile colloidal crystal templating method to prepare mussel‐inspired nitrogen‐doped porous carbon derived from polydopamine (N‐cPDA) for SIBs with superior electrochemical performance is demonstrated. The N‐cPDA is synthesized by carbonization of polydopamine (PDA) that is polymerized in the presence of self‐assembled poly (methyl methacrylate) particles. The N‐cPDA exhibits a high reversible capacity of 301 mAh g−1 at 0.03 A g−1 and a long cycle lifetime, retaining 80% of the initial capacity after 900 cycles. Furthermore, the first‐principle calculations are performed to evaluate the influences of the N‐doped porous structure on the Na+ diffusion barrier and electronic conductivity, which provides an insight into developing and designing the new anode materials for SIBs.
A point process analysis of cloud‐to‐ground lightning strikes in urban and rural Oklahoma areas
Authors: Hernandez‐Magallanes Irma , Genton Marc G.
Published: October 2018

Lightning is a natural event that can cause severe human and financial losses. This work introduces a probability risk assessment of the occurrence of the cloud‐to‐ground (CG) lightning in urban and rural areas of Oklahoma. CG lightning, although not the most common type, is the most damaging. Previous studies have reported that urban areas experience an increase in the frequency of CG lightning events, during warm months. This increase poses serious threats to urban industries and electronic systems. Lightning strikes are point process in nature, although this quality has not been exploited in previous studies. We utilize a probability model for the spatiotemporal point process of CG lightning to estimate the risk of a CG lightning strike for a particular location and time. The data are discretized into small spatiotemporal cells (voxels), and then, we fit a generalized additive model with a complementary log–log link function using the location and the day of occurrence of the strike as explanatories. On the basis of this model, we compared the urban and rural monthly fitted rates of CG lightning strikes. We found that the rate in the rural area is smaller than the rate in the Tulsa metropolitan area during the warm months; however, it is larger than the rate in the Oklahoma metropolitan area during May and June.
Assessing Policy Process Knowledge: A Systematic Review of Three Theoretical Approaches that are Applied to Cases of Policy Change
Authors: van der Heijden Jeroen , Kuhlmann Johanna
Published: October 2018

This article seeks to understand how knowledge of the policy process, and especially of policy change, is generated. For three dominant approaches—punctuated equilibrium theory, incremental change theorizing, and institutional isomorphism theorizing—we ask where, by whom, and especially how these theoretical approaches have been applied in empirical studies. Answering these questions is relevant for synthesizing knowledge on policy change across such studies. For a stratified sample of 153 empirical articles, we find that the theories have mainly been applied for single‐n or small‐n studies at the national level, in western countries, and by scholars affiliated with western universities. We also find that the theoretical approaches are, generally, only partially and loosely operationalized. This limits the generic lessons we can draw from this body of empirical work.
Determination of the effects of different high‐temperature treatments on texture and aroma characteristics in Alaska pollock surimi
Authors: Zhang Hua , Zhu Yaozhou , Chen Shi , Xu Changhua , Yu Yan , Wang Xichang , Shi Wenzheng
Published: October 2018

This study tested the gel properties, quality of Alaska pollock surimi subjected to different temperature treatments. Results showed that when the heating temperature is 110°C, the water‐holding capacity (WHC) and texture of the surimi and gel strength increased, but as the heating temperature increased, the gel strength decreased significantly (p < 0.05), and ultimately destroyed. The heating temperature had no significant effect on the whiteness of the surimi gel, although it did have a significant effect on volatile components (p < 0.05). Fourier transform infrared (FT‐IR) spectroscopy suggested that with increasing temperature, protein secondary structure of the random coil received maximum damage, leading to protein aggregation and ultimately greatly reduced gel strength. At 100, 105, 110, 115, and 121°C, the surimi gel was determined 37, 46, 49, 52, and 56 volatile components, from of aldehydes, ketones, alcohols, hydrocarbons, and aromatic compounds. These results indicate that heat treatments have an important influence on the gel properties and volatile components of Alaskan pollock surimi gel, and the treatment parameters can be valuable for the production of ready‐to‐use minced fish products.
Ameliorative effect of Ruellia tuberosa L. on hyperglycemia in type 2 diabetes mellitus and glucose uptake in mouse C2C12 myoblasts
Authors: Ko Chih‐Yuan , Lin Ru‐Hai , Zeng Yi‐Ming , Chang Wen‐Chang , Huang Da‐Wei , Wu James Swi‐Bea , Chang Yu‐Fang , Shen Szu‐Chuan
Published: October 2018

Ruellia tuberosa L. (RTL) exhibits a wide range of phytochemical activities, for example, on treatment of diabetes mellitus (DM), in Orient. There is, however, few study regarding the effect of RTL on glycemic‐related homeostasis in type 2 DM (T2DM). We investigated the effect of RTL aqueous and ethanolic extracts on hypoglycemia in high‐fat diet (HFD)‐fed plus streptozotocin (STZ)‐induced T2DM rats, and examined the effect of RTL on glucose uptake in tumor necrosis factor‐α‐induced insulin‐resistant mouse C2C12 myoblasts, a mouse skeletal muscle cell line. The administration of 100 or 400 mg kg BW−1 day−1 of RTL aqueous or ethanolic extracts once a day for 4 weeks significantly ameliorated hyperglycemia, hyperinsulinemia, and the insulin resistance (IR) index in diabetic rats. RTL either aqueous or ethanolic extract at a concentration of 25–800 μg/ml significantly improved glucose uptake in insulin‐resistant mouse C2C12 myoblasts, indicating inhibiting the IR in skeletal muscles. These evidences suggest that RTL ameliorates hyperglycemia in HFD/STZ‐induced T2DM rats may be attributed to the alleviation of IR in skeletal muscles.
Prognostic role of epiregulin/amphiregulin expression in recurrent/metastatic head and neck cancer treated with cetuximab
Authors: Kogashiwa Yasunao , Inoue Hitoshi , Kuba Kiyomi , Araki Ryuichiro , Yasuda Masanori , Nakahira Mitsuhiko , Sugasawa Masashi
Published: October 2018

Background

Cetuximab combined with chemoradiotherapy chemotherapy is the standard therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However, survival benefit is limited. The purpose of this study was to investigate the expression of epiregulin (EREG) and amphiregulin (AREG), as predictive prognostic markers for the efficacy of cetuximab combined with chemotherapy in R/M HNSCC.

Methods

We conducted a retrospective analysis of 37 patients diagnosed with R/M HNSCC. Tumor samples were analyzed for EREG and AREG mRNA gene expression, and clinical outcomes evaluated.

Results

Values of EREG and AREG were associated with significantly longer overall survival (OS) (P = .03 and P = .01, respectively), as well as progression‐free survival (PFS) (P = .04 and P = .04, respectively). Multivariate analysis revealed that AREG expression was significantly associated with OS and PFS.

Conclusions

Patients with recurrent/metastatic HNSCC with higher EREG and AREG gene expression appear to benefit more from cetuximab combined with chemoradiotherapy chemotherapy than those with lower expression.
Male squirting: Analysis of one case using color Doppler ultrasonography
Authors: Hara Ryoei , Nagai Atsushi , Nakatsuka Tohta , Ohira Shin , Fujii Tomohiro , Miyaji Yoshiyuki
Published: October 2018

Introduction

There is no scientific evidence for the mechanism of male squirting, although the term is common in mass media. Here, we describe the first recording of male squirting using color Doppler ultrasonography.

Case presentation

We recruited a 25‐year‐old male volunteer who was able to have male squirting. A transrectal ultrasound probe was inserted into the rectum and male squirting was observed following normal ejaculation. With penis stimulation for a further 20 s after ejaculation, translucent misty fluids with a creatine level similar to that of urine came from the extraurethral orifice for about 60 s. Color Doppler ultrasonography recorded strong contraction of the prostate and pelvic striated muscles just before male squirting, and then the stream went from the urinary bladder through the prostatic urethra.

Conclusion

In male squirting, urine in the bladder gushes out from the external urethral orifice due to strong contraction of the prostate and pelvic striated muscles.
Classification of established atopic dermatitis in children with the in vivo imaging methods
Authors: Lee Jyh‐Hong , Shih Yuan‐Ta , Wei Ming‐Liang , Sun Chi‐Kuang , Chiang Bor‐Luen
Published: October 2018

Atopic dermatitis (AD) is a cutaneous disease resulting from a defective barrier and dysregulated immune response. The severity scoring of atopic dermatitis (SCORAD) is used to classify AD. Noninvasive imaging approaches supplementary to SCORAD were investigated. Cr:forsterite laser‐based microscopy was employed to analyze endogenous third‐harmonic generation (THG) and second‐harmonic generation (SHG) signals from skin. Imaging parameters were compared between different AD severities. Three‐dimensional reconstruction of imaged skin layers was performed. Finally, statistic models from quantitative imaging parameters were developed for predicting disease severity. Our data demonstrate that THG signal intensity of lesional skin in AD were significantly increased and was positively correlated with AD severity. Characteristic gray level co‐occurrence matrix (GLCM) values were observed in more severe AD. In the 3D reconstruction video, individual dermal papilla and obvious fibrosis in the upper papillary dermis were easily identified. Our estimation models could predict the disease severity of AD patients with an accuracy of nearly 85%. The THG signal intensity and characteristic GLCM patterns are associated with AD severity and can serve as quantitative predictive parameters. Our imaging approach can be used to identify the histopathological changes of AD objectively, and to complement the SCORAD index, thus improving the accuracy of classifying AD severity.
MiR‐143‐3p suppresses cell proliferation, migration, and invasion by targeting Melanoma‐Associated Antigen A9 in laryngeal squamous cell carcinoma
Authors: Han Liang , Tang Mingming , Xu Xinjiang , Jiang Bin , Wei Yingze , Qian Hongyan , Lu Xueguan
Published: October 2018

Previously we found that melanoma‐associated antigen‐A9 (MAGE‐A9) was a significantly upregulated biomarker in laryngeal squamous cell carcinoma (LSCC). A high expression of MAGE‐A9 indicates an unfavorable survival outcome, and the MAGE‐A9 expression level is an independent prognostic factor of LSCC. To explore the mechanism of MAGE‐A9 upregulation, several predicted regulatory microRNAs were screened and validated in LSCC cells. In the current study, we found that miR‐143‐3p (MAGE‐A9 related miRNAs) expression levels correlated negatively with the MAGE‐A9 protein expression in LSCC tissues. Dual‐luciferase reporter assays and Western blot analysis revealed MAGE‐A9 to be a direct target of miR‐143‐3p. Furthermore, a series of in vitro gain‐ and loss‐of‐function assays revealed that miR‐143‐3p inhibited LSCC cell proliferation, migration, and invasion. Also, miR‐143‐3p suppressed LSCC tumorigenesis in vivo. These effects were clinically relevant, as a lower expression of miR‐143‐3p occurred in severer clinical stages and represented poor overall survival in patients with LSCC. Taken together, these results suggest that downregulation of miR‐143‐3p contributes to tumor progression through upregulation of MAGE‐A9. The expression level of these two key molecules maintained LSCC progression, thus, highlighting the potential of miR‐143‐3p as a therapeutic target for human LSCC.
Computational insights into pH‐dependence of structure and dynamics of pyrazinamidase: A comparison of wild type and mutants
Authors: Esmaeeli Reza , Mehrnejad Faramarz , Mir‐Derikvand Mohammad , Gopalpoor Niloofar
Published: October 2018

The mycobacterial enzyme pyrazinamidase (PZase) is the target of key tuberculosis drug, pyrazinamide. Mutations in PZase cause drug resistance. Herein, three point mutations, W68G, L85P, and V155G, were investigated through over 8 µs of molecular dynamics simulations coupled with essential dynamics and binding pocket analysis at neutral (pH = 7) and acidic (pH = 4) ambient conditions. The 51‐71 flap region exhibited drastic displacement leading to enlargement of binding cavity, especially at the lower pH. Accessibility of solvent to the active site of the mutant enzymes was also reduced. The protonation of key surface residues at low pH results in more contribution of these residues to structural stability and integrity of the enzyme and reduced interactions with solvent molecules, which acts as a cage, keeping the enzyme together. The observed results suggest a pattern of structural alterations due to point mutations in PZase, which is consistent with other experimental and theoretical investigations and, can be harnessed for drug design purposes.
Angiotensin‐converting enzyme insertion/deletion (rs106180) and angiotensin type 1 receptor A1166C (rs106165) genotypes and psoriasis: Correlation with cellular immunity, lipid profile, and oxidative stress markers
Authors: Tanhapour Maryam , Falahi Badieh , Vaisi‐Raygani Asad , Bahrehmand Fariborz , Kiani Amir , Rahimi Zohreh , Vaisi‐Raygani Ali‐Akbar , Shakiba Ebrahim , Pourmotabbed Tayebeh
Published: October 2018

Psoriasis is a chronic inflammatory skin condition and angiotensin‐converting enzyme (ACE) is a key circulating enzyme converting angiotensin (Ang) I to the vasoactive peptide Ang II. The exact role of ACE insertion (I)/deletion (D) polymorphism (rs106180) in psoriasis is not clear. We aimed to examine whether the ACE I/D and Ang II type 1 receptor (AT1R) A1166C‐polymorphisms (rs106165), lipid profile, and stress oxidative are associated with susceptibility to psoriasis. One hundred patients with psoriasis and 100 sex‐ and age‐matched unrelated healthy controls were recruited for this case‐control study. ACE I/D and AT1R A1166C polymorphisms were identified by the polymerase chain reaction (PCR) and PCR‐restriction fragment length polymorphism, respectively, malondialdehyde (MDA) was detected by the high‐performance liquid chromatography, serum arylesterase (ARE) activity of paraoxonase and catalase activities were detected by the spectrophotometry, superoxide dismutase (SOD) activity and vascular adhesion protein (VAP)‐1 were measured by ELISA. The presence of C allele of AT1R A1166C and I allele of ACE considerably increased the risk of psoriasis by 6.42‐fold (P < 0.001). The distribution of II‐genotype of ACE was significantly higher in psoriasis patients than in control group and increased the risk of disease by 3.11‐times (P = 0.023). The higher levels of MDA in patients and the higher activity of SOD, ARE, and CAT was observed in healthy controls with I/D+I/I‐genotype of ACE I/D. This study for the first time demonstrated that the ACE I/D and AT1R A 1166C genes polymorphisms robustly increases the risk of developing psoriasis in population from west of Iran. In addition, these individuals had significantly higher VAP‐1 and MDA concentration and lower enzymatic and nonenzymatic antioxidant‐status, suggesting that psoriatic patients carrying C allele of AT1R1166 polymorphism may be more susceptible to cardiovascular disease and myocardial infarction compared with A allele.
TrkC‐miR2 regulates TGFβ signaling pathway through targeting of SMAD3 transcript
Authors: Dokanehiifard Sadat , Soltani Bahram M.
Published: October 2018

TrkC,neurotrophin receptor, functions inside and outside of the nervous system and has a crucial effect on the regulation of cardiovascular formation. Recently, we introducedTrkC‐miR2as a novel microRNA located inTrkCgene, which is a regulator of the Wnt signaling pathway. Here, we presented a lot of evidence showing thatTrkC‐miR2also regulates the transforming growth factor‐beta (TGFβ) signaling pathway. Bioinformatics studies predictedSMAD3as one of the bona fideTrkC‐miR2target genes. Quantitative reverse transcription PCR (RT‐qPCR), Western blot analysis, and dual luciferase assay analysis confirmed thatSMAD3is targeted byTrkC‐miR2. On the other hand, overexpression ofTrkC‐miR2in cardiosphere‐derived cells (CDCs) rendered downregulation ofTGFβR1,TGFβR2, andSMAD7detected by RT‐qPCR. Consistently, an inverse correlation of expression betweenTrkC‐miR2andSMAD3genes was detected during the course of CDC differentiation, and also during the course of human embryonic stem cells differentiation to cardiomyocytes. Overall, we conclude thatTrkC‐miR2downregulates the expression ofSMAD3and potentially regulates the TGFβ signaling pathway. Knowing its approved effect on Wnt signaling,TrkC‐miR2here is introduced as a common regulator of both the Wnt and TGFβ signaling pathways. Therefore, it may be a potential key element in controlling both of these signaling pathways in cell processes like colorectal cancer and cardiogenesis.
Upregulation of lincRNA‐p21 in thoracic aortic aneurysms is involved in the regulation of proliferation and apoptosis of vascular smooth muscle cells by activating TGF‐β1 signaling pathway
Authors: Hu Wenxian , Wang Zhaowei , Li Qiang , Wang Jinjun , Li Lin , Jiang Guixi
Published: October 2018

Objective

Long intergenic noncoding RNA‐p21 (lincRNA‐p21) has been proved in the pathogenesis of aortic aneurysms, while its functionality in thoracic aortic aneurysms (TAA) and the mechanism of function remains unclear. Therefore our study aimed to investigate the role of lincRNA‐p21 in TAA.

Methods

Aortic media specimens and blood samples were collected from both patients with TAA and healthy controls. Expression of lincRNA‐p21 in those tissues was detected by reverse‐transcription quantitative polymerase chain reaction (qRT‐PCR). Diagnostic values of lincRNA‐p21 in aortic media and blood for TAA were evaluated by receiver operating characteristic curve analysis. LincRNA‐p21 overexpression human vascular smooth muscle cells (VSMCs) were prepared and the effects of lincRNA‐p21 overexpression on cell proliferation and apoptosis were explored by cell counting kit‐8 assay and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay, respectively. Expression of lincRNA‐p21 and transforming growth factor β1 (TGF‐β1) in VSMCs with different treatment was detected by qRT‐PCR and Western blot analysis, respectively.

Results

Expression of lincRNA‐p21 in aortic media tissues and blood was significantly upregulated in TAA patients than in healthy controls. Expression of lincRNA‐p21 in aortic media and blood can be used to effectively distinguish TAA patients form healthy controls. LincRNA‐p21 overexpression inhibited proliferation and promoted apoptosis of VSMCs, while TGF‐β1 inhibitor reduced those effects. LincRNA‐p21 overexpression upregulated TGF‐β1 expression, while TGF‐β1 activator showed no significant effects on lincRNA‐p21 expression in VSMC.

Conclusion

LincRNA‐p21 participates in TAA by regulating the proliferation and apoptosis of VSMCs through the activation of TGF‐β1 signaling pathway.
Comparing the efficacy of pain managements after total hip arthroplasty: A network meta‐analysis
Authors: Liu Pengcheng , Wu Yingbo , Liang Zhiquan , Deng Yingjie , Meng Qingcai
Published: October 2018

The aim of our current study is to compare efficiency of various interventions implemented for pain management after total hip arthroplasty (THA). PubMed and EMBASE were searched for randomized clinical trials (RCTs) reporting the pain scales for evaluate the efficacy of pain control after THA including at least one pair of direct control groups. Pain scale values and the associated 95% credible interval (CrI) were used to describe efficacy. Surface under the cumulative ranking curve (SUCRA) of each means of pain control was calculated to compare the relative ranking of different interventions. Thirty‐five eligible literatures were involved in data analysis. The interventions for postoperative pain management we examined were psoas compartment block (PCB), posterior nerve block (PNB), fascia iliaca block (FIB), periarticular injection (PAI), femoral nerve block (FNB), lumbar plexus block (LPB), spinal anesthesia (SA), epidural analgesia (EPI), intrathecal morphine (IA), intravenous patient‐controlled analgesia (IV‐PCA), patient‐controlled analgesia (PCA), onsteroidal anti‐inflammatory drug (NSAID), local infiltration analgaesia (LIA), and reverse LIA (rLIA). In 0 to 6 hours analysis, patients under SA were found to have significantly lower pain score and SA was ranked the best. In 6 to 12 hours analysis, SA was found to be significantly more effective than other interventions and its SUCRA was the highest. No intervention showed a significant effect on reducing pain score for 12 to 24 hours and 24 to 48 hours after THA. SA is the best intervention to reduce THA postoperative pain in the first 24 hours. LPB is a better choice to reduce pain 12 to 48 hours after THA.
Identification of differentially expressed long noncoding RNAs in human knee osteoarthritis
Authors: Xiao Ke , Yang Yuemei , Bian Yanyan , Feng Bin , Li Zeng , Wu Zhihong , Qiu Guixing , Weng Xisheng
Published: October 2018

Long noncoding RNAs (lncRNAs) are considered a novel class of regulatory factors in many diseases, but their biological function and the signaling pathway involved in osteoarthritic (OA) remain unknown. To identify the lncRNAs specifically expressed in OA cartilage, the expression of lncRNAs in OA cartilage was measured using an illumina sequencing platform. Furthermore, differentially expressed transcripts of uncertain coding potential (TUCPs) and messenger RNAs (mRNAs) were identified. The colocated target genes and the possible role of lncRNAs as a competing endogenous RNA (ceRNA) were predicted. Based on 19 samples from osteoarthritis patients of knees, 580 significantly dysregulated lncRNAs as well as differently expressed TUCPs and mRNAs were identified. Four differently expressed lncRNAs (SNHG5, ZFAS1, GAS5, and DANCR) involved in OA cartilage were analyzed by protein‐protein interactions network and ceRNA regulatory network. Part of our results were consistent with previous studies, and 96 novel differently expressed lncRNAs were identified in OA. These results could expand our knowledge of the OA mechanism.
Embryonic poly(A)‐binding protein is differently expressed and interacts with the messenger RNAs in the mouse oocytes and early embryos
Authors: Uysal Fatma , Ozturk Saffet
Published: October 2018

The embryonic poly(A)‐binding protein (EPAB) functions in the translational regulation of the maternal messenger RNAs (mRNAs) required during oocyte maturation, fertilization, and early embryo development. Since there is no antibody specific to mammalian EPAB protein, all studies related to the Epab gene could be performed at the mRNA levels except for the investigations in the
Xenopus. In this study, we have produced an EPAB‐specific antibody. When we examined its expressional distribution in the mouse gonadal and somatic tissues, the EPAB protein was found to be expressed only in the mouse ovary and testis tissues, but it is undetectable level in the somatic tissues including stomach, liver, heart, small intestine, and kidney. Additionally, the spatial and temporal expression patterns of the EPAB and poly(A)‐binding protein cytoplasmic 1 (PABPC1) proteins were analyzed in the mouse germinal vesicle (GV) and metaphase II (MII) oocytes, one‐cell, and two‐cell embryos. While EPAB expression gradually decreased from GV oocytes to two‐cell embryos, the PABPC1 protein level progressively increased from GV oocytes to one‐cell embryos and remarkably declined in the two‐cell embryos (
P < 0.05). We have also described herein that the EPAB protein interacted with
Epab,
Pabpc1,
Ccnb1,
Gdf9, and
Bmp15 mRNAs dependent upon the developmental stages of the mouse oocytes and early embryos. As a result, we have first produced an EPAB‐specific antibody and characterized its expression patterns and interacting mRNAs in the mouse oocytes and early embryos. The findings suggest that EPAB in cooperation with PABPC1 implicate in the translational control of maternal mRNAs during oogenesis and early embryo development.
Photodynamic treatment with anionic nanoclays containing curcumin on human triple‐negative breast cancer cells: Cellular and biochemical studies
Authors: Khorsandi Khatereh , Hosseinzadeh Reza , Shahidi Fedora Khatibi
Published: October 2018

Photodynamic treatment is a minimally invasive and clinically approved procedure for eliminating selected malignant cells with activation of a photosensitizer agent at a specific light. Little is known, however, about the phototoxic properties of curcumin, as a natural phenolic compound, against different types of cancers. It is generally accepted that cellular damage occurs during photo treatment. There is a limitation in using of curcumin as a drug due to its low solubility, but nanoparticles such as anionic nanoclays or layered double hydroxide (LDH) could overcome it. The aim of this study was to investigate cellular responses to curcumin‐LDH nanoparticles after photodynamic treatment of MDA‐MB‐231 human breast cancer cells. For this purpose, the MDA‐MB‐231 human breast cancer cell line treated with curcumin‐LDH nanoparticle and then irradiated (photodynamic treatment). After irradiation, lactate dehydrogenase assay, clonogenic cell survival, cell death mechanisms such as autophagy and apoptosis were determined. Cell cycle distribution after photodynamic therapy (PDT) and also intracellular reactive oxygen species (ROS) generation were measured. The result showed that curcumin‐LDH–PDT has a cytotoxic and antiprolifrative effect on MDA‐MB‐231 human breast cancer cells. Curcumin‐LDH–PDT induced autophagy, apoptosis, and G0/G1 cell cycle arrest in human breast cancer cell line. Intracellular ROS increased in MDA‐MB‐231 cancer cell line after treatment with curcumin‐LDH along with irradiation. The results suggest that curcumin‐LDH nanoparticle could be considered as a novel approach in the photodynamic treatment of breast cancer.
miR‐17‐5p promotes proliferation and epithelial‐mesenchymal transition in human osteosarcoma cells by targeting SRC kinase signaling inhibitor 1
Authors: Zhao Xuefeng , Xu Yan , Sun Xiaoya , Ma Yuan , Zhang Yan , Wang Yadong , Guan Hongya , Jia Zhen , Li Yuebai , Wang Yisheng
Published: October 2018

MicroRNA‐17‐5p (miR‐17‐5p) and epithelial‐mesenchymal transition (EMT) have been reported to participate in the development and progression of multiple cancers. However, the relationship between the miR‐17‐5p and EMT in osteosarcoma (OS) is still poorly understood. This study was to investigate the effects of the miR‐17‐5p and its potential mechanism in regulating proliferation, apoptosis, and EMT of human OS. Quantitative real‐time PCR was used to detect the miR‐17‐5p and SRC kinase signaling inhibitor 1 (SRCIN1) messenger RNA expression in OS specimens and cell lines. After transfection with miR‐17‐5p inhibitors, proliferation, apoptosis, migration, and invasion of OS cells were assessed by using the Cell Counting Kit‐8, the annexin V‐FITC apoptosis, wound‐healing, and transwell assays. The SRCIN1 was validated as a target of the miR‐17‐5p through bioinformatics algorithms and luciferase reporter assay. Moreover, the expression of EMT markers, E‐cadherin, N‐cadherin, and Snail was identified by the Western blot analysis. MiR‐17‐5p was significantly upregulated in OS tumor samples and cell lines. It inhibited proliferation and EMT, and promoted apoptosis in OS. The SRCIN1 was identified as a direct target of the miR‐17‐5p. Silenced miR‐17‐5p could change the expression of EMT markers, such as upregulating the expression of E‐cadherin, and downregulating the expression of N‐cadherin and Snail through targeting the antioncogenic SRCIN1. These findings suggest that the miR‐17‐5p promotes cell proliferation, and EMT in human OS by directly targeting the SRCIN1, and reveal a branch of the miR‐17‐5p/SRCIN1/EMT signaling pathway involved in the progression of OS.
A novel agent attenuates cardiotoxicity and improves antitumor activity of doxorubicin in breast cancer cells
Authors: Zhang Ying , Deng Hongkuan , Zhou Hefeng , Lu Yucong , Shan Luchen , Lee Simon Ming‐Yuen , Cui Guozhen
Published: October 2018

Doxorubicin (Dox) is a well‐known chemotherapeutic agent used in the treatment of various cancers. However, Dox‐induced cardiotoxicity limits its further clinical use. We have previously reported a small molecular named biotin‐conjugated ADTM analog (BAA) that exhibits cytoprotective effects against oxidative stress–induced cell injury in cardiomyoblast H9c2 cells. Here, the protective effects of BAA, indexed by attenuation of the cardiotoxicity induced by Dox as well as synergistic antitumor activity that increases the chemotherapeutic efficacy of Dox were investigated. Our results demonstrated that BAA significantly ameliorated Dox‐induced toxicity in the H9c2 cells and zebrafish models. In addition, BAA attenuated Dox‐induced endoplasmic reticulum (ER) stress in H9c2 cells. An ER stress inhibitor, 4‐phenylbutyric acid, reversed the protective effect of BAA in H9c2 cells. In contrast, in human breast tumor MDA‐MB‐231 cells, BAA significantly enhanced Dox‐induced cytotoxicity through upregulating Dox‐induced ER stress response. Taken together, our findings indicate that Dox combined with BAA can significantly enhance its antitumor activity in breast cancer cells and reduce its cardiotoxicity, at least in part, by mediating ER stress activation.
Retracted: Role of RKIP in human hepatic stellate cell proliferation, invasion, and metastasis
Authors: Huang Quanfang , Wei Jinbin , Wei Ling , Zhang Xiaolin , Bai Facheng , Wen Shujuan , Wei Yuanyuan , Tan Shimei , Lu Zhongpeng , Lin Xing
Published: October 2018

The purpose of this study was to investigate the effect of Raf kinase inhibitor protein (RKIP) on the growth, apoptosis, invasion, and metastasis of human hepatic stellate cell line (LX‐2). A recombinant plasmid (pcDNA3.1‐RKIP) or RKIP‐targeting small interfering RNA (siRNA) vector (siRNA‐RKIP) was transfected into LX‐2 cells to interfere with the RKIP expression. The results demonstrated that increased RKIP expression significantly reduced cell viability, clonogenic growth, and invasion. Further, it promoted cell apoptosis and induced cell cycle arrest in the G1 phase. Overexpression of RKIP led to inactivation of LX‐2 cells, as evidenced by the decrease in the expression levels of collagen I and α‐smooth muscle actin (α‐SMA). In addition, increased RKIP expression significantly reduced the phosphorylation of Raf/extracellular signal‐regulated kinase (ERK)/mitogen‐activated protein kinase (MAPK), the transcriptional activity of nuclear factor‐κB (NF‐κB), and the levels of matrix metalloproteinases‐1 and ‐2. In conclusion, these findings clearly demonstrate that RKIP inhibits LX‐2 cell growth, metastasis, and activation, primarily by downregulating the ERK/MAPK and NF‐κB signaling pathways.