bluuebunny/crossref_metadata_2025 huggingface dataset:
Abamectin induces apoptosis and autophagy by inhibiting reactive oxygen species‐mediated PI3K/AKT signaling in MGC803 cells
Authors: Zhu Shanshan , Zhou Jing , Zhou Zhonglou , Zhu Qiqi
Published: April 2019

Abamectin (ABA) is one of the most widely used compounds in agriculture and veterinary medicine. However, the cytotoxicity of ABA in human gastric cells is utterly unknown. In this study, ABA suppressed the proliferation of MGC803 cells by arresting the cell cycle at the G0/G1‐phase. Moreover, ABA induced mitochondrial‐mediated apoptosis by inducing the loss of mitochondrial membrane potential, upregulation of Bax/Bcl‐2, and activation of caspase‐3. ABA significantly improved the LC3‐II/LC3‐I ratio and reduced P62 protein expression in a dose‐dependent manner. Through detection of the reactive oxygen species (ROS) levels, we found ABA induced the accumulation of intracellular ROS and then reduced PI3K/AKT signaling activation related to MGC803 cell apoptosis and autophagy. Our results indicate that ABA exerts cytotoxic effects on human MGC803 cells through apoptosis and autophagy by inhibiting ROS‐mediated PI3K/AKT signaling. Furthermore, ABA may be a potential risk to human gastric health.
Downregulation of sirtuin 3 by palmitic acid increases the oxidative stress, impairment of mitochondrial function, and apoptosis in liver cells
Authors: Sharma Garima , Parihar Arti , Parihar Priyanka , Parihar Mordhwaj Singh
Published: April 2019

Elevated levels of saturated fatty acids show a strong cytotoxic effect in liver cells. Sirtuin 3 (SIRT3), a mitochondrially localized member of NAD+‐dependent deacetylase has been shown to protect hepatocytes against the oxidative stress. The role of SIRT3 on the cytotoxicity caused by fatty acids in liver cells is not fully understood. The aim of this study was to evaluate the expression level of SIRT3, oxidative stress, and mitochondrial impairments in human hepatoma HepG2 cells exposed to palmitic acid (PA). Our results showed that PA treatment caused the deposition of lipid droplets and resulted in an increased expression of tumor necrosis factor‐α in a dose‐dependent manner. Excessive accumulation of PA induces the reactive oxygen species formation and apoptosis while dissipating the mitochondrial transmembrane potential. The level of SIRT3 expression in both nuclear and mitochondrial fractions in HepG2 cells was decreased with the increase in PA concentrations. However, in the cytosolic fraction, the SIRT3 was undetectable. In conclusion, our results showed that PA caused an increase in inflammation and oxidative stress in HepG2 cells. The exposure of PA also resulted in the decline in transmembrane potential and an increase in apoptosis. The underexpression of nuclear and mitochondrial SIRT3 by PA suggests that the PA target the process that regulates the stress‐related gene expression and mitochondrial functions.
Losartan delays the progression of streptozotocin‐induced diabetic cataracts in albino rats
Authors: Shree Jaya , Choudhary Rajesh , Bodakhe Surendra H
Published: April 2019

The ocular renin‐angiotensin system has become an interesting target for ocular diseases because it has been implicated in various ocular diseases such as diabetic retinopathy, glaucoma, age‐related macular degeneration, uveitis, and hypertensive cataracts. In the present study, we explored the effect of topically and orally administered losartan (an angiotensin receptor blocker) on streptozotocin‐induced diabetic cataract in albino rats. Topical treatment with losartan modulated neither the blood glucose level nor the polyol content but oral treatment with losartan decreased both. Topical and oral treatment with losartan significantly increased the antioxidants (glutathione, glutathione peroxidase, superoxide dismutase, and catalase), decreased the lipid peroxidant malondialdehyde, and restored soluble protein, and insoluble protein and various ions (Na+, K+, and Ca2+) in the lens; however, topical treatment had a better effect than oral treatment. These findings demonstrate that topical administration of losartan significantly reduces the risk of cataract formation without affecting either the blood glucose level or polyol contents.
Microbial contributions to bronchial asthma occurrence in children: A metagenomic study
Authors: Tian Man , Chen Meng , Bao Yuling , Xu Changdi , Qin Qiaozhi , Zhang Wenxin , He Yuting , Shao Qi
Published: April 2019

Bronchial asthma, a common chronic respiratory disease in children, is traditionally regarded as a noninfectious disease. Current hypotheses, however, argue that asthma can be caused by microbial infection. We, therefore, hypothesize that a variety of microbes are more commonly found in the sputum of children with asthma, and these microbes may contribute to the occurrence and development of asthma. The present study proposes to use metagenomic approach to explore microbial diversity and to identify the microbial community characteristics of sputum from children with asthma. We found that microbial communities in the sputum of children differed significantly between asthmatics and controls. Kruskal‐Wallis testing showed that 16 phyla, 104 genera, and 159 species were significantly downregulated, whereas two phyla including Platyhelminthes phylum and Chordata phylum, two genera including Spirometra genus and Homo sapiens, and the Spirometra erinaceieuropaei species were significantly upregulated in asthma patients compared with controls (P < 0.05). Among them, H. sapiens and S. erinaceieuropaei exhibited 2.3‐ and 2.0‐fold overabundance in asthmatics vs controls, respectively. Meanwhile, metastats assay demonstrated that 31 phyla, 400 genera, and 813 species were significantly downregulated, whereas two phyla, 10 genera, and 16 species were significantly upregulated in asthma patients compared with controls (P < 0.05). Among them, Tetrahymena thermophila and Candidatus Zinderia insecticola exhibited 4.7‐fold overabundance in asthmatics vs controls. Our study establishes a link between microbial infection and the mechanisms leading to asthma development, which will be useful for developing novel diagnostic biomarkers and aiding in the prevention and control of asthma.
Effects of quercetin on microRNAs: A mechanistic review
Authors: Akbari Kordkheyli Vahid , Khonakdar Tarsi Abbas , Mishan Mohammad A. , Tafazoli Alireza , Bardania Hassan , Zarpou Setareh , Bagheri Abouzar
Published: April 2019

MicroRNA (miRNA)‐dependent pathways are one of the newest gene regulation mechanisms in various diseases, particularly in cancers. miRNAs are endogenous noncoding RNAs with about 18 to 25 nucleotide length, which can regulate the expression of at least 60% of human total genome posttranscriptionally. Quercetin is the most abundant flavonoid in a variety of fruits, flowers, and medical herbs, known as a strong free radical scavenger that could show antioxidant, anti‐inflammatory, and antitumor activities. Recent studies also reported its strong impact on various miRNA expressions in different abnormalities. In this review, we aimed to summarize the studies focused on the effects of quercetin on different miRNA expressions to more clear the main possible mechanisms of quercetin influences and introduce it as a beneficial agent for regulation of miRNAs in various biological directions.
Identification of consensus sequence from matrix attachment regions and functional analysis of its activity in stably transfected Chinese hamster ovary cells
Authors: Gao Jian‐Hui , Wang Tian‐Yun , Zhang Mao‐Ying , Shi Fang , Gu Shan‐Zhi
Published: April 2019

Matrix attachment regions (MARs) can enhance transgene expression levels and maintain stability. However, the consensus sequence from MARs and its functional analysis remains to be examined. Here, we assessed a possible consensus sequence from MARs and assessed its activity in stably transfected Chinese hamster ovary (CHO) cells. First, we analyzed the effects of 10 MARs on transfected CHO cells and then analyzed the consensus motifs from these MARs using a bioinformatics method. The consensus sequence was synthesized and cloned upstream or downstream of the eukaryotic vector. The constructs were transfected into CHO cells and the expression levels and stability of enhanced green fluorescent protein were detected by flow cytometry. The results indicated that eight of the ten MARs increased transgene expression in transfected CHO cells. Three consensus motifs were found after bioinformatics analyses. The consensus sequence tandemly enhanced transgene expression when it was inserted into the eukaryotic expression vector; the effect of the addition upstream was stronger than that downstream. Thus, we found a MAR consensus sequence that may regulate the MAR‐mediated increase in transgene expression.
Implementation of a fast method for the measurement of carnitine palmitoyltransferase 2 activity in lymphocytes by tandem mass spectrometry as confirmation for newborn screening
Authors: Tucci Sara , Behringer Sidney , Sturm Marga , Grünert Sarah C. , Spiekerkoetter Ute
Published: April 2019

Carnitine palmitoyltransferase II (CPT2) is a rare autosomal recessive inherited disorder affecting mitochondrial β‐oxidation. Confirmation diagnostics are mostly based on molecular sequencing of the CPT2 gene, especially to distinguish CPT2 and carnitine:aclycarnitine translocase deficiencies, which present with identical acylcarnitine profiles on newborn screening (NBS). In the past, different enzyme tests in muscle biopsies have been developed in order to study the functional effect in one of the main target organs. In this study, we implemented a method for measurement of CPT2 enzyme activity in human lymphocytes with detection of the reaction products via liquid chromatography mass spectrometry to enable the simultaneous evaluation of the functional impairment and the clear diagnosis of the disease. CPT2 activity was measured in samples collected from CPT2 patients (n = 11), heterozygous carriers (n = 6), and healthy individuals (n = 52). Seven patients out of 11 were homozygous for the common mutation c.338T>C and showed a residual activity with median values of 19.2 ± 3.7% of healthy controls. Heterozygous carriers showed a residual activity in the range of 42% to 75%. Four individuals carrying the heterozygous mutation c.338T>C showed a 2‐fold higher residual activity as compared to homozygous individuals. Our optimized method for the measurement of CPT2 activity is able to clearly discriminate between patients and healthy individuals and offers the possibility to determine CPT2 activity in human lymphocytes avoiding the need of an invasive muscle biopsy. This method can be successfully used for confirmation diagnosis in case of positive NBS and would markedly reduce the time to define diagnosis.
Head‐to‐head comparison between multiparametric MRI, the partin tables, memorial sloan kettering cancer center nomogram, and CAPRA score in predicting extraprostatic cancer in patients undergoing radical prostatectomy
Authors: Zanelli Elisa , Giannarini Gianluca , Cereser Lorenzo , Zuiani Chiara , Como Giuseppe , Pizzolitto Stefano , Crestani Alessandro , Valotto Claudio , Ficarra Vincenzo , Girometti Rossano
Published: April 2019

Background

It is unclear whether clinical models including the Partin tables (PT), the Memorial Sloan Kettering Cancer Center nomogram (MSKCCn), and the cancer of the prostate risk assessment (CAPRA) can benefit from incorporating multiparametric magnetic resonance imaging (mpMRI) when staging prostate cancer (PCa).

Purpose

To compare the accuracy of clinical models, mpMRI, and mpMRI plus clinical models in predicting stage ≥pT3 of PCa.

Study Type

Prospective monocentric cohort study.

Population

Seventy‐three patients who underwent radical prostatectomy between 2016–2018.

Field Strength/Sequence

3.0T using turbo spin echo (TSE) imaging, single‐shot echoplanar diffusion‐weighted imaging, and T1‐weighted high‐resolution‐isotropic‐volume‐examination (THRIVE) contrast‐enhanced imaging.

Assessment

We calculated the probability of extraprostatic extension (EPE) using the PT and MSKCC, as well as the CAPRA score. Three readers with 2–8 years of experience in mpMRI independently staged PCa on imaging.

Statistical Tests

Receiver operating characteristics analysis and logistic regression analysis to investigate the per‐patient accuracy of mpMRI vs. clinical models vs. mpMRI plus clinical models in predicting stage ≥pT3. The alpha level was 0.05.

Results

Median probability for EPE and MSKCCn was 27.3% and 47.0%, respectively. Median CAPRA score was 3. Stage ≥pT3 occurred in 32.9% of patients. Areas under the curve (AUCs) were 0.62 for PT, 0.62 for MSKCCn, 0.64 for CAPRA, and 0.73–0.75 for mpMRI (readers 1–3) (P > 0.05 for all comparisons). Compared with mpMRI, the combination of mpMRI with PT or MSKCCn provided lower AUCs (P > 0.05 for all the readers), while the combination with CAPRA provided significantly higher (P < 0.05) AUCs in the case of readers 1 and 3. On multivariable analysis, mpMRI by reader 1 was the only independent predictor of stage ≥pT3 (odds ratio 7.40).

Data Conclusion

mpMRI was more accurate than clinical models and mpMRI plus clinical models in predicting stage ≥pT3, except for the combination of mpMRI and CAPRA in two out of three readers.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:1604–1613.
Does supply chain visibility affect operating performance? Evidence from conflict minerals disclosures
Authors: Swift Caroline , Guide V. Daniel R. , Muthulingam Suresh
Published: April 2019

Firms are increasingly held accountable for their suppliers' transgressions. Consequently, firms need to develop upstream visibility to exercise control over their supply chains. An emerging body of work has recognized the importance of supply chain visibility and has examined it using analytical models, behavioral methods, and case studies. Still, large‐sample empirical evidence on the benefits of supply chain visibility remains elusive. We seek to bridge this gap by examining conflict minerals disclosures (mandated by the 2010 Dodd‐Frank Wall Street Reform and Consumer Protection Act) and financial reports to evaluate whether firms with greater visibility into their conflict minerals supply chains achieve improved operating and market performance. We use the data from conflict minerals disclosures (Form SD) to distinguish between firms that have high or low visibility into their conflict minerals sources. Then, we use event study methods to analyze differences in operating and market performance between firms with high visibility and firms with low visibility. We find that firms with high visibility into their conflict minerals supply chains achieve higher profitability than comparable firms with less visibility. In addition, we find that firms with high visibility into their conflict minerals supply chains realize improved sales performance and stock market valuations. Our results are relevant to managers because they show that firms can attain operational and market benefits by improving visibility in their supply chains.
Improved antitumor activity of cisplatin combined with Ganoderma lucidum polysaccharides in U14 cervical carcinoma‐bearing mice
Authors: Zhu Jun , Xu Jia , Jiang Ling‐Ling , Huang Jin‐Qun , Yan Jin‐Yu , Chen Yi‐Wan , Yang Qian
Published: April 2019

Research on anticervical cancer is urgently required to enhance clinical outcomes. As a main anticancer drug for cervical carcinoma, cisplatin (CIS) has been used for a lot of years in clinical therapy. However, serious adverse effects including nephrotoxicity and neurotoxicity limit its long‐term treatment. Our main goal of this study is to investigate the improvement of Ganoderma lucidum polysaccharides (GPS) on CIS‐induced antitumor effect of in U14 cervical carcinoma‐bearing mice. The results showed that GPS + CIS could not only inhibit the growth of the tumor but also improve the spleen and thymus indexes. Moreover, little toxicological effects were observed on hepatic function and renal function in GPS + CIS treated mice bearing U14 tumor cells. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly, the expression of Bax increased and the expression of Bcl‐2 decreased dramatically in cervical cancer sections after oral administration of GPS + CIS for 14 days. This GPS/CIS combined therapy represents intriguing therapeutic strategy for U14 cervical carcinoma providing not only superior efficacy but also a higher safety level.
A Spin‐Encoded All‐Dielectric Metahologram for Visible Light
Authors: Ansari Muhammad Afnan , Kim Inki , Lee Dasol , Waseem Muhammad Hamza , Zubair Muhammad , Mahmood Nasir , Badloe Trevon , Yerci Selcuk , Tauqeer Tauseef , Mehmood Muhammad Qasim , Rho Junsuk
Published: April 2019

Dielectric materials that are low‐loss in the visible spectrum provide a promising platform to realize the pragmatic features of metasurfaces. Here, all‐dielectric, highly efficient, spin‐encoded transmission‐type metaholograms (in the visible domain) are demonstrated by utilizing hydrogenated amorphous silicon (a‐Si:H). In comparison to previously reported visible metaholograms based on TiO2 and other dielectric materials, all‐dielectric metasurfaces provide a cost‐effective more straightforwardly fabricated (aspect ratio 4.7), CMOS compatible, and comparably efficient solution in the visible domain. A unique way of utilizing polarization as an extra degree of freedom in the design to implement transmission‐type helicity‐encoded metaholograms is also proposed. The produced images exhibit high fidelity under both right and left circularly polarized illuminations. The proposed cost‐effective and CMOS‐compatible material and methods open up an avenue for on‐chip development of numerous new phenomena with high efficiency in the visible domain.
Emerging roles of allosteric modulators in the regulation of protein‐protein interactions (PPIs): A new paradigm for PPI drug discovery
Authors: Ni Duan , Lu Shaoyong , Zhang Jian
Published: April 2019

Protein‐protein interactions (PPIs) are closely implicated in various types of cellular activities and are thus pivotal to health and disease states. Given their fundamental roles in a wide range of biological processes, the modulation of PPIs has enormous potential in drug discovery. However, owing to the general properties of large, flat, and featureless interfaces of PPIs, previous attempts have demonstrated that the generation of therapeutic agents targeting PPI interfaces is challenging, rendering them almost “undruggable” for decades. To date, rapid progress in chemical and structural biology techniques has promoted the exploitation of allostery as a novel approach in drug discovery. By attaching to allosteric sites that are topologically and spatially distinct from PPI interfaces, allosteric modulators can achieve improved physiochemical properties. Thus, allosteric modulators may represent an alternative strategy to target intractable PPIs and have attracted intense pharmaceutical interest. In this review, we first briefly introduce the characteristics of PPIs and then present different approaches for investigating PPIs, as well as the latest methods for modulating PPIs. Importantly, we comprehensively review the recent progress in the development of allosteric modulators to inhibit or stabilize PPIs. Finally, we conclude with future perspectives on the discovery of allosteric PPI modulators, especially the application of computational methods to aid in allosteric PPI drug discovery.
Identifying and characterizing treatment‐resistant schizophrenia in observational database studies
Authors: Jönsson Linus , Simonsen Jacob , Brain Cecilia , Kymes Steven , Watson Louise
Published: April 2019

Objectives

Treatment‐resistant schizophrenia (TRS) is clinically defined as failure to respond to two antipsychotics of adequate dose and duration. An algorithm (registry TRS) was developed, for identifying patients with TRS in claim datasets from Sweden and the United States.

Methods

Schizophrenia (SZ) patients aged ≥13 years were identified in both datasets and matched to controls. Patients were identified as having TRS by use of the registry TRS or ≥1 prescription for clozapine or use of other published criteria. The algorithm was compared for sensitivity, and patients with and without TRS were compared for psychiatric and hospital burden and Global Assessment of Functioning (GAF) scores. TRS prevalence was not assessed due to lack of clinically validated data to test the specificity of the algorithm.

Results

Swedish registry TRS patients ≤45 years at first SZ diagnosis had significantly lower GAF scores and earlier disease onset than non‐TRS patients. SZ patients with higher psychiatric comorbidity and hospital burden were more likely identified as TRS by all algorithms. The registry algorithm was significantly more sensitive to multiple inpatient stays and all psychiatric comorbidities at identifying TRS.

Conclusion

The registry algorithm appeared more sensitive at identifying patients with TRS, who had greater psychiatric and hospital burden.
Seasonal and pharmaceutical‐induced changes in selenoprotein glutathione peroxidase 4 activity in the reproductive dynamics of the soil biosentinel Podarcis sicula (Chordata: Reptilia)
Authors: Guerriero Giulia , Parisi Costantino , Abdel‐Gawad Fagr Kh. , Hentati Olfa , D'Errico Gerardino
Published: April 2019

There is rising concern for the interaction of environmental contaminants with brain transcriptome and the potential effect on reproductive processes. The present study sought to determine selenoprotein glutathione peroxidase 4 (gpx4) transcriptional activity in the brain and testis of the soil biosentinel, Podarcis sicula, through the main phases of the reproductive cycle and whether pharmaceuticals exert an endocrine disruption. Based on gpx4 cloned amminoacids sequence (GenBank AEX09236.1.), we used a bioinformatic approach to assess the structural role. Specifically, we detected seasonally the reactive oxygen species (ROS) level using electron spin resonance spectroscopy and gpx4 transcriptional activity using quantitative real‐time polymerase chain reaction. In addition, the impact of pharmaceuticals was assessed after 21‐days of treatment with ICI 182,780 and human chorionic gonadotropin administration in mating and winter stasis, respectively. Bioinformatic data shows the gpx4 proteic activity and a phylogenetic profile. ROS contents in lizard brain are significantly less than in testis and display higher levels after treatments. Brain gpx4 expression gives statistically significant seasonal differences, opposite trends in testis and altered expression in both tissues, with evidence of testis morphological and DNA disruption. Taken together, these results provide direct evidence that gpx4 in P. sicula plays a seasonal regulatory role and may be a reliable biomarker for reproductive health toxicity screening.
Task‐based assessment of a convolutional neural network for segmenting breast lesions for radiomic analysis
Authors: Spuhler Karl D. , Ding Jie , Liu Chunling , Sun Junqi , Serrano‐Sosa Mario , Moriarty Meghan , Huang Chuan
Published: April 2019

Purpose

Radiomics allows for powerful data‐mining and feature extraction techniques to guide clinical decision making. Image segmentation is a necessary step in such pipelines and different techniques can significantly affect results. We demonstrate that a convolutional neural network (CNN) segmentation method performs comparably to expert manual segmentations in an established radiomics pipeline.

Methods

Using the manual regions of interest (ROIs) of an expert radiologist (R1), a CNN was trained to segment breast lesions from dynamic contrast‐enhanced MRI (DCE‐MRI). Following network training, we segmented lesions for the testing set of a previously established radiomics pipeline for predicting lymph node metastases using DCE‐MRI of breast cancer. Prediction accuracy of CNN segmentations relative to manual segmentations by R1 from the original study, a resident (R2), and another expert radiologist (R3) were determined. We then retrained the CNN and radiomics model using R3’s manual segmentations to determine the effects of different expert observers on end‐to‐end prediction.

Results

Using R1’s ROIs, the CNN achieved a mean Dice coefficient of 0.71 ± 0.16 in the testing set. When input to our previously published radiomics pipeline, these CNN segmentations achieved comparable prediction performance to R1’s manual ROIs, and superior performance to those of the other radiologists. Similar results were seen when training the CNN and radiomics model using R3’s ROIs.

Conclusion

A CNN architecture is able to provide DCE‐MRI breast lesion segmentations which are suitable for input to our radiomics model. Moreover, the previously established radiomics model and CNN can be accurately trained end‐to‐end using ground truth data provided by distinct experts.
Nonfragile reliable control for positive switched systems with actuator faults and saturation
Authors: Li Miao , Zhang Junfeng , Jia Xianglei , Yang Haoyue
Published: April 2019

This paper presents a nonfragile reliable control approach to positive switched systems with actuator faults and saturation. In order to guarantee the reliability of the controller, the controller gain matrix is chosen as the sum of a normal gain matrix and a gain perturbation matrix. A nonfragile reliable control is first proposed for the considered systems using a gain matrix decomposition technique. Then, the presented nonfragile control design approach is developed for the systems with exogenous disturbances. An approach to compute the normal gain matrix and the gain perturbation matrix is also provided. Under the obtained controller, the resulting closed‐loop systems are positive and L1‐gain stable. Meanwhile, all the states will stay inside a cone. All presented conditions are described via linear programming. Finally, two examples are provided to verify the effectiveness of the theory findings.
Novel ultrafiltration membranes with the least fouling properties for the treatment of veterinary antibiotics in the pharmaceutical wastewater
Authors: Bojaran Majid , Akbari Ahmad , Yunessnia lehi Arash
Published: April 2019

Dendrimers have received more attention in all fields of research these days. In the present study, polyamidoamine (PAMAM) dendrimers were synthesized on the acrylic ultrafiltration membranes to minimize fouling as an important deficiency in the separation process. The antifouling activity of these dendrimers with different generations (G0‐3) was tested to restrict three macrolides (tylvalosin, tylosin, and tulathromycin) and two pleuromutilins (tiamulin and valnemulin) as veterinary antibiotic drugs with amine groups and positive charges at pH = 7 of the membrane surface. These compounds are risky for human consumption. Due to having several amine functional groups and branches, PAMAM dendrimers can be a great coating agent for antifouling. G3 PAMAM dendrimer‐coated membranes had the best performance (water flux: 130.7 L/m2·h, rejection of tulathromycin: 91.4%, flux recovery ratio: 86.3%). The function of this ultrafiltration process depended on pore size and also charge surface. A significant reduction for irreversible and reversible fouling was observed for this new ultrafiltration membrane (Fir: 14.5%, Fre: 21.9%). This observation was confirmed by the power law model. Three 5‐hour cycle ultrafiltration processes were carried out for veterinary antibiotic wastewater that showed 3.18% loss of initial water flux (for the third cycle), final cleaning efficiency of 96.82%, and tylvalosin rejection of 94.1%.
A pilot evaluation of the social validity of a bullying bystander program adapted for high school students
Authors: Doumas Diana M. , Midgett Aida , Watts April D.
Published: April 2019

Although school‐based programs are effective at decreasing bullying, the majority of studies have been conducted with elementary and middle school students. We conducted a pilot study using a randomized controlled design investigating the social validity of a brief, bullying bystander program adapted to be age‐appropriate for high school students (N = 65). Results indicated that high school students in the intervention group perceived the program to be acceptable and relevant and reported greater increases in knowledge ( = 0.27) and confidence to intervene ( = 0.27) in bullying situations compared to students in the control group. Despite being trained in the use of four intervention strategies, students reported using two of the strategies infrequently. Additionally, we found a significant difference between the intervention and control group for only one strategy (Φ = −0.44). This study provides partial support for the social validity of the adapted program. Implications for implementing the program at the high school level are discussed.
Activation of cGMP/PKG/p65 signaling associated with PDE5‐Is downregulates CCL5 secretion by CD8+ T cells in benign prostatic hyperplasia
Authors: Jin Song , Xiang Peng , Liu Jie , Yang Yang , Hu Shuai , Sheng Jindong , He Qun , Yu Wei , Han Wenke , Jin Jie , Peng Jing
Published: April 2019

Background

Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men, but the underlying pathophysiological mechanisms are complex and not fully understood. Phosphodiesterase type 5 inhibitors (PDE5‐Is) used to treat BPH could upregulate the cyclic guanosine monophosphate (cGMP)‐dependent protein kinase G (PKG) signaling, which was shown to blunt inflammation in the prostate. Our previous findings indicate that CD8+ T cells promote the proliferation of BPH epithelial cells (BECs) in low androgen conditions through secretion of CCL5; however, the role of the cGMP/PKG pathway in the process is unclear.

Methods

Paraffin‐embedded tissues were used for expression quantity of CD8+ T cells, CCL5, cyclin D1, and PDE5 protein by immunohistology in prostate specimens which were/were not treated with finasteride 5 mg daily for at least 6 months before surgery. BPH‐1 cells were cocultured with or without CD8
+ T cells or PDE5‐Is in low androgen conditions for 4 days. The conditioned media, BPH‐1 cells, and CD8
+ T cells were harvested for the subsequent experiments. The quantitative polymerase chain reaction was used for assaying the level of messenger RNA expression of CCL5. CCL5 in the conditioned media was detected by the enzyme‐linked immunosorbent assay. The effect of PDE5‐Is on cocultured BPH‐1/CD8
+ T‐cell proliferation was detected by the cell counting kit‐8. A high‐fat diet (HFD)‐induced prostatic hyperplasia rat model was used to investigate the effect of cGMP/PKG activation in CD8
+ T cells in vivo.

Results

CD8+ T‐cell infiltration into human BPH tissues was positively correlated with the expression of CCL5, cyclin D1, and PDE5, whereas in an HFD‐induced prostatic hyperplasia rat model, the activation of the cGMP/PKG signaling by a PDE5‐I could suppress the CD8
+ T‐cell infiltration and the CCL5 and cyclin D1 expression. Furthermore, the activation of the cGMP/PKG pathway inhibited CCL5 secretion by CD8
+ T cells by downregulating nuclear factor‐κB p65 phosphorylation, which reduced the growth of BPH‐1 through CCL5/STAT5/CCND1 signaling.

Conclusions

Our results indicate that the upregulation of the cGMP/PKG/p65 signaling reduces CCL5 secretion in CD8
+ T cells, which in turn decreases the proliferation of BECs in low androgen conditions, suggesting that the combination of 5α reductase inhibitors lowering androgen levels and PDE5‐Is may be a novel, more effective treatment for BPH patients.
Protein kinase D1 induces G1‐phase cell‐cycle arrest independent of Checkpoint kinases by phosphorylating Cell Division Cycle Phosphatase 25
Authors: Nickkholgh Bita , Sittadjody Sivanandane , Ordonez Karina , Rothberg Michael Bryan , Balaji K. C.
Published: April 2019

Protein Kinase D1 (PrKD1) functions as a tumor and metastasis suppressor in several human cancers by influencing cell‐cycle progression. However, the exact mechanism of cell‐cycle regulation by PrKD1 is unclear. Overexpression and ectopic expression of PrKD1 induces G1 arrest in cancer cell lines. Because checkpoint kinases (CHEKs) are known to play a role in progression through the G1 phase, we downregulated CHEK1, which did not overcome the G1 arrest induced by PrKD1. Using in vitro phosphorylation and Western blot assays, we showed that PrKD1 phosphorylates all CDC25 isoforms (known substrates of CHEK kinases), independent from CHEK kinases, suggesting that direct phosphorylation of CDC25 by PrKD1 may be an alternate mechanism of G1 arrest. The study has identified a molecular mechanism for the influence of PrKD1 in cell‐cycle progression.
Benzimidazole‐Substituted Indolo[3,2‐b]carbazoles: Acid‐Responsive Probes
Authors: Kadam Vinay S. , Bhatt Prachi A. , Karmakar Himadri S. , Zade Sanjio S. , Patel Arun L.
Published: April 2019

Benzimidazole substituted indolo[3,2‐b]carbazole derivatives (5 and 6) were synthesized by formylation of N,N′‐dioctylindolo[3,2‐b]carbazole followed by reaction with o‐phenyelene diamine. The structures of these two compounds were characterized by high resolution mass‐spectrometry (HRMS) and NMR (1H and 13C) spectroscopy. Their photophysical and electrochemical properties were studied by absorption and emission spectroscopy and cyclic voltammetry. Compounds 5 and 6 showed sensitivity towards acid in solution as well as in the solid state. Density functional theory (DFT) studies showed that compound 5 is more planar compared to 6. Frontier molecular orbitals (FMO) analysis suggested that photoinduced electron transfer (PET) from indolo[3,2‐b]carbazole moiety (fluorophore) to the protonated benzimidazole unit results in quenching.
A Kinetic Study of the Intramolecular Nitroaldol (Henry) Reaction Giving 2‐Nitroindan‐1‐ols
Authors: Horáková Eva , Valtr Jakub , Dostálová Kamila , Drabina Pavel , Váňa Jiří , Růžička Aleš , Hanusek Jiří
Published: April 2019

An intramolecular base‐catalyzed nitroaldol reaction of three newly prepared 2‐(2‐nitroalkyl)benzaldehydes (1a‐c) giving corresponding 2‐nitroindan‐1‐ols (2a‐c) was studied in water and five non‐aqueous solvents. Whilst for the parent 2‐(2‐nitroethyl)benzaldehyde (1a) the reaction takes place in two kinetically discernible steps – deprotonation and cyclization, for 2‐(2‐nitropropyl)‐ and 2‐(2‐nitro‐2‐phenylethyl)benzaldehydes 1b and 1c general base‐catalyzed formation of a reactive carbanion is rate‐limitting. An unusually high Brønsted coefficient (βB=1.12 ± 0.03) was found for 1b indicating smaller imbalance of the transition state whose structure therefore resembles a nitronate. Cyclization products 2a‐c prefer relative trans‐configuration in ratios from 55:45 to 83:17 depending on the solvent. Mutual interconversion of the cis‐/trans‐diastereoisomers occurs either via nitronate species 2a– or via a reverse ring opening/ring closing pathway through the nitronate species 1b– and 1c–. The mechanism was also supported by quantum calculations.
Unveiling the Interfacial Effects for Enhanced Hydrogen Evolution Reaction on MoS2/WTe2 Hybrid Structures
Authors: Zhou Yu , Pondick Joshua V. , Silva Jose Luis , Woods John M. , Hynek David J. , Matthews Grace , Shen Xin , Feng Qingliang , Liu Wen , Lu Zhixing , Liang Zhixiu , Brena Barbara , Cai Zhao , Wu Min , Jiao Liying , Hu Shu , Wang Hailiang , Araujo Carlos Moyses , Cha Judy J.
Published: April 2019

Using the MoS2‐WTe2 heterostructure as a model system combined with electrochemical microreactors and density function theory calculations, it is shown that heterostructured contacts enhance the hydrogen evolution reaction (HER) activity of monolayer MoS2. Two possible mechanisms are suggested to explain this enhancement: efficient charge injection through large‐area heterojunctions between MoS2 and WTe2 and effective screening of mirror charges due to the semimetallic nature of WTe2. The dielectric screening effect is proven minor, probed by measuring the HER activity of monolayer MoS2 on various support substrates with dielectric constants ranging from 4 to 300. Thus, the enhanced HER is attributed to the increased charge injection into MoS2 through large‐area heterojunctions. Based on this understanding, a MoS2/WTe2 hybrid catalyst is fabricated with an HER overpotential of −140 mV at 10 mA cm−2, a Tafel slope of 40 mV dec−1, and long stability. These results demonstrate the importance of interfacial design in transition metal dichalcogenide HER catalysts. The microreactor platform presents an unambiguous approach to probe interfacial effects in various electrocatalytic reactions.
Scalable Nanoshaping of Hierarchical Metallic Patterns with Multiplex Laser Shock Imprinting Using Soft Optical Disks
Authors: Jin Shengyu , Zhou Zhiguang , Sakr Enas Said Attia , Motlag Maithilee , Huang Xinyu , Tong Lei , Bermel Peter , Ye Lei , Cheng Gary J.
Published: April 2019

Large‐area patterning of metals in nanoscale has always been a challenge. Traditional microfabrication processes involve many high‐cost steps, including etching and high‐vacuum deposit, which limit the development of functional nanostructures, especially multiscale metallic patterns. Here, multiplex laser shock imprinting (MLSI) process is introduced to directly manufacture hierarchical micro/nanopatterns at a high strain rate on metallic surfaces using soft optical disks with 1D periodic trenches as molds. The unique metal/polymer layered structures in inexpensive soft optical disks make them strong candidates of molds for MLSI processes. The feasibility of MLSI on hard metals toward soft molds is studied using theoretical simulation. In addition, various types of hierarchical structures are fabricated via MLSI, and their optical reflectance can be modulated via a combination of depth (laser power density), width (types of molds), and angles (rotation between molds). The optical properties have been studied with surface plasmon polariton modes theory. This work opens a new way of manufacturing hierarchical micro/nanopatterns on metals, which is promising for future applications in fields of plasmonics and metasurfaces.
Directional Fano Resonance in an Individual GaAs Nanospheroid
Authors: Ma Churong , Yan Jiahao , Huang Yingcong , Yang Guowei
Published: April 2019

Fano resonance has been observed in a wide variety of nanophotonic structures such as photonic crystals, plasmonic structures, and metamaterials. It arises from the interference of discrete resonance states with broadband continuum states. As an emerging nanophotonic material, high‐index all‐dielectric nanomaterials provide a new platform to achieve Fano resonance by virtue of the simultaneous excited electric and magnetic resonances. However, to date, Fano resonance in the visible region has not been observed in individual high‐index all‐dielectric nanoparticles. Here, for the first time, the experimental observation of the directional Fano resonance is reported in an individual GaAs nanospheroid. The special geometry enables GaAs nanospheroids to generate spectrally overlapped electric and magnetic dipole resonances, which enhances their spectral coupling, giving rise to asymmetric‐shaped backward scattering spectrum. This directional Fano resonance can be tuned by the aspect ratio of nanospheroids as well as excitation polarization. In addition, efficient directional light scattering is realized at the total scattering peak of the GaAs nanospheroid. The forward‐to‐backward scattering ratio can be largely enhanced due to Fano dip in the backward scattering spectrum. These findings suggest that high‐index all‐dielectric nanospheroid is a promising candidate for directional sources and optical switches.
Oriented Polarization Tuning Broadband Absorption from Flexible Hierarchical ZnO Arrays Vertically Supported on Carbon Cloth
Authors: Wang Lei , Li Xiao , Li Qingqing , Yu Xuefeng , Zhao Yunhao , Zhang Jie , Wang Min , Che Renchao
Published: April 2019

A novel strategy is used to design large‐scale polarized carbon‐based dielectric composites with sufficient interaction to electromagnetic waves. Highly uniform polar zinc oxide arrays are vertically grown on a flexible conductive carbon cloth substrate (CC@ZnO) via an in situ orientation growth process. Anion regulation is found to be a key factor to the morphology of hierarchical ZnO arrays including single‐rod, cluster and tetrapod‐shaped. As a typical dielectric loss hybrid composite, the electromagnetic parameters of the CC@ZnO system and charge density distribution in polarized ZnO rods confirm that the 3D intertwined carbon cloth is used as a conductive network to provide ballistic electron transportation. Moreover, the defect‐rich ZnO arrays are well in contact with the CC substrate, favoring interface polarization, multiscattering, as well as impedance matching. Surprisingly, the efficient absorption bandwidth of the CC@ZnO‐1 composite can reach 10.6 GHz, covering all X and Ku bands. The oriented ZnO possesses oxygen vacancies and exposure to a large amount of intrinsic polar surfaces, encouraging the polarization behavior under microwave frequency. Optimized CC@ZnO materials exhibit fast electron transportation, strong microwave energy dissipation, and superior wide absorption. The results suggest that the CC@ZnO composites have promising potential as flexible, tuning, and broadband microwave absorbers.
Electrochemically Driven Coordination Tuning of FeOOH Integrated on Carbon Fiber Paper for Enhanced Oxygen Evolution
Authors: Han Xiaotong , Yu Chang , Yang Juan , Song Xuedan , Zhao Changtai , Li Shaofeng , Zhang Yan , Huang Huawei , Liu Zhibin , Huang Hongling , Tan Xinyi , Qiu Jieshan
Published: April 2019

Coordination tuning of catalysts is a highly effective strategy for activating and improving the intrinsic activity. Herein, a Co‐engineered FeOOH catalyst integrated on carbon fiber paper (Co‐FeOOH/CFP) is reported, which realized a great improvement of the oxygen evolution activity by tuning the coordination geometry of the Fe species with an electrochemically driven method. Experiments and theoretical calculation demonstrate that the FeO bonds of FeOOH are partially broken, which is rooted in the Co incorporation, thus resulting in unsaturated FeO6 ligand structures and a relatively narrow bandgap. Consequently, the reorganized Fe sites on the surface show an enhanced capability for adsorbing OH− species and the Co‐FeOOH exhibits an improved conductivity. As expected, the Co‐FeOOH/CFP hybrids exhibit an extremely low overpotential of ≈250 mV at 10 mA cm−2 and a small Tafel slope, which far outperforms that of electrochemically sluggish FeOOH. The present work emphasizes the importance of local Fe coordination in catalysis and provides an in‐depth insight into the mechanism of the enhanced catalytic activity.
Interlayer Hydrogen‐Bonded Metal Porphyrin Frameworks/MXene Hybrid Film with High Capacitance for Flexible All‐Solid‐State Supercapacitors
Authors: Zhao Weiwei , Peng Jiali , Wang Weikang , Jin Beibei , Chen Tiantian , Liu Shujuan , Zhao Qiang , Huang Wei
Published: April 2019

2D metal‐porphyrin frameworks (MPFs) are attractive for advanced energy storage devices. However, the inferior conductivity and low structural stability of MPFs seriously limit their application as flexible free‐standing electrodes with high performance. Here, for the first time, an interlayer hydrogen‐bonded MXene/MPFs film is proposed to overcome these disadvantages by intercalation of highly conductive MXene nanosheets into MPFs nanosheets via a vacuum‐assisted filtration technology. The alternant insertion of MXene and MPFs affords 3D interconnected “MPFs‐to‐MXene‐to‐MPFs” conductive networks to accelerate the ionic/electronic transport rates. Meanwhile, the interlayer hydrogen bonds (F···HO and O···HO) contribute a high chemical stability due to a favorable tolerance to volume change caused by phase separation and structural collapse during the charge/discharge process. The synergistic effect makes MXene/MPFs film deliver a capacitance of 326.1 F g−1 at 0.1 A g−1, 1.64 F cm−2 at 1 mA cm−2, 694.2 F cm−3 at 1 mA cm−3 and a durability of about 30 000 cycles. The flexible symmetric supercapacitor shows an areal capacitance of 408 mF cm−2, areal energy density of 20.4 µW h cm−2, and capacitance retention of 95.9% after 7000 cycles. This work paves an avenue for the further exploration of 2D MOFs in flexible energy storage devices.
Effect of Cooling Rate on Oxide Inclusions During Solidification of 304 Stainless Steel
Authors: Wang Yi , Yang Wen , Zhang Lifeng
Published: April 2019

Laboratory experiments are carried out to investigate the effect of cooling rate on oxide inclusions during the solidification of Si‐Mn killed 304 stainless steel. The oxide inclusions in the 304 stainless steel were Al2O3‐SiO2‐CaO‐MnO‐MgO system. During the cooling process, the change of inclusions is supposed to consist of two steps. The first step is the precipitation and growth of SiO2‐MnO‐Al2O3 type inclusions during the solidification process of steel. The second step is the transformation of inclusions into the MnO‐Cr2O3‐Al2O3 system in solid steel by the interaction between inclusions and the steel matrix. Smaller cooling rate led to the more complete growth and transformation of inclusions. With decreasing the cooling rate, the number of large inclusions increased while that of small inclusions decreased. Meanwhile, the diameter of the inclusions increased. The main reason for the size difference of inclusions at different cooling rates is the difference of inclusion growth during solidification.
Morphometric, phylogenetic and biogeographic analyses ofPyrularia(Santalales), a parasitic disjunct lineage between eastern Asia and eastern North America
Authors: Zhou Zhuo , Hu Jin‐Jin , Wen Jun , Sun Hang
Published: April 2019

Pyrulariais a small parasitic genus of the Santalales with two to five species exhibiting a well‐known classical intercontinental disjunct distribution between eastern Asia (EA) and eastern North America (ENA).Pyrulariaand another santalaceous genusBuckleyarepresent the only two parasitic plant lineages with the EA–ENA disjunction. The present study was carried out to assess the species number and molecular and morphological differentiation inPyrularia, and to reconstruct the biogeography of thePyrulariaclade (Pyrulariaand its close allies) using dating and biogeographic inferences. A phylogenetic analysis based on two nuclear and seven plastid markers strongly supported the monophyly ofPyrulariaand revealed two highly distinct subclades corresponding to EA and ENA within the genus. Incongruent topologies within the eastern Asian lineage were found between the nuclear and the plastid datasets, which may be attributed to incomplete lineage sorting. Morphometric and phylogenetic analyses suggest thatPyrulariain eastern Asia may best be treated as a single species,P. edulis. Molecular dating based on four markers suggested that the divergence time between the intercontinental species was in the late Miocene at 5.58 Ma (95% HPD: 2.08–11.72 Ma), which was close to the split of the trans‐Pacific clades within the other parasitic EA–ENA disjunct genusBuckleya. The EA–ENA disjunction in the only two parasitic genera may have resulted from the fragmentation of the mesophytic temperate forests in the late Miocene. ThePyrulariaclade (including the close allies ofPyrularia) was inferred to have originated in Africa, then dispersed to Asia, and subsequently to North America via the Bering land bridge, resulting in the current intercontinental EA–ENA distribution ofPyrularia.