bluuebunny/crossref_metadata_2025 huggingface dataset:
Creating Conditions for Literate Engagement: Teaching, Learning, and Acting in the World
Authors: Burns Leslie David , Faris Amber , Melino Flor , Turner Wendy , Wheatley Abigail
Published: May 2019

The authors illustrate how literacy and language arts teachers work with students to help them act and engage as agents in and beyond school. The authors demonstrate how teachers design environments for learning and practice and how young people use resulting skills and motivations intentionally as a result of their experiences in those environments. With certain conditions in place, students learn to engage purposefully as leaders their communities. The authors offer examples of how teachers help students engage in literate practices, demonstrate how young people think about literacy in their lives, and celebrate how students use their learning to attain their goals beyond academic achievement. The authors conclude by noting how systematic design of engaging school spaces reflects research‐based findings about literacy engagement in high school classrooms, encouraging teachers to create conditions for engagement purposefully to support all youths in all contexts for similar success.
Effective control of biofilms by photothermal therapy using a gold nanorod hydrogel
Authors: Bermúdez‐Jiménez Carlos , Niño‐Martínez Nereyda , Patiño‐Marín Nuria , Martínez‐Gutiérrez Fidel , Ruiz Facundo , Bach Horacio , Martínez‐Castañón Gabriel
Published: May 2019

Biofilms are matrices synthesized by bacteria containing polysaccharides, DNA, and proteins. The development of biofilms in infectious processes can induce a chronic inflammatory response that may progress to the destruction of tissues. The treatment of biofilms is difficult because they serve as a bacterial mechanism of defense and high doses of antibiotics are necessary to treat these infections with limited positive results. It has been demonstrated that photothermal therapy using gold nanorods (AuNRs) is an attractive treatment because of its anti‐biofilm activity. The purpose of this work was to generate a novel chitosan‐based hydrogel embedded with AuNRs to evaluate its anti‐biofilm activity. AuNRs were synthesized by the seed‐mediated growth method and mixed with the chitosan‐based hydrogel. Hydrogels were characterized and tested against two bacterial strains by irradiating the produced biofilm in the presence of the nanoformulation with a laser adjusted at the near infrared spectrum. In addition, the safety of the nanoformulation was assessed with normal human gingival fibroblasts. Results showed that a significant bacterial killing was measured when biofilms were exposed to an increase of 10°C for a short time of 2 min. Moreover, no cytotoxicity was measured when normal gingival fibroblasts were exposed to the nanoformulation using the bactericidal conditions. The development of the reported formulation can be used as a direct application to treat periodontal diseases or biofilm‐produced bacteria that colonize the oral cavity.
The influence of the Chuyou Yuyang granule on the Toll‐like receptor/nuclear factor‐κB signal pathway in Helicobacter pylori‐positive peptic ulcer patients
Authors: Yang Fang , Ge Guiping , Shen Wen , Chen Liang
Published: May 2019

Background

The cure rate of Helicobacter pylori (HP)‐positive peptic ulcer has appeared to downward trend, and the resistance of the ulcer relapse has become a hot issue.

Methods

Hematoxylin and eosin staining was used to detect the repair of the damaged tissues in patients after treatment with the Chuyou Yuyang granule (CYYY). Elisa was used to analyze the expression of cytokine interleukin 18 (IL‐18) and tumor necrosis factor α (TNF‐α) in the patients' serum. Western blot analysis was used to explore the mechanism of the CYYY. Reverse‐transcription polymerase chain reaction (RT‐PCR) was used to detect the expression of microRNA‐155a (miR‐155a) and miR‐146a in the blood of the patients and to confirm whether CYYY could cure peptic ulcer through regulation of miR‐155a and miR‐146a.

Results

The damaged gastric mucosal tissues of ulcer patients were significantly repaired by treating with CYYY. The pro‐inflammatory cytokine IL18 and TNF‐α were notably repressed after treating with CYYY. In addition, CYYY played a key role in regulation of the Toll‐like receptor (TLR4)/nuclear factor‐κB (NF‐κB) signal pathway and the expression of miR‐155a and miR‐146a.

Conclusion

CYYY was a highly effective therapeutic method for peptic ulcer patients by inhibiting the activation of the TLR4/NF‐κB signal pathway and suppressing the expression of miR‐155a and miR‐146a.
Breviscapine provides a neuroprotective effect after traumatic brain injury by modulating the Nrf2 signaling pathway
Authors: Li Fayin , Wang Xiaodong , Zhang Zhijie , Gao Pengfei , Zhang Xianlong
Published: May 2019

Breviscapine (BVP) has been widely used in the treatment of several systemic diseases, including those of the cardiovascular and cerebrovascular systems. But, few studies have looked at the neuroprotective effects of BVP and its potential effect in treating traumatic brain injury (TBI). The present study investigated the neuroprotective effect of BVP following TBI and illuminated the underlying mechanism. The weight drop‐induced closed diffuse traumatic brain injury method was used to induce TBI in rats. BVP was injected intraperitoneally 30 minutes after TBI. Neurologic scores were performed to measure behavioral outcomes. Nissl staining and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL) assays were performed on histopathologic tissue sections to evaluate neuronal apoptosis. The nuclear factor erythroid 2‐related factor 2 (Nrf2) and its related downstream proteins, including heme oxygenase‐1 (HO‐1) and quinine oxidoreductase‐1 (NQO1) were detected with Western blots. BVP treatment alleviated or attenuated TBI‐induced neuron cell apoptosis and improved neurobehavioral functions through the upregulated expression of Nrf2 and its related downstream proteins. This study, using the drug, BVP, we present new mechanisms responsible for neuronal apoptosis in TBI with possible involvement of the Nrf2 pathway.
Cancer drug resistance: A fleet to conquer
Authors: Hussain Showket , Singh Ankita , Nazir Sheeraz Un , Tulsyan Sonam , Khan Asiya , Kumar Ramesh , Bashir Nasreena , Tanwar Pranay , Mehrotra Ravi
Published: May 2019

Cancer is a disease that claims millions of lives each year across the world. Despite advancement in technologies and therapeutics for treating the disease, these modes are often found to turn ineffective during the course of treatment. The resistance against drugs in cancer patients stems from multiple factors, which constitute genetic heterogeneity like gene mutations, tumor microenvironment, exosomes, miRNAs, high rate of drug efflux from cells, and so on. This review attempts to collate all such known and reported factors that influence cancer drug resistance and may help researchers with information that might be useful in developing better therapeutics in near future to enable better management of several cancers across the world.
microRNA‐199a‐5p suppresses glioma progression by inhibiting MAGT1
Authors: Wang Guang , Li Yong , Li Jie , Zhang Dongxia , Luo Chao , Zhang Bingqian , Sun Xiaochuan
Published: May 2019

microRNAs (miRNAs) can function as a tumor suppressor or oncogenic genes in human cancers. Alternation expression of miR‐199a‐5p has been revealed in several human cancers. However, its expression pattern and biological roles in glioma remain unclear. Expression levels of miR‐199a‐5p in glioma were evaluated at first. The effects of miR‐199a‐5p expression on cell proliferation, migration, and invasion were investigated using the MTT assay, wound‐healing assay, and transwell invasion assay. The expression of miR‐199a‐5p was found to be reduced in glioma cell lines. Overexpression of miR‐199a‐5p inhibits glioma cell proliferation, migration, and invasion in vitro. Furthermore, the target of miR‐199a‐5p was predicted by TargetScan and validated by luciferase activity reporter assay. We found magnesium transporter 1 (MAGT1) was a direct target of miR‐199a‐5p. Overexpression of MAGT1 reversed the effects of miR‐199a‐5p on glioma cell behaviors. Taken together, our study revealed that miR‐199a‐5p and MAGT1 have the potential to be used as a biomarker for glioma.
Identification of prognostic biomarkers for breast cancer based on miRNA and mRNA co‐expression network
Authors: Yao Yan , Liu Ruijuan , Gao Chundi , Zhang Tingting , Qi Lingyu , Liu Gongxi , Zhang Wenfeng , Wang Xue , Li Jie , Li Jia , Sun Changgang
Published: May 2019

Purpose

Breast cancer (BC) remains a serious health threat for women due to its high incidence and the trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) could play important roles in various biological processes involved in the pathogenesis of BC. The present study aimed to identify potential prognostic biomarkers associated with BC.

Methods

Here, original gene expression profiles of patients with BC was downloaded from The Cancer Genome Atlas (TCGA) database. TargetScan, miRDB, and miRTarBase databases were used to predict the target genes of prognostic‐related differentially expressed miRNAs (DEMs). Subsequently, functional enrichment analysis and topological analysis were performed on the overlaps of target genes and differentially expressed mRNAs (DEGs), and Kaplan‐Meier analysis was used to predict prognosis‐related target genes to identify prognostic biomarkers.

Results

A total of 218 DEMs and 2222 DEGs were extracted in which eight miRNAs were associated with prognosis, and 278 target DEGs were screened out incorporated into functional enrichment analysis and protein‐protein interaction network visualization studies. Additionally, five hub genes (CXCL12, IGF1, LEF1, MMP1, and RACGAP1) were observed as potential biomarkers for BC prognosis through survival analysis.

Conclusion

We performed a distinctive correlation analysis of miRNA‐mRNA in BC patients, and identified eight miRNAs and five hub genes may be effective biomarkers for the prognosis of BC patients.
Integrative analyses of key genes and regulatory elements in fluoride‐affected osteosarcoma
Authors: Li Mi , Jin Xin , Guo Fengjing , Wu Gang , Wu Lin , Deng Sisi
Published: May 2019

Osteosarcoma is one of the most malignant tumors in adolescents with severe outcomes while fluoride is one of the most abundant elements in the environment. Epidemiological evidence has elucidated the relationship between fluoride and osteosarcoma, but the molecular mechanisms are extremely complicated. Microarray profiles were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in the progression of fluoride‐affected osteosarcoma. The functional enrichment analysis was performed, a protein‐protein interaction network, a microRNA‐messenger RNA (mRNA) and a transcription factors‐mRNA regulatory network were constructed and performed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. A total of 171 DEGs were identified. The functions and pathways of the DEGs were enriched in nucleolus, protein ubiquitination, protein binding, RNA transport, and the spliceosome. Eighteen hub genes were identified and functional analysis revealed that these genes are mainly enriched in protein binding, nucleoplasm, and ribosomal RNA processing. Survival analysis showed that the hub genes may be involved in the invasion or recurrence of osteosarcoma. In conclusion, the DEGs and hub genes with their regulatory elements identified in this study will help us understand the molecular mechanisms underlying fluoride‐affected osteosarcoma and provide candidate targets for future research.
Effective and new potent drug combination: Histone deacetylase and Wnt/β‐catenin pathway inhibitors in lung carcinoma cells
Authors: Akgun Oguzhan , Erkisa Merve , Ari Ferda
Published: May 2019

Lung cancer is the most commonly diagnosed cancer worldwide with a high mortality rate. In this study, the therapeutic effect of combination valproic acid and niclosamide was investigated on human lung cancer cell line. The effects of the compounds alone and combination therapy on cell viability were determined by sulforhodamine B and adenosine 5′‐triphosphate viability assays. Flow cytometry was used to determine the cell death mechanism and DNA damage levels responsible for the cytotoxic effects of combination therapy. The presence of apoptosis in cells was supported by fluorescence microscopy and also by using inhibitors of the apoptotic signaling pathway. The increase in cellular reactive oxygen species (ROS) level in combination therapy was determined by H2DCFDA staining. The effect of N‐acetyl‐l‐cysteine combination on ROS increase was investigated on cell viability. In addition, the expression levels of the proteins associated with epigenetic regulation and cell death were analyzed by Western blotting and gene expression levels were determined using real‐time quantitative polymerase chain reaction.It was observed that the combination therapy showed a cytotoxic effect on the A549 lung cancer cells compared to the individual use of the inhibitors. The absence of this effect on normal lung cells revealed the presence of a selective toxic effect. When the mechanism of cytotoxicity is examined, it has been observed that combination therapy initiates the activation of tumor necrosis receptors and causes apoptosis by activated caspase. It was also observed that this extrinsic apoptotic pathway was activated on the mitochondrial pathway. In addition, ER stress and mitochondrial membrane potential loss associated with increased ROS levels induce cell death. When the data in this study were evaluated, combination therapy caused a dramatic decrease in cell viability by inducing the extrinsic apoptotic pathway in lung cancer cell line. Therefore, it was concluded that it can be used as an effective and new treatment option for lung cancer.
Modulation of miR‐34a in curcumin‐induced antiproliferation of prostate cancer cells
Authors: Zhu Mingming , Zheng Zongmei , Huang Jiaming , Ma Xiao , Huang Cong , Wu Rui , Li Xiaoting , Liang Zhaofeng , Deng Feifei , Wu Jieshu , Geng Shanshan , Xie Chunfeng , Zhong Caiyun
Published: May 2019

Curcumin is a phytochemical which exhibits significant inhibitory effect in multiple cancers including prostate cancer. MicroRNA‐34a (miR‐34a) was found to be a master tumor suppressor miRNA and regulated the growth of cancer cells. To date, however, the role of miR‐34a in the anticancer action of curcumin against prostate cancer has been rarely reported. In the present study, we showed that curcumin altered the expression of cell cycle‐related genes (cyclin D1, PCNA, and p21) and inhibited the proliferation of prostate cancer cells. Furthermore, we found that curcumin significantly upregulated the expression of miR‐34a, along with the downregulated expression of β‐catenin and c‐myc in three prostate cancer cell lines. Inhibition of miR‐34a activated β‐catenin/c‐myc axis, altered cell cycle‐related genes expression and significantly suppressed the antiproliferation effect of curcumin in prostate cancer cells. Findings from this study revealed that miR‐34a plays an important role in the antiproliferation effect of curcumin in prostate cancer.
Introduction of a bounded penalty function in contact‐assisted simulations of protein structures to omit false restraints
Authors: Lubecka Emilia A. , Liwo Adam
Published: May 2019

Contact‐assisted simulations, the contacts being predicted or determined experimentally, have become very important in the determination of the structures of proteins and other biological macromolecules. In this work, the effect of contact‐distance restraints on the simulated structures was investigated with the use of multiplexed replica exchange simulations with the coarse‐grained UNRES force field. A modified bounded flat‐bottom restraint function that does not generate a gradient when a restraint cannot be satisfied was implemented. Calculations were run with (i) a set of four small proteins, with contact restraints derived from experimental structures, and (ii) selected CASP11 and CASP12 targets, with restraints as used at prediction time. The bounded penalty function largely omitted false contacts, which were usually inconsistent. It was found that at least 20% of correct contacts must be present in the restraint set to improve model quality with respect to unrestrained simulations. © 2019 Wiley Periodicals, Inc.
Investigation of the direct electrochemistry and electrocatalysis of myoglobin on gold nanorods modified electrode
Authors: Yin Chunxiao , Weng Wenju , Gao Rui , Liu Juan , Niu Yanyan , Li Guangjiu , Sun Wei
Published: May 2019

Direct electrochemistry and electrocatalysis of myoglobin (Mb) on a gold nanorod (AuNR)‐decorated carbon ionic liquid electrode (CILE) were studied in this article. The fabricated Nafion/Mb/AuNRs/CILE was used as an electrochemical biosensor for determining trichloroacetic acid (TCA) and sodium nitrite (NaNO2). AuNRs exhibited high metal conductivity, and acted as the bridge between electrochemical active centers of Mb and the substrate electrode with the electron transfer rate accelerated. Electrochemical performances of Nafion/Mb/AuNRs/CILE were checked in pH 3.0 phosphate buffer solution with the electrochemical parameters calculated. Low detection limits and wide linear ranges were obtained in electrocatalytic investigations of different catalytic substrates including TCA and NaNO2, which exhibited potential applications in actual sample detection.
One‐pot, fast cyclopropanation reaction of indandione with various aldehydes in the presence of cyanogen bromide and trimethylamine
Authors: Aalinejad Michael , Noroozi Pesyan Nader
Published: May 2019

A new, fast, and easy one‐pot cyclopropanation reaction of aromatic and aliphatic aldehydes with 1H‐indene‐1,3(2H)‐dione and cyanogen bromide (BrCN) was developed for synthesizing 3′‐(aryl[alkyl])‐dispiro[indan‐2,1′‐cyclopropane‐2′,2′′‐indan]‐1,1′′,3,3′′‐tetrone in excellent yields in a short time (about 15 s) under basic media. All structures were characterized using IR, 1H NMR, and 13C NMR spectroscopy techniques.
An illustration of collaborative care with a focus on the role of fathers in Maudsley Anorexia Nervosa Treatment for Adults (MANTRA)
Authors: Treasure Janet , Schmidt Ulrike , Kan Carol
Published: May 2019

The aim of this case study is to illustrate the importance of collaborative care as part of Maudsley Anorexia Nervosa Treatment for Adults (MANTRA). Mothers are often at the foreground of providing support within the family. However, fathers have the potential to play a profound role. In this paper, we describe a patient with anorexia nervosa treated with the MANTRA. The formulation of this case included autistic spectrum traits in both the father and daughter leading to social isolation. We describe how the family members were engaged into treatment and how paternal support was used to promote social connection and an improved quality of life in the daughter. Some details of the case have been altered to maintain confidentiality.
Th17 immune response to adipose tissue‐derived mesenchymal stromal cells
Authors: Najar Mehdi , Lombard Catherine A. , Fayyad‐Kazan Hussein , Faour Wissam H. , Merimi Makram , Sokal Etienne M. , Lagneaux Laurence , Fahmi Hassan
Published: May 2019

Adipose tissue‐derived mesenchymal stromal cells (ASCs) hold the promise of achieving successful immunotherapeutic results due to their ability to regulate different T‐cell fate. ASCs also show significant adaptability to environmental stresses by modulating their immunologic profile. Cell‐based therapy for inflammatory diseases requires a detailed understanding of the molecular relation between ASCs and Th17 lymphocytes taking into account the influence of inflammation and cell ratio on such interaction. Accordingly, a dose‐dependent increase in Th17 generation was only observed in high MSC:T‐cell ratio with no significant impact of inflammatory priming. IL‐23 receptor (IL‐23R) expression by T cells was not modulated by ASCs when compared to levels in activated T cells, while ROR‐γt expression was significantly increased reaching a maximum in high (1:5) unprimed ASC:T‐cell ratio. Finally, multiplex immunoassay showed substantial changes in the secretory profile of 15 cytokines involved in the Th17 immune response (IL‐1β, IL‐4, IL‐6, IL‐10, IL‐17A, IL‐17F, IL‐22, IL‐21, IL‐23, IL‐25, IL‐31, IL‐33, IFN‐γ, sCD40, and TNF‐α), which was modulated by both cell ratio and inflammatory priming. These findings suggest that Th17 lymphocyte pathway is significantly modulated by ASCs that may lead to immunological changes. Therefore, future ASC‐based immunotherapy should take into account the complex and detailed molecular interactions that depend on several factors including inflammatory priming and cell ratio.
Identification of EPHX2 and RMI2 as two novel key genes in cervical squamous cell carcinoma by an integrated bioinformatic analysis
Authors: Liu Jinhui , Nie Sipei , Gao Mei , Jiang Yi , Wan Yicong , Ma Xiaoling , Zhou Shulin , Cheng Wenjun
Published: May 2019

Cervical cancer is the fourth most common malignancy in women worldwide and cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer. The dysregulation of genes plays a significant role in cancer. In the present study, we screened out differentially expressed genes (DEGs) of CESC in the GSE63514 data set from the Gene Expression Omnibus database. An integrated bioinformatics analysis was used to select hub genes, as well as to investigate their related prognostic signature, functional annotation, methylation mechanism, and candidate molecular drugs. As a result, a total of 1907 DEGs were identified (944 were upregulated and 963 were downregulated). In the protein–protein interaction network, three hub modules and 30 hub genes were identified. And two hub modules and 116 hub genes were screened out from four CESC‐related modules by the weighted gene coexpression network analysis. The gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. Genes with a significant prognostic value were found by prognostic signature analysis. And there were five genes (EPHX2, CHAF1B, KIAA1524, CDC45, and RMI2) identified as significant CESC‐associated genes after expression validation and survival analysis. Among them, EPHX2 and RMI2 were noted as two novel key genes for the CESC‐associated methylation and expression. In addition, four candidate small molecule drugs for CESC (camptothecin, resveratrol, vorinostat, and trichostatin A) were defined. Further studies are required to explore these significant CESC‐associated genes for their potentiality in diagnosis, prognosis, and targeted therapy.
Anti‐inflammatory roles of microRNA 21 in lipopolysaccharide‐stimulated human dental pulp cells
Authors: Nara Keisuke , Kawashima Nobuyuki , Noda Sonoko , Fujii Mayuko , Hashimoto Kentaro , Tazawa Kento , Okiji Takashi
Published: May 2019

microRNAs are small noncoding RNA molecules that regulate RNA silencing and posttranscriptional gene expression, and many microRNAs are involved in inflammatory processes. In particular, microRNA 21 (miR‐21) is upregulated in inflammatory environment and reported to induce anti‐inflammatory responses. However, the involvement of miR‐21 in pulpal inflammation and the precise mechanisms of anti‐inflammatory reactions induced by miR‐21 remain unclear. We hypothesized that miR‐21‐5p expression is induced in lipopolysaccharide (LPS)‐stimulated human dental pulp cells (hDPCs) and that miR‐21‐5p downregulates the proinflammatory cytokine expression in LPS‐stimulated hDPCs. We found that miR‐21‐5p was upregulated in LPS‐stimulated hDPCs concomitant with elevated proinflammatory cytokine expression and nuclear factor‐kappa B (NF‐κB) phosphorylation. miR‐21‐5p and cytokine expression were downregulated by BAY11‐7085 and caffeic acid phenylethyl ester (CAPE), specific and potent NF‐κB inhibitors. Enforced expression of miR‐21‐5p downregulated the Toll‐like receptor (TLR)/NF‐κB signaling via reducing the expression of TNF receptor‐associated factor 6 (TRAF6) and programmed cell death 4 (PDCD4), which further induced the decrease of proinflammatory cytokine expression. hDPCs forcibly overexpressing miR‐21‐5p downregulated the LPS‐induced expression of TNF receptor‐associated factor 6 (TRAF6; a component of the Toll‐like receptor [TLR]/NF‐κB signaling pathway), programmed cell death 4 (PDCD4, a positive regulator of the TLR/NF‐κB signaling pathway), and proinflammatory cytokines. In contrast, miR‐21‐5p inhibitor‐transfected hDPCs upregulated the expression of TRAF6, PDCD4, and inflammatory cytokines following LPS stimulation. These findings suggest that miR‐21‐5p expression was induced by the NF‐κB signaling pathway, which was in turn negatively regulated by miR‐21‐5p via downregulation of TRAF6 and PDCD4 expression in LPS‐stimulated hDPCs.
MiR‐455‐5p ameliorates HG‐induced apoptosis, oxidative stress and inflammatory via targeting SOCS3 in retinal pigment epithelial cells
Authors: Chen Pan , Miao Ying , Yan PuJun , Wang Xiao Jie , Jiang ChunXia , Lei Yi
Published: May 2019

Diabetic retinopathy (DR) remains the leading cause of blindness in adults with diabetes mellitus. Numerous microRNAs (miRNAs) have been identified to modulate the pathogenesis of DR. The main purpose of this study was to evaluate the potential roles of miR‐455‐5p in high glucose (HG)‐treated retinal pigment epithelial (RPE) cells and underlying mechanisms. Our present investigation discovered that the expression of miR‐455‐5p was apparently downregulated in ARPE‐19 cells stimulated with HG. In addition, forced expression of miR‐455‐5p markedly enhanced cell viability and restrained HG‐induced apoptosis accompanied by decreased BCL2‐associated X protein (Bax)/B‐cell leukemia/lymphoma 2 (Bcl‐2) ratio and expression of apoptotic marker cleaved caspase‐3 during HG challenged. Subsequently, augmentation of miR‐455‐5p remarkably alleviated HG‐triggered oxidative stress injury as reflected by decreased the production of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) content as well as NADPH oxidase 4 expression, concomitant with enhanced the activities of superoxide dismutase, catalase, and GPX stimulated with HG. Furthermore, enforced expression of miR‐455‐5p effectively ameliorated HG‐stimulated inflammatory response as exemplified by repressing the secretion of inflammatory cytokines interleukin 1β (IL‐1β), IL‐6, and tumour necrosis factor‐α in ARPE‐19 cells challenged by HG. Most importantly, we successfully identified suppressor of cytokine signaling 3 (SOCS3) as a direct target gene of miR‐455‐5p, and miR‐455‐5p negatively regulated the expression of SOCS3. Mechanistically, restoration of SOCS3 abrogated the beneficial effects of miR‐455‐5p on apoptosis, accumulation of ROS, and inflammatory factors production in response to HG. Taken together, these findings demonstrated that miR‐455‐5p relieved HG‐induced damage through repressing apoptosis, oxidant stress, and inflammatory response by targeting SOCS3. The study gives evidence that miR‐455‐5p may serve as a new potential therapeutic agent for DR treatment.
The Misshapen subfamily of Ste20 kinases regulate proliferation in the aging mammalian intestinal epithelium
Authors: Li Qi , Nirala Niraj K. , Chen Hsi‐Ju , Nie Yingchao , Wang Wei , Zhang Biliang , Czech Michael P. , Wang Qi , Xu Lan , Mao Junhao , Ip Y. Tony
Published: May 2019

The intestinal epithelium has a high rate of cell turn over and is an excellent system to study stem cell‐mediated tissue homeostasis. The Misshapen subfamily of the Ste20 kinases in mammals consists of misshapen like kinase 1 (MINK1), mitogen‐activated protein kinase kinase kinase kinase 4 (MAP4K4), and TRAF2 and NCK interacting kinase (TNIK). Recent reports suggest that this subfamily has a novel function equal to the Hippo/MST subfamily as upstream kinases for Warts/Large tumor suppressor kinase (LATS) to suppress tissue growth. To study the in vivo functions of Mink1, Map4k4, and Tnik, we generated a compound knockout of these three genes in the mouse intestinal epithelium. The intestinal epithelia of the mutant animals were phenotypically normal up to approximately 12 months. The older animals then exhibited mildly increased proliferation throughout the lower GI tract. We also observed that the normally spatially organized Paneth cells in the crypt base became dispersed. The expression of one of the YAP pathway target genes Sox9 was increased while other target genes including CTGF did not show a significant change. Therefore, the Misshapen and Hippo subfamilies may have highly redundant functions to regulate growth in the intestinal epithelium, as illustrated in recent tissue culture models.
Retracted: Visible‐light‐driven mitigation of antibiotic oxytetracycline and disinfection of Escherichia coli using magnetic recyclable Ag‐modified zinc ferrite/diatomite ternary hybrid material
Authors: Wu Qiong , Zhang Zhaohong
Published: May 2019

BACKGROUND

The pharmaceutical residues in water are considered globally to be typical hazardous pollutants. Many technologies have been reported to eliminate these residues, such as photocatalysis, which has usually been applied in a suspension system with powdery photocatalyst. The disadvantage of this system, hindering its practical application, is its low recyclability. Ferrite‐based photocatalysts have been synthesized to resolve this problem. In this work, silver (Ag)‐modified zinc ferrite (ZnFe2O4) nanoparticles were immobilized onto porous mineral diatomite. The physicochemical properties of this composite were studied systematically, and its photocatalytic efficiency was investigated via the degradation of antibiotic oxytetracycline (OTC) and disinfection of bacteria Escherichia coli under visible light.

RESULTS

The degradation rate increased after the catalyst was immobilized onto diatomite, due to the adsorption and degradation synergistic effect. The Ag cluster improved the visible‐light‐driven photoactivity of ZnFe2O4, and its optimal percentage was determined. The best catalyst dosage during the degradation process also was obtained. The optimal catalyst exhibited its removal rate of OTC (10 mg L−1 aqueous solution) as 90.5% in 2.5 h, and disinfection rate of E. coli as 87.2% in 2 h, under visible light irradiation. Moreover, the photocatalysis mechanism was illustrated.

CONCLUSION

This composite could be recovered simply from the water body via an external magnet, and indicated no obvious decrease of photoactivity after being recycled five times for photodegradation or photodisinfection tests. This nanocomposite showed good potential for application in wastewater remediation process, thanks to its high photocatalytic efficiency under visible light, as well as its good reusability and stability. © 2019 Society of Chemical Industry
Statistical optimization and kinetic analysis of the extraction of phenolic compounds from olive leaves
Authors: Lamprou George K , Vlysidis Anestis , Tzathas Konstantinos , Vlyssides Apostolos G
Published: May 2019

Background

Olive leaves are considered to be one of the most abundant agricultural waste source rich in phenolic compounds. A new method for extracting the phenolic compounds contained in olive leaves was developed in this study. The method was based on the addition of sulfuric acid (H2SO4), hydrolyzing the olive leaves and producing extracts rich in phenolic compounds. Experimental runs were carried out according to a central composite design (CCD) comprising the most important factors that affect the extraction process.

Results

The factors examined were extraction temperature, the addition of H2SO4 and the dilution of olive leaves with water. Maximum total phenolic content (TPC) was 86.4 mg GAE g–1 dry weight basis (db) at 31.9 °C, 6.4% H2SO4 (v/w) and 25.2 L : S (v/w). Validation runs on the optimum were very close to model predictions for TPC. Optimum oleuropein was 43.1 mg g−1 db at 40 °C, 2.0% H2SO4 (v/w) and 30 liquid : solid (v/w). Finally, the kinetics of TPC and oleuropein were studied at the optimum conditions designated by the CCD.

Conclusion

In this study, a new cost‐effective extraction process of phenolic compounds from olive leaves was examined as the developed process employs low‐value chemicals (i.e. H2SO4) in small amounts offering through its simplicity the right conditions to scale this process up in industrial applications integrated within olive mill facilities. © 2019 Society of Chemical Industry
In vitro biosynthesis of optically pure d‐(−)‐acetoin from meso‐2,3‐butanediol using 2,3‐butanediol dehydrogenase and NADH oxidase
Authors: Cui Zhenzhen , Zhao Yujiao , Mao Yufeng , Shi Ting , Lu Lingxue , Ma Hongwu , Wang Zhiwen , Chen Tao
Published: May 2019

BACKGROUND

Acetoin, especially the chiral l‐(+)‐ or d‐(−)‐enantiomer, is a high‐value industrial product that can be used as a pharmaceutical intermediate. However, the production of optically pure acetoin via conventional chemical synthesis is expensive. Classical microbial fermentations satisfy the criteria of green chemistry, but have numerous disadvantages, such as complicated process engineering, unsatisfactory titers or productivities, and difficult product separation due to the inevitable generation of by‐products and overly complex media. By contrast, enzymatic biocatalysis in cell‐free biosystems has numerous advantages in production of chemicals with high purity, whereas efficient enzymatic methods for the production of optically pure acetoin have rarely been reported.

RESULTS

An efficient coupled two‐enzyme system composed of 2,3‐butanediol dehydrogenase and H2O‐forming NADH oxidase was constructed to produce optically pure acetoin without introducing any substrate or by‐product. A 2,3‐butanediol dehydrogenase and three NADH oxidases were purified, characterized and assembled into different two‐enzyme systems. The best system, composed of LL‐NOX and CG‐BDH, was then selected according to the acetoin titer. After optimization of the reaction conditions, 94.0% of meso‐2,3‐butanediol was converted to d‐(−)‐acetoin. Finally, 399.7 mmol L−1 d‐(−)‐acetoin with an enantiomeric excess of 91.2% was produced in 6 h without any detected by‐products.

CONCLUSIONS

To our best knowledge, this is the first report on the production of optically pure d‐(−)‐acetoin from meso‐2,3‐butanediol in vitro using NADH oxidase to regenerate NAD+, as well as the best substrate conversion and acetoin titer among enzymatic biosynthesis. This work therefore provides an economical and green alternative for the in vitro production of d‐(−)‐acetoin. © 2019 Society of Chemical Industry
Two open source designs for a low‐cost operant chamber using Raspberry Pi™
Authors: Gurley Katelyn
Published: May 2019

After almost a century of use and development, operant chambers remain a significant financial investment for scientists. Small powerful single‐board computers such as the Raspberry Pi™ offer researchers a low‐cost alternative to expensive operant chambers. In this paper, we describe two new operant chambers, one using nose‐poke ports as operanda and another using a touchscreen. To validate the chamber designs, rats learned to perform both visual discrimination and delayed alternation tasks in each chamber. Designs and codes are open source and serve as a starting point for researchers to develop behavioral experiments or educational demonstrations.
Tests of an indifference rule in variable‐delay and double‐reward choice procedures with humans
Authors: McKerchar Todd L. , Mazur James E.
Published: May 2019

Four hundred and fifty participants were recruited from Amazon Mechanical Turk across 3 experiments to test the predictions of a hyperbolic discounting equation in accounting for human choices involving variable delays or multiple rewards (Mazur, 1984, 1986). In Experiment 1, participants made hypothetical choices between 2 monetary alternatives, 1 consisting of a fixed delay and another consisting of 2 delays of equal probability (i.e., a variable‐delay procedure). In Experiment 2, participants made hypothetical monetary choices between a single, immediate reward and 2 rewards, 1 immediate and 1 delayed (i.e., a double‐reward procedure). Experiment 3 also used a double‐reward procedure, but with 2 delayed rewards. Participants in all 3 experiments also completed a standard delay‐discounting task. Finally, 3 reward amounts were tested in each type of task ($100, $1000, and $5000). In the double‐reward conditions (Experiments 2 and 3), the results were in good qualitative and quantitative agreement with Mazur's model (1984, 1986). In contrast, when participants made choices involving variable delays (Experiment 1), there was relatively poor qualitative and quantitative agreement with this model. These results, along with our previous findings, suggest the structure of questions in hypothetical tasks with humans can be a strong determinant of the choice pattern.
Evaluation of an automated process for disclosure of negative noninvasive prenatal test results
Authors: Kalejta Cassidi D. , Higgins Sonja , Kershberg Hilary , Greenberg Jeff , Alvarado Monica , Cooke Kerry , Bhatt Sucheta , Bulpitt Denise , Armour Jamie , Bejjani Bassem , Ryan Shawnia , Elms Amanda
Published: May 2019

We designed and implemented a novel automated negative non‐invasive prenatal test (NIPT) result disclosure process using a proprietary, HIPAA‐compliant web‐based portal. High‐risk pregnant patients who opted for NIPT from 04/2017 to 12/2018 were given the option to receive their negative result through the automated process. Patients were required to watch a brief educational video and answer evaluative questions before downloading their result. After completing the process, patients completed a survey regarding their opinion of the efficiency and convenience of the process and their satisfaction. A total of 10,170 women registered online during the study period, and 8,965 completed the automated process (88%). Out of 8,965 women, 2,121 women responded to the survey (24%). Most (2,030 of 2,101) strongly agreed/agreed that they could easily navigate the patient portal (97%); 1,852 of 1,966 strongly agreed/agreed that disclosure was efficient and convenient (94%); 1,852 of 1,960 strongly agreed/agreed that they felt informed after watching a short educational video (94%); and 1,903 of 1,967 strongly agreed/agreed that they preferred downloading results rather than waiting for their next doctor's appointment (97%). This study demonstrates high patient satisfaction with this automated and scalable solution in a high‐volume health system. As the utilization of genetic testing increases, we predict greater need for innovative healthcare delivery models.
Evaluation of life cycle defective adenovirus mutants for production of adeno‐associated virus vectors
Authors: Krüger‐Haag Alexandra , Lehmann Caroline , Schmidt Erika , Sonntag Florian , Hörer Markus , Kochanek Stefan
Published: May 2019

Background

Adeno‐associated virus‐based vectors are efficient and safe drug candidates for different in vivo gene therapy applications. With increasing numbers of clinical studies based on AAV2 vectors that include not only rare, but also common diseases as a therapeutic target, there is an increased demand for the development of improved production technologies.

Methods

In the present study, we compared two life cycle defective adenovirus mutants as helper viruses for AAV2 vector production. They had deletions either in the gene coding for the preterminal protein (pTP) that is expressed early in the viral life cycle and is essential for genome replication or in the gene coding for the 100K protein, a protein with many functions, one of which is involved in virus assembly. AAV2 vector production efficiencies were evaluated by analyzing genome‐containing particles using a real‐time polymerase chain reaction and functional units were investigated by transduction assays.

Results

Somewhat contrary to our expectations, the ∆100K mutant virus showed only a moderate efficiency as a helper virus for AAV2 vector production, whereas the replication‐deficient ∆pTP mutant supported AAV2 production almost as efficiently as adenovirus wild‐type. We also showed that a temperature shift to 32°C together with extended incubation times improved AAV2 vector productivity.

Conclusions

The present study indicates the advantages of using a ∆pTP mutant adenovirus rather than adenovirus wild‐type as a helper virus for AAV2 production and also indicates that temperature shifts to lower temperatures may improve AAV2 vector production rates.
The shift in tuberculosis timing among people living with HIV in the course of antiretroviral therapy scale‐up in Malawi
Authors: Tweya Hannock , Feldacker Caryl , Mpunga James , Kanyerere Henry , Heller Tom , Ganesh Prakash , Nkosi Dave , Kalulu Mike , Sinkala George , Satumba Thomas , Phiri Sam
Published: May 2019

Introduction

Although the use of antiretroviral therapy (ART) reduces HIV‐associated tuberculosis (TB), patients living with HIV receiving ART remain at a higher risk of developing TB compared to those without HIV. We investigated the incidence of TB and the proportion of HIV‐associated TB cases among patients living with HIV who are receiving ART.

Methods

The study used TB registration and ART programme data collected between 2008 and 2017 from an integrated, public clinic in urban Lilongwe, Malawi. ART initiation was based on either WHO clinical staging or CD4 cell count. The CD4 thresholds for ART initiation eligibility was initially 250 cells/μL then changed to 350 cells/μL in 2011, 500 cells/μL in 2014 and to universal treatment upon diagnosis from 2016. Using TB registration data, we calculated the proportion of TB/HIV patients who were already on ART when they registered for TB treatment by year of TB registration. ART registration data were used to examine TB incidence by calendar year of ART follow‐up and by time on ART.

Results

The overall proportion of TB/patients living with HIV who started TB treatment while on ART increased from 21% in 2008 to 81% in 2017 but numbers remained relatively constant at 500 TB cases annually. The overall incidence rate of TB among patients on ART was 1.35/100 person‐years (95% CI 1.28 to 1.42). The incidence of TB by time on ART decreased from 6.4/100 person‐years in the first three months of ART to 0.4/100 person‐years after eight years on ART. TB incidence was highest in the first month on ART. The annual rate of TB among patients on ART rapidly decreased each calendar year and stabilized at 1% after 2013. Although the risk of developing TB decreased with year of ART initiation in univariable analysis, there was no significant association after adjusting for sex, age and reason for ART eligibility.

Conclusions

The decline in TB incidence over calendar years suggests protective effects of early ART initiation. The high TB incidence within the first month of ART highlights the need for more sensitive tools such as X‐ray and GeneXpert to identify patients living with HIV who have clinical and subclinical TB disease at ART initiation.
Successes and final challenges along the HIV care continuum with transwomen in San Francisco
Authors: Baguso Glenda N , Turner Caitlin M , Santos Glenn‐Milo , Raymond H Fisher , Dawson‐Rose Carol , Lin Jess , Wilson Erin C
Published: May 2019

Introduction

To examine the HIV care continuum for transwomen living in San Francisco and to determine factors associated with poor HIV‐related health outcomes.

Methods

Data were collected from 2016 to 2017 with transwomen in San Francisco. Respondent‐driven sampling (RDS) was used to recruit a population‐based sample. Bivariate associations were assessed, and RDS‐weighted multivariable logistic regression was used to identify associations between exposures and outcomes along the HIV care continuum.

Results

Of the 123 self‐identified transwomen in this analysis, ages ranged from 23 to 71 years with a majority identifying as Latina (40.8%) and African American (29.2%). An estimate of 14.3% of participants were not engaged in care, 13% were not currently on antiretroviral therapy (ART), 22.2% had a self‐reported detectable viral load and 13.5% had unknown viral load. Those using hormones had lower odds of not being on ART compared to those who did not use hormones. Those with unstable housing had a higher relative risk ratio of having a detectable viral load. Those who experienced both anti‐trans discrimination and racism had higher odds of not being in HIV care.

Conclusions

San Francisco has made substantial progress engaging transwomen in the HIV care continuum, but the final push to ensure viral suppression will require addressing social determinants. Future interventions to increase HIV care engagement, ART use and viral suppression among transwomen must address housing needs and risks related to the overlapping effect of both anti‐trans discrimination and racism.
Frontline Science: Concanavalin A-induced acute hepatitis is attenuated in vitamin D receptor knockout mice with decreased immune cell function
Authors: Umeda Naoki , Endo-Umeda Kaori , Nakashima Hiroyuki , Kato Shigeaki , Seki Shuhji , Makishima Makoto
Published: May 2019

The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D, 1α,25-dihydroxyvitamin D3, and regulates various physiologic processes, such as bone and calcium metabolism, cellular proliferation and differentiation, and immunity. VDR is highly expressed in the intestine, kidney, bone, and macrophages, but is expressed at a low level in the liver. The liver is a major metabolic organ and also acts as an immune gateway for dietary nutrients and xenobiotics. In this study, we investigated the function of VDR in hepatic immune cells, such as Kupffer cells/macrophages, utilizing VDR knockout (KO) mice. We showed that VDR is functionally expressed in hepatic mononuclear cells, specifically resident Kupffer cells. We examined the role of VDR in acute hepatitis induced by concanavalin A (Con-A) and found that Con-A-induced hepatitis is attenuated in VDR-KO mice compared to wild-type (WT) mice. Con-A-induced hepatitis is known to be mediated by NKT cell activation, cytokine production, and reactive oxygen species (ROS) production in Kupffer cells/macrophages. However, the proportions of Kupffer cells/macrophages and the NKT cell activation were similar in the liver of WT and VDR-KO mice and inflammatory cytokine gene expression was increased in VDR-KO mice. On the other hand, plasma and hepatic ROS levels were decreased in the liver of VDR-KO mice compared to WT mice. The phagocytic activity of resident Kupffer cells and hepatic neutrophils were also decreased in VDR-KO mice. Therefore, VDR is necessary for Con-A-induced acute hepatitis and plays an important role in hepatic immune cell functions.
De novo prediction of the elemental composition of peptides and proteins based on a single mass
Authors: Claesen Jürgen , Valkenborg Dirk , Burzykowski Tomasz
Published: May 2019

Identification of peptides and proteins is a common task in mass spectrometry–based proteomics but often fails to deliver a comprehensive list of identifications. Downstream analysis, quantitative or qualitative, depends on the outcome of this process. Despite continuous improvement of computational methods, a large fraction of the screened peptides and/or proteins remains unidentified.

We introduce here pacMASS, a method that de novo predicts the elemental composition of peptides and small proteins based on a single accurate mass, ie, the observed monoisotopic or average mass. This novel approach returns in a fast and memory efficient manner a limited number of elemental compositions per queried peptide or protein.