bluuebunny/crossref_metadata_2025 huggingface dataset:
Strain‐Promoted Double Azide Addition to Octadehydrodibenzo[12]annulene Derivatives
Authors: Fukushima Satomi , Ashizawa Minoru , Kawauchi Susumu , Michinobu Tsuyoshi
Published: February 2019

Octadehydrodibenzo[12]annulenes (DBAs), readily available by the oxidative acetylenic coupling of 1,2‐diethynylbenzene derivatives, were reacted with organic azides. As compared to the well‐known strain‐promoted azide‐alkyne cycloaddition (SpAAC) of 5,6,11,12‐tetradehydrodibenzo[a,e][8]annulene, the reactivity of the DBA alkynes was lower due to the lower strain energy. However, the regioselective double azide addition occurred without any side reactions under mild conditions, yielding bis‐triazole products. The structures of the products were confirmed by an X‐ray crystal structure analysis, and the reaction mechanism was studied by 1H‐NMR spectroscopy and computational studies. It was also found that the DBAs were hardly fluorescent, while the bis‐triazole products showed a green fluorescence with quantum yields up to 5.1 %. Finally, the new strain‐promoted double azide addition to the DBAs was used for step‐growth polymerization, successfully producing a high molecular weight triazole polymer.
The Influences of Global Trends in Teaching and Learning Chemistry on the Chemistry Curriculum in Israel
Authors: Mamlok‐Naaman Rachel , Taitelbaum Dorit
Published: February 2019

I this paper, we survey and focus on developments in the chemistry curriculum in Israel over the past 70 years, as influenced by changes and reforms in the curricula around the world and specifically in the United States, by political, cultural and socio‐economic factors, scientific and technological innovations, and theories and studies in learning and teaching. The mentioned studies refer also to the influence of the learners, the teachers, the content, the pedagogy of teaching and learning both in and out of school, and the assessment of students’ achievement on the curriculum changes. Three periods of changes are discussed in the chemistry curriculum in Israel, from the 1960s to the beginning of the 21st century, as influenced by the above factors.
Systematic review and meta‐analysis of randomized controlled trials of atosiban versus nifedipine for inhibition of preterm labor
Authors: Ali Aya Ashraf , Sayed Ahmed Kamal , El Sherif Loalo'a , Loutfi Gihan Ossam , Ahmed Abdullah Mahmoud Mohamed , Mohamed Hajer Bassem , Anwar Ahmad Tareq , Taha Abdullah Salah , Yahia Reem Mohamed , Elgebaly Ahmed , Abdel‐Daim Mohamed M.
Published: February 2019

Background

Two tocolytic drugs—atosiban and nifedipine—are currently used for first‐line treatment of preterm labor (PTL).

Objective

To compare the efficacy and safety of atosiban with nifedipine for PTL treatment.

Search strategy

In May 2017, we searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Clinical Trials with search terms including “nifedipine”, “atosiban”, and “preterm labor”.

Selection criteria

Randomized controlled trials of women with PTL.

Data collection and analysis

Data were extracted for study design, patient characteristics, risk of bias domains, and study outcomes. A random‐effects model was used to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs).

Results

We included seven studies that enrolled 992 patients. There was no significant difference between atosiban and nifedipine for pregnancy prolongation of 48 hours or more regarding efficacy (RR 1.06, 95% CI 0.92–1.22; P=0.440) or effectiveness (0.93, 0.84–1.03; P=0.177). Pregnancy prolongation for 7 days or more also did not differ between groups for efficacy (RR 1.04, 95% CI 0.89–1.21; P=0.656) or effectiveness (0.91, 0.79–1.05; P=0.177). Atosiban‐however‐was associated with fewer maternal side‐effects than nifedipine.

Conclusion

Atosiban resulted in fewer maternal side‐effects than nifedipine, with no difference in pregnancy prolongation.

PROSPERO registration: CRD42018090223.
Mixed‐frequency models with moving‐average components
Authors: Foroni Claudia , Marcellino Massimiliano , Stevanovic Dalibor
Published: February 2019

Temporal aggregation in general introduces a moving‐average (MA) component in the aggregated model. A similar feature emerges when not all but only a few variables are aggregated, which generates a mixed‐frequency (MF) model. The MA component is generally neglected, likely to preserve the possibility of ordinary least squares estimation, but the consequences have never been properly studied in the MF context. In this paper we show, analytically, in Monte Carlo simulations and in a forecasting application on US macroeconomic variables, the relevance of considering the MA component in MF mixed‐data sampling (MIDAS) and unrestricted MIDAS models (MIDAS–autoregressive moving average (ARMA) and UMIDAS‐ARMA). Specifically, the simulation results indicate that the short‐term forecasting performance of MIDAS‐ARMA and UMIDAS‐ARMA are better than that of, respectively, MIDAS and UMIDAS. The empirical applications on nowcasting US gross domestic product (GDP) growth, investment growth, and GDP deflator inflation confirm this ranking. Moreover, in both simulation and empirical results, MIDAS‐ARMA is better than UMIDAS‐ARMA.
ZEA exerts toxic effects on reproduction and development by mediating Dio3os in mouse endometrial stromal cells
Authors: Xie Haiqiang , Wang Huan , Li Xiaodan , Ji Haijing , Xu Yinxue
Published: February 2019

Zearalenone (ZEA) and imprinted long noncoding RNAs (lncRNAs) are both closely related to reproduction and development. However, whether they have connections in regulating reproduction and development is not clear yet. The aim of this research is to investigate their relationship. lncRNA microarray was performed to analyze differentially expressed genes, and real‐time quantitative polymerase chain reaction (PCR) was used to verify the accuracy of microarray analysis. Meanwhile, the technologies of rapid amplification of cDNA ends, RNA fluorescence in situ hybridization and bioinformatics were adopted to characterize the selected lncRNA. Analysis of lncRNA microarray showed lncRNAs and messenger RNAs related to reproduction and development were significantly differently expressed, and Dio3os was probably the target lncRNA. Then, the experiment of real‐time quantitative PCR verified the accuracy of microarray data. Characterization of Dio3os showed Dio3os, an antisense lncRNA with 2312 bp and 15 open reading frames, was enriched in the cytoplasm. Our findings suggest ZEA probably exerts toxic effects on reproduction and development by mediating Dio3os.
Differential expression patterns of specific long noncoding RNAs and competing endogenous RNA network in alopecia areata
Authors: Sheng Youyu , Ma Jingwen , Zhao Jun , Qi Sisi , Hu Ruiming , Yang Qinping
Published: February 2019

Background

Long noncoding RNAs (lncRNAs) regulate gene expression by acting with microRNAs (miRNAs) and indirectly interact with messenger RNA (mRNAs). However, the roles of specific lncRNA and its related competing endogenous RNAs (ceRNA) network in alopecia areata (AA) are not fully understood.

Methods

The blood lncRNA profiles were obtained by microarray from 10 samples, including five alopecia areata samples and five normal samples. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA‐miRNA‐mRNA network (ceRNA network) in alopecia areata.

Results

We found 154 differentially expressed lncRNAs and 46 differentially expressed genes (DEGs). The functional enrichment indicated that the DEGs mainly regulated the pathways of focal adhesion, Mucin type O‐glycan biosynthesis, and so on. The differentially expressed lncRNA (DElncRNA) involved in the pathway of thyronamine and iodothyronamine metabolism and so on. Through integrated lncRNA‐mRNA and miRNA‐mRNA pairs, the ceRNA network was constructed, thereafter, six ceRNA subnetworks were identified and subnetwork 1 were found to be significantly associated with the occurrence of alopecia areata.

Conclusion

Our results showed blood lncRNA expression patterns and a complex ceRNA network in alopecia areata. However, futher studies on blood and tissue verification of these lncRNAs and relative pathways are needed.
Antiapoptosis effect of ZiShen prescription to increase learning and memory abilities of compound Alzheimer's disease model rats
Authors: Wei Zhiqiang , Zhang Yu , Chen Yan , Xia Xiaoshuang , Zheng Boyu , Sun Xugang , Zhang Guangming , Wang Ling , Zhang Qi , Xu Chen , Jiang Shihe , Li Xiulian , Xie Bingxin , Liao Xiaohui , Ai Zhu , Li Xin
Published: February 2019

Alzheimer's disease (AD) is a neurodegenerative disease characterized progressive memory loss and cognitive impairment. In previous studies, the activities of extracts of Chinese medicinal herbs to treat brain function disorders caused by AD have already been reported. ZiShen prescription was a traditional Chinese medicine (TCM) compound prescription reformed for AD disease based on the basic theory of TCM. To explore the effect of ZiShen (kidney‐reinforcing) prescription on the learning and memory abilities, we made compound AD model rats by injecting d‐galactose and ibotenic acid into the abdominal cavity to damage both sides of the nucleus basalis of Meynert with ibotenic acid. The trisected Y‐maze was used to test the learning and memory abilities of AD model rats before and after treatment by ZiShen prescription and Piracetam. To investigate the mechanism of ZiShen prescription, the expressions of apoptosis‐related genes (Bcl‐2/Bax) in the cortex and hippocampus of compound AD model rats were detected in the cortex and hippocampus. The results show that, comparing with Piracetam, a clinical medicine to promote the thinking and memory for AD patients, ZiShen prescription significantly increased the learning and memory abilities of the compound AD model rats. After the treatment of ZiShen prescription, the expression of Bcl‐2 was upregulated, along with a downregulation of Bax in the cortex and hippocampus of compound AD model rats. And the results indicated that the clinical benefits of ZiShen prescription were slightly better than Piracetam. Still, further well‐designed studies are required to ensure the clinical effect of ZiShen.
Expression profiling analysis of long noncoding RNAs in a mouse model of ventilator‐induced lung injury indicating potential roles in inflammation
Authors: Zhang Nan‐Nan , Zhang Yi , Wang Lu , Xia Jin‐Gen , Liang Shun‐Tao , Wang Yan , Wang Zhi‐Zhi , Huang Xu , Li Min , Zeng Hui , Zhan Qing‐Yuan
Published: February 2019

The key regulators of inflammation underlying ventilator‐induced lung injury (VILI) remain poorly defined. Long noncoding RNAs (lncRNAs) have been implicated in the inflammatory response of many diseases; however, their roles in VILI remain unclear. We, therefore, performed transcriptome profiling of lncRNA and messenger RNA (mRNA) using RNA sequencing in lungs collected from mice model of VILI and control groups. Gene expression was analyzed through RNA sequencing and quantitative reverse transctiption polymerase chain reaction. A comprehensive bioinformatics analysis was used to characterize the expression profiles and relevant biological functions and for multiple comparisons among the controls and the injury models at different time points. Finally, lncRNA‐mRNA coexpression networks were constructed and dysregulated lncRNAs were analyzed functionally. The mRNA transcript profiling, coexpression network analysis, and functional analysis of altered lncRNAs indicated enrichment in the regulation of immune system/inflammation processes, response to stress, and inflammatory pathways. We identified the lncRNA Gm43181 might be related to lung damage and neutrophil activation via chemokine receptor chemokine (C‐X‐C) receptor 2. In summary, our study provides an identification of aberrant lncRNA alterations involved in inflammation upon VILI, and lncRNA‐mediated regulatory patterns may contribute to VILI inflammation.
Tracking methods and retention for a longitudinal sample of alcohol‐ and drug‐involved women on probation and parole
Authors: Northcutt Bohmert Miriam , Hoskins Kayla M. , Morash Merry
Published: February 2019

Attrition, or the progressive loss of individuals from a sample, poses a major problem in fields that carry out research to inform policy and program design. Attrition reduces statistical power by reducing sample size and compromises the external validity of findings by introducing sampling bias. If sampling bias results from disadvantages that act as barriers to research participation, then it promotes social injustice by excluding disadvantaged groups from the study. This study describes strategies used to retain participants in a longitudinal study of experiences of women under community supervision (probation or parole). It uses quantitative methods to examine sampling bias and qualitative methods to elicit accounts of participants’ explanations for being hard to reach and their recommendations for retention in future research. For participants who were and who were not retained, there were no statistically significant differences on several common quantitative predictors of retention. Hard‐to‐reach women identified residential mobility, low income, and busy lifestyles as main reasons research staff had difficulty contacting them and recommended repeated attempts at contact through multiple means. The article ends with recommendations for limiting attrition of disadvantaged, justice‐involved women in studies, and for steps to be taken when women are especially difficult to contact.
NK007 helps in mitigating paclitaxel resistance through p38MAPK activation and HK2 degradation in ovarian cancer
Authors: Li Zhenhua , Tang Xin , Luo Yu , Chen Bangyu , Zhou Congcong , Wu Xiuqing , Tang Zhenping , Qi Xiaojie , Cao Guangchao , Hao Jianlei , Liu Zonghua , Wang Qingmin , Yin Zhinan , Yang Hengwen
Published: February 2019

Ovarian cancer resistance to available medicines is a huge challenge in dire need of a solution, which makes its recurrence and mortality rate further exacerbated. A promising approach to overcome chemoresistance is drug screening from natural products. Here, we report that NK007, a (±)‐tylophorine malate isolated from the Asclepiadaceae family, selectively inhibited the proliferation of A2780 and A2780 (Taxol) cells and migration of paclitaxel‐sensitive and ‐resistant ovarian cancer cells. Interestingly, the decline of cell viability, including cell multiplication, clonality, and migration capacity was independent on cell apoptosis. At the molecular level, NK007 considerably induced G1/S arrest and upregulated the expression of phospho‐p38 mitogen‐activated protein kinase (p‐p38MAPK). In addition, hexokinase 2 (HK2) protein degradation was considerably elevated in the presence of NK007, which resulted in the reduction of oxygen consumption rate and extracellular acidification rate. Altogether, our results indicate that NK007, an analog of tylophorine, can overcome paclitaxel (PTX) resistance through p38MAPK activation and HK2 degradation. As an effective, alternative antiresistance agent, NK007 exhibits a promising potential to treat PTX‐resistant ovarian cancer.
Retracted: The role of HOTAIR‐induced downregulation of microRNA‐126 and interleukin‐13 in the development of bronchial hyperresponsiveness in neonates
Authors: Wu Dong‐Mei , Zheng Zi‐Hui , Wang Shan , Wen Xin , Han Xin‐Rui , Wang Yong‐Jian , Shen Min , Fan Shao‐Hua , Zhang Zi‐Feng , Shan Qun , Li Meng‐Qiu , Hu Bin , Zheng Yuan‐Lin , Chen Gui‐Quan , Lu Jun
Published: February 2019

Long noncoding RNAs, including HOTAIR, are involved in the pathogenesis of a wide range of diseases. This study aimed to explore the mechanism underlying the involvement of HOTAIR in neonatal bronchial hyperresponsiveness (BHR). A total of 105 newborns were recruited in this study to collect their peripheral blood mononuclear cell and serum samples, which were then divided into different genotype groups based on the genotypes of rs4759314, rs874945, and rs7958904. The real‐time polymerase chain reaction, western blot analysis, computational analyses, and luciferase assays were performed to establish the regulatory relationships between the HOTAIR, microRNA‐126 (miR‐126), and interleukin‐13 (IL‐13). The level of HOTAIR, miR‐126, and IL‐13 among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups was similar. However, the level of HOTAIR was increased in the rs7958904 GG group, accompanied by a decreased level of miR‐126 and IL‐13. In addition, the level of airway responsiveness was comparable among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups. However, the airway responsiveness in the groups rs7958904 CG and CC was much stronger than that of the GG group. We also demonstrated that, by directly binding to miR‐126, HOTAIR reduced the expression of miR‐126, which in turn decreased the expression of IL‐13. In summary, we demonstrated the role of HOTAIR‐induced downregulation of miR‐126 and IL‐13 in the development of BHR in neonates.
Preparation of novel cisplatin‐conjugated hollow gold nanospheres for targeting cervical cancer
Authors: Guan Yong‐Hong , Tian Miao , Liu Xian‐Ying , Wang Yi‐Nan
Published: February 2019

Cervical cancer is a deadly gynecological malignancy in need of innovative treatment strategies. Emerging preclinical data has suggested the benefits of nanocarriers over the traditional chemotherapy for cancer treatment. In particular, gold nanoparticles are gaining popularity due to gold's inert nature, limited side effects, good cytocompatibility, and flexibility in preparation/modification. We conjugated polyethylene glycol (PEG) with hollow gold nanospheres (HGNs) and loaded the pegylated HGNs with an anticancer drug, cisplatin to target cervical cancer. HGNs were irradiated with noninfrared laser to increase the penetration of drug into tumor tissue and improve the delivery of cisplatin. We investigated the comparative characterization studies of prepared cisplatin loaded pegylated HGNs (cis PEG‐HGNs), free cisplatin, cisplatin loaded HGNs (cis‐HGNs), cis PEG‐HGNs without laser, and cis PEG‐HGNs with laser and its effects over cervical cancer cells. Transmission electron microscopy photomicrographs confirmed the integrity of prepared HGNs. While no significant difference was observed between encapsulation efficiency and drug loading of cis‐HGNs (84.6%) and cis PEG‐HGNs (86.7%), the encapsulation efficiency increased almost twice in HGNs, compared with control gold nanoparticles (GNs) because of the hollow cavity in HGNs. In‐vitro cytotoxicity was measured by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay using HeLa cells. With irradiation, HGNs induced much elevated cytotoxicity. Not only HGNs were internalized by HeLa cells, they were retained in the cellular compartment. We also tested formulations in vivo and observed that the irradiated cis‐HGNs and cis PEG‐HGNs were most effective in regressing tumors in mice.
Retracted: Icariin attenuates methotrexate chemotherapy‐induced bone marrow microvascular damage and bone loss in rats
Authors: Hassanshahi Mohammadhossein , Su Yu‐Wen , Khabbazi Samira , Fan Chia‐Ming , Tang Qian , Wen Xuesen , Fan Jian , Chen Ke‐Ming , Xian Cory J.
Published: February 2019

Methotrexate (MTX), a widely used antimetabolite in paediatric cancer to treatment, has been widely reported to cause bone loss and bone marrow (BM) microvascular (particularly sinusoids) damage. Investigations must now investigate how MTX‐induced bone loss and microvasculature damage can be attenuated/prevented. In the present study, we examined the potency of icariin, an herbal flavonoid, in reducing bone loss and the dilation/damage of BM sinusoids in rats caused by MTX treatment. Groups of young rats were treated with five daily MTX injections (0.75 mg/kg) with and without icariin oral supplementation until Day 9 after the first MTX injection. Histological analyses showed a significant reduction in the bone volume/tissue volume (BV/TV) fraction (%) and trabecular number in the metaphysis trabecular bone of MTX‐treated rats, but no significant changes in trabecular thickness and trabecular spacing. However, the BV/TV (%) and trabecular number were found to be significantly higher in MTX + icariin‐treated rats than those of MTX alone‐treated rats. Gene expression analyses showed that icariin treatment maintained expression of osteogenesis‐related genes but suppressed the induction of adipogenesis‐related genes in bones of MTX‐treated rats. In addition, icariin treatment attenuated MTX‐induced dilation of BM sinusoids and upregulated expression of endothelial cell marker CD31 in the metaphysis bone of icariin + MTX‐treated rats. Furthermore, in vitro studies suggest that icariin treatment can potentially enhance the survival of cultured rat sinusoidal endothelial cells against cytotoxic effect of MTX and promote their migration and tube formation abilities, which is associated with enhanced production of nitric oxide.
SNX9 determines the surface levels of integrin β1 in vascular endothelial cells: Implication in poor prognosis of human colorectal cancers overexpressing SNX9
Authors: Tanigawa Kazufumi , Maekawa Masashi , Kiyoi Takeshi , Nakayama Jun , Kitazawa Riko , Kitazawa Sohei , Semba Kentaro , Taguchi Tomohiko , Akita Satoshi , Yoshida Motohira , Ishimaru Kei , Watanabe Yuji , Higashiyama Shigeki
Published: February 2019

Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High‐level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.
In vitro and in vivo studies of antiosteosarcoma activities of formononetin
Authors: Hu Wei , Wu Xianpei , Tang Jiandong , Xiao Niansu , Zhao Guoping , Zhang Li , Ou Luanhai
Published: February 2019

Osteogenic sarcoma (OGS) is a primary bone cancer, characterized by aggressive neoplasm from mesenchymal oncogenesis. However, the clinical therapeutic regimen against OGS is limited. Therefore, potential medication warrants to be further developed. Our previous study indicates that formononetin (FN) exerts effective pharmacological activity against OGS. This study aimed to further decipher the molecular mechanism behind this benefit. Patients with OGS were recruited for clinical data assay and immunoassay. Human OGS cell line (U2OS) and tumor‐bearing nude mice were subjected to a battery of biochemical analyses and immunoassays for integrative evaluation of FN‐exerted anti‐OGS effects. In human data, OGS samples showed increased expressions of ERα, p‐PI3KCATyr317, and p‐AKT
Ser473 proteins, followed by notably upregulated miR‐375 content in comparison with that in OGS‐free. In addition, FN‐treated U2OS cells showed inhibited cell proliferation, elevated lactic dehydrogenase production and lowered endogenous miR‐375 level in cells. Further, reduced immunopositive cells of Ki‐67, p‐PI3KCA
Tyr317, and p‐AKT
Ser473 were observed by the treatments of FN, while the intracellular Bax‐ and Apaf‐1‐positive cells were increased dose‐dependently. Beneficially, FN‐treated tumor‐bearing mice exhibited reduced tumor mass and intercellular miR‐375 expression. Meanwhile, immuno‐labeled cells and proteins of Bax, Caspase‐3, and Apaf‐1 in FN‐treated mice were increased dose‐dependently, whereas ERα, p‐PI3KCA
Tyr317, and p‐AKT
Ser473 positive cells and proteins were downregulated, respectively. Collectively, our current results elucidate that FN exerts effective therapeutic benefits against OGS, and the pharmacological mechanism may be related to promoting cell apoptosis by inactivating intracellular miR‐375/ERα−PI3K/AKT cascaded pathway.
Melatonin supplementation during in vitro maturation of oocyte enhances subsequent development of bovine cloned embryos
Authors: An Quanli , Peng Wei , Cheng Yuyao , Lu Zhenzhen , Zhou Chuan , Zhang Yong , Su Jianmin
Published: February 2019

Oocyte quality, which is directly related to reprogramming competence, is a major important limiting factor in animal cloning efficiency. Compared with oocytes matured in vivo, in vitro matured oocytes exhibit lower oocyte quality and reprogramming competence primarily because of their higher levels of reactive oxygen species. In this study, we investigate whether supplementing the oocyte maturation medium with melatonin, a free radical scavenger, could improve oocyte quality and reprogramming competence. We found that 10−9 M melatonin effectively alleviated oxidative stress, markedly decreased early apoptosis levels, recovered the integrity of mitochondria, ameliorated the spindle assembly and chromosome alignment in oocytes, and significantly promoted subsequent cloned embryo development in vitro. We also analyzed the effects of melatonin on epigenetic modifications in bovine oocytes. Melatonin increased the global H3K9 acetylation levels, reduced the H3K9 methylation levels, and minimally affected DNA methylation and hydroxymethylation. Genome‐wide expression analysis of genes in melatonin‐treated and nontreated oocytes was also conducted by high‐throughput RNA sequencing. Our results indicated that melatonin ameliorates oocyte oxidative stress and improves subsequent in vitro development of bovine cloned embryos.
Oroxylin A increases the sensitivity of temozolomide on glioma cells by hypoxia‐inducible factor 1α/hedgehog pathway under hypoxia
Authors: Wei Mian , Ma Rong , Huang Shaoliang , Liao Yan , Ding Youxiang , Li Zhaohe , Guo Qinglong , Tan Renxiang , Zhang Lulu , Zhao Li
Published: February 2019

Microenvironmental hypoxia‐mediated drug resistance is responsible for the failure of cancer therapy. To date, the role of the hedgehog pathway in resistance to temozolomide (TMZ) under hypoxia has not been investigated. In this study, we discovered that the increasing hypoxia‐inducible factor 1α (HIF‐1α) activated the hedgehog pathway in hypoxic microenvironment by promoting autocrine secretion of sonic hedgehog protein (Shh), and then upregulating transfer of Gli1 to the nucleus, finally contributed to TMZ resistance in glioma cells. Oroxylin A (C16H12O5), a bioactive flavonoid, could induce HIF‐1α degradation via prolyl‐hydroxylases–VHL signaling pathway, resulting in the inactivation of the hedgehog. Besides, oroxylin A increased the expression of Sufu, which is a negative regulator of Gli1. By this mechanism, oroxylin A sensitized TMZ on glioma cells. U251 intracranial transplantation model and GL261 xenograft model were used to confirm the reversal effects of oroxylin A in vivo. In conclusion, our results demonstrated that HIF‐1α/hedgehog pathway conferred TMZ resistance under hypoxia, and oroxylin A was capable of increasing the sensitivity of TMZ on glioma cells in vitro and in vivo by inhibiting HIF‐1α/hedgehog pathway and depressing the activation of Gli1 directly.
Genetic discoveries and advances in late‐onset Alzheimer’s disease
Authors: Rezazadeh Maryam , Hosseinzadeh Hassan , Moradi Mohsen , Salek Esfahani Behnaz , Talebian Shahrzad , Parvin Shaho , Gharesouran Jalal
Published: February 2019

Alzheimer’s disease (AD) is a heterogeneous disorder with multiple patterns of clinical manifestations. Recently, due to the advance of linkage studies, next‐generation sequencing and genome‐wide association studies, a large number of putative risk genes for AD have been identified using acquired genome mega data. The genetic association between three causal genes, including amyloid precursor protein, presenilin1, and presenilin2 in early‐onset AD (EOAD), was discovered over the past few decades. These discoveries showed that there should be additional genetic risk factors for both EOAD and late‐onset AD (LOAD) to help fully explain the leading molecular mechanisms in a single pathophysiological entity. This study reviews the clinical features and genetic etiology of LOAD and discusses a variety of AD‐mediated genes that are involved in cholesterol and lipid metabolism, endocytosis, and immune response according to their mutations for more efficient selection of functional candidate genes for LOAD. New mechanisms and pathways have been identified as a result.
Absence of Drug‐Drug Interaction of Anastrozole on Levonorgestrel Delivered Simultaneously by an Intravaginal Ring: Results of a Phase 2 Trial
Authors: Nave Rüdiger , Mellinger Uwe , Klein Stefan , Höchel Joachim , Schmitz Heinz
Published: February 2019

Intravaginal rings (IVRs) are an established option for continuous administration of drugs in women. The combination of anastrozole (ATZ) and levonorgestrel (LNG) in an IVR with an intended 4‐week wearing period has been considered for long‐term treatment of endometriosis‐associated pelvic pain. A randomized, parallel‐group, multicenter phase 2b study to assess the efficacy and safety of different dose combinations in women with symptomatic endometriosis has recently been performed. This paper will focus on the investigation of pharmacokinetic (PK) effects of ATZ on LNG using data collected from this study. Two hundred sixteen patients were randomized to the treatment group with IVRs releasing LNG 40 μg/day alone or in combination with ATZ 300 μg/day, 600 μg/day, or 1050 μg/day for 12 weeks. PK blood samples were taken before dosing and before IVR replacement or removal (days 28, 56, and 84). The primary PK parameter was the plasma concentration in apparent steady state of ATZ and LNG at the end of each IVR wearing period. Results of PK analysis demonstrate that ATZ concentrations increased proportionally with increasing dose (geometric mean values of 7.85, 15.48, and 22.61 μg/L at 300, 600, and 1050 μg/day nominal release, respectively). All point estimates for LNG concentration in apparent steady state ratios between the mono and combination IVR groups were close to 1, and the 90% confidence interval limits were in the 0.80 to 1.25 range (1.01 [0.85‐1.19], 1.03 [0.88‐1.20], 0.94 [0.80‐1.10]). In conclusion, our data indicate there is no evidence of drug‐drug interaction of ATZ on LNG.
Optimization of decanter temperature in separating partially miscible homoazeotrope to reduce cost and energy consumption
Authors: Li Xin , Wang Shuai , Wang Yinglong , Cui Peizhe , Xu Dongmei , Zhu Zhaoyou
Published: February 2019

BACKGROUND

There is a special type of azeotrope in the chemical industry. The components can form homoazeotrope under atmospheric pressure and azeotropic temperature but show partial miscibility when the temperature decreases. A two‐column/decanter process was presented to separate the mixture. However, the energy consumption and the total annual cost are high.

RESULTS

Based on the decanter temperature, the operating parameters of the conventional process and the modified process were optimized to achieve the minimum total annual cost (TAC). Through comparing the two processes, the minimum TAC of the latter one is 14.2% lower than that of the former one when the decanters of the two processes are at 10 °C. A control structure, which can efficiently control the modified process, was also explored and verified.

CONCLUSION

For the conventional process and the modified process, the influences of the decanter temperature on the compositions of the layered liquid phases, the total reboiler duty of the columns, and the minimum TAC demonstrated that the decanter temperature has important impacts on energy cost and economy of the two processes. Furthermore, the modified process using two cooling media in combination can further reduce the TAC. © 2019 Society of Chemical Industry
Biomolecule functionalized magnetite nanoparticles efficiently adsorb and remove heavy metals from contaminated water
Authors: Somu Prathap , Kannan Uma , Paul Subhankar
Published: February 2019

BACKGROUND

Magnetic nanoparticles (MNPs) have recently gained importance for the treatment of water contaminated with heavy metal. However, conventional chemical synthesis of MNPs involves production of hazardous by‐products. In the present study, starch (MNPST) and casein (MNPCS) functionalized MNPs were prepared via green synthesis and compared efficiency with bare MNPs.

RESULTS

Here, we prepared MNP, MNPST, and MNPCS with average sizes of 7.1, 9.0, and 9.7 nm, respectively. We conducted an adsorption study under optimized conditions such as temperature, pH, etc., and observed that the removal of lead(II) (Pb(II)) and chromium(VI) (Cr(IV)) follows the pseudo‐second‐order kinetic model for all MNPs. The experimental data fits better with Langmuir isotherm, and the maximal adsorption capacity (Qm) of MNPST was highest with 120.48 mg g−1 for Pb(II) and 99.0 mg g−1 for Cr(VI) compared to MNPCS [101.11 mg g−1 for Pb(II) and 87.81 mg g−1 for Cr(VI)] and MNP [74.07 mg g−1 for Pb(II) and 68.96 mg g−1 for Cr(VI)]. Furthermore, we also demonstrated that better regeneration capacity of MNPST was only 8.0% reduction of its removal efficiency, followed by MNPCS (12.1%) and MNP (14.8%).

CONCLUSION

Therefore, our findings revealed that starch capped magnetite nano‐adsorbent could be used for the efficient removal of heavy metal from water with excellent regeneration efficiency. © 2019 Society of Chemical Industry
Compost biochar application to contaminated soil reduces the (im)mobilization and phytoavailability of lead and copper
Authors: Chen Hongyu , Awasthi Sanjeev K , Liu Tao , Duan Yumin , Zhang Zengqiang , Awasthi Mukesh K
Published: February 2019

BACKGROUND

Biochar and compost have been proven to have significant positive effect on stabilization of toxic metals in contaminated soil. The aim of this study is to investigate the effect of compost of wheat straw biochar (CB) (4%, 8%, 12% and 18%) with different nitrogen dosages (50, 150, 250 and 300 kg ha−1) as amendment on plants growth and mobility and bioavailability of lead (Pb) and copper (Cu) as well as the nutrients in smelter‐contaminated soil.

RESULTS

Diethylenetriaminepentaacetic acid (DTPA)‐extractable and total Pb concentration were significantly (P < 0.05) decreased in the CB treated soil compared with the control, especially T14 (12% biochar applied compost with 300 kg ha−1 nitrogen) dramatically reduced the Pb content by 37.4%. While, the concentrations of total and DTPA‐Cu increased in most CB modified treatments, while, the DTPA‐Cu concentration of T11 (12% biochar applied compost with 50 kg ha−1 nitrogen) decreased by 27.3%. Meanwhile, compared with control, the CB amendment significantly improved Chinese cabbage yield and nutrients in soil.

CONCLUSIONS

Overall, the result suggested that CB could be a useful additive to decrease the bioavailability of Pb and improve plants growth and soil nutrients by reducing the ecological risk of soil contamination. © 2019 Society of Chemical Industry
Associated factors for discussing advance directives with family physicians by noncancer outpatients in Japan
Authors: Hamada Shuhei , Haruta Junji , Hamano Jun , Maeno Takami , Maeno Tetsuhiro
Published: February 2019

Background

Advance directives (ADs) are seldom discussed between primary care physicians (PCPs) and their patients, especially those with noncancer diseases. The aim was to identify the factors associated with discussing AD by noncancer patients with their physicians.

Methods

This cross‐sectional study was conducted in a hospital or clinic from October to December 2017. Physicians chose eligible noncancer patients aged 20 years or older to respond to an anonymous self‐completed questionnaire inquiring about the objective variable “I want to discuss AD with my doctor,” as well as basic characteristics, and facilitators and barriers to discussing AD identified in previous studies. The physicians responded to a survey comprising the Palliative Performance Scale (PPS) and inquiring about the disease category for each patient. Data were analyzed using binomial logistic regression analysis.

Results

A total of 270 patients (valid response rate, 79.6%) were included. Multivariate analysis identified a period of visit to the study site ≥ 3 years (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.05‐4.10), physicians who are very good at taking care of patients’ disease (OR, 12.68; 95% CI, 1.12‐143.22), and patients’ worry about their quality of life (QOL) in the future (OR, 2.69; 95% CI, 1.30‐5.57) as facilitators for discussing AD with physicians, and PPS ≤ 90 (OR, 0.51; 95% CI, 0.26‐0.98) as a barrier.

Conclusions

Our study indicates that patients’ future QOL concerns, a long period of visit to a hospital, and the presence of physical symptoms were associated with the willingness of noncancer patients to discuss AD with PCPs.
An Efficient and Facile Synthesis of tert‐Butyl 2‐(Methylamino)‐3‐nitro‐5‐oxo‐4‐aryl‐7,8‐dihydro‐4H‐pyrano[3,2‐c]pyridine‐6(5H)‐carboxylate derivatives in [BMIM]BF4
Authors: Pan Zhengbing , Xu Hui , Mao Kaimin , Dai Lei , Zhao Liming , Rong Liangce
Published: February 2019

In this research, we have developed an efficient three‐component reaction for the synthesis of pyrano[3,2‐c]pyridine derivatives from the reaction of aromatic aldehydes, tert‐butyl 2,4‐dioxopiperidine‐1‐carboxylate, and N‐methyl‐1‐(methylthio)‐2‐nitroethylen‐1‐amine in [BMIM]BF4 medium. The advantages of this method were readily available starting materials, simple reaction conditions, and satisfactory yields.
Women University Presidents: Leadership Within Bourdieu's Model of Cultural Capital
Authors: Reis Tania C. , Grady Marilyn L.
Published: February 2019

Twenty‐four of 157 U.S. public research universities, within the Carnegie Classification of Doctoral Universities: Higher and Highest Research, are led by women presidents. Using Bourdieu's model of cultural capital as a theoretical framework, eight of the women presidents were interviewed to identify their experiences negotiating a patriarchal culture of leadership. Findings of the narrative study indicated that women presidents navigate in three spheres: Becoming a Member, Leading as a Member, and Staying a Member. The findings from the narrative study show the success of women presidents, and ways they navigate within the lens of gender.
Attenuation of human herpesvirus 6B reactivation by aging
Authors: Kobayashi Nobuyuki , Nishiyama Toshiko , Yamauchi Takashi , Shimada Kazuya , Suka Machi , Kondo Kazuhiro , Yanagisawa Hiroyuki
Published: February 2019

Objective

There has been little research on human herpesvirus 6B (HHV‐6B) in healthy adults and prevalences in different age groups have been unclear. Therefore, the major objective of this study was to evaluate seroprevalence to HHV‐6 antibodies in ordinary working people and examine the effect of aging on seroprevalence. Also, as HHV‐6B is reactivated in saliva, another objective was to investigate an association between age and HHV‐6B reactivation based on measured salivary HHV‐6 DNA levels.

Methods

Our subjects were 77 ordinary office workers who underwent a health checkup. In this population, we measured anti‐HHV‐6 antibody titers using enzyme‐linked immunosorbent assay and salivary HHV‐6 DNA levels. In addition to examining an association with age, we examined associations with body mass index, smoking habit, and alcohol consumption as confounding factors.

Results

There was a significant decrease in the seropositivity of HHV‐6 antibodies in subjects of 50 years and older, and age was significantly negatively correlated with anti‐HHV‐6 antibody titers. Age and salivary HHV‐6 DNA levels were also significantly negatively correlated but there were no significant correlations with other factors.

Conclusions

Our results suggest that HHV‐6B reactivation is attenuated by aging. Thus, HHV‐6 antibodies steadily decrease in the body with aging.
Three‐dimensional analytical modeling and performance analysis of triple material trigate silicon‐on‐insulator MOSFET
Authors: Shora Aadil T. , Khanday Farooq A.
Published: February 2019

The semiconductor industry has implemented the technique of wrapping the gate electrode on different sides of channel to mitigate the degrading electrostatic effects in nanometer transistor. Intel adopted trigate architecture, wherein the channel is surrounded by gate electrode on three sides to improve the gate control over the channel. In order to further enhance the performance and diminish the short channel effects, triple material trigate silicon‐on‐insulator (SOI) MOSFET is explored in this work. An analytical model to determine the device electrostatics and match deviations due to device geometry has also been developed. The consequence of quantum confinement effects (QMEs), which arise due to ultra‐thin body structure, on the inversion charge and threshold voltage has also been included. Thus, the analytical model presented in this work is based on a self‐consistent solution of three‐dimensional Poisson's equation and two‐dimensional Schrodinger equation with proper boundary conditions. The model is verified by the uniformity obtained between the results from analytical model and TCAD simulations. The superiority of the device has been demonstrated by comparing performance parameters like potential distribution, field variations, drain induced barrier lowering (DIBL) with already existing device structures like single material trigate (SMTG) and dual material trigate (DMTG) SOI MOSFETs
Effect of interposed tissue and contamination on the initial stability of a highly porous press‐fit acetabular cup
Authors: Wiznia Daniel H. , Joyal Garrett , Schmidig Gregg , Rajaravivarma Raga , Lokesh Raja , Schwarzkopf Ran , Iorio Richard , Long William J.
Published: February 2019

For biologic fixation, press‐fit acetabular cups should have initial stability with minimal micromotion and osteoconductive surfaces in contact with bone. Inadequate exposure potentially influences initial stability by increasing the possibility of soft tissue interposition and contamination at the implant‐tissue interface. A sawbone model was used to examine how interposed tissue and contamination influence initial cup stability. Seven groups (n = 4) were tested with varying levels of interposed fatty and fibrous tissue placed around the rim of the cup. 54 millimeter in diameter highly porous hemispherical acetabular cups (Stryker, Mahwah NJ) and 54 mm reamed cavities in sawbone blocks were used. Shells were seated and maximum lever out force was recorded for each sample. Cups with fibrous tissue spaced evenly along the rim had a lever out force that was 150% of the control (107 ± 6 vs. 150 ± 12N, p = 0.005), and fatty tissue contamination had a lever out force that was 140% of the control (143 ± 18 vs. 107 ± 6N, p = 0.04). Cups with fibrous tissue placed eccentrically along the rim had a lever out force that was double the control 107 ± 6 N vs. 200 ± 15 N (p = 0.001). Surprisingly, fatty tissue contamination and fibrous tissue interposition at the rim increased initial stability. The eccentrically interposed tissue forced the opposite pole of the cup into the bone, resulting in a more secure press‐fit. However, soft tissue interposition decreases implant/bone apposition, and the effect on long term fixation is unknown. Statement of Clinical Significance: Soft tissue interposition between the bone and cup may provide higher initial stability, but its long‐term effects are unknown. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
Effects of Molecular Structure and Temperature on Micellization of Cationic Ammonium Gemini Surfactants in Aqueous Solution
Authors: Luo Siqi , Jiang Nan , Wang Yilin
Published: February 2019

Micellization of four cationic quaternary ammonium gemini surfactants, having a diethyl ether or hexyl spacer with the alkyl chain lengths of 12 and 16 carbon atoms, was studied using isothermal titration microcalorimetry (ITC) and electrical conductivity measurements in the temperature range from 298.15 to 313.15 K. In this temperature range, where surfactants are normally applied, the temperature almost does not influence the critical micelle concentration (CMC) and the degree of micelle ionization (α) values of the gemini surfactants, and the replacement of a hexyl spacer by a diethyl ether spacer leads to a slight decrease in the CMC and α values. However, as the alkyl chain length increases from 12 to 16 carbon atoms, the CMC values significantly decrease from 0.99–1.19 mM to 0.020–0.057 mM. In particular, the enthalpy of micellization (ΔHmic) and the associated thermodynamic parameters show obvious changes with varying temperature and molecular structure. ΔHmic becomes much more exothermic at higher temperature or for the surfactants with a more hydrophilic spacer. Moreover, the heat capacity change of micellization (ΔC
P, mic) is less exothermic for the surfactants with a more hydrophilic spacer or a longer alkyl chain. The enthalpy–entropy compensation data show that the surfactants with longer alkyl chains have a more stable micellar structure.
Concentration and turnover of dissolved free polyamines on the South Coast of Lake Erie
Authors: Madhuri Sumeda , Wang Kai , Bade Darren , Mou Xiaozhen
Published: February 2019

Dissolved free polyamines (DFPAs) have been suggested as an important source of reduced nitrogen in marine systems, but their importance in the cycling of dissolved organic nitrogen (DON) in freshwater systems has yet to be assessed. This study measured the concentrations, turnover and uptake rates of DFPAs and compared them with those of dissolved free amino acids (DFAAs) in samples from 21 sites along eight coastal transects on the south shore of Lake Erie (LE), a Laurentian Great Lake. DFPA compounds were consistently detected in all samples and their concentrations (16.9–191.5 nmol L−1), turnover (1.6–3.2 d−1), and uptake rates (3.2–192.0 nmol L−1 d−1) were all significantly higher than those reported in marine environments. On the other hand, corresponding DFAA measurements (45.1–822.2 nmol L−1, 3.9–11.4 d−1, and 35–1690 nmol L−1 d−1, respectively) were within the range of reported values in marine environments. The DFPA to DFAA ratios in LE samples ranged between 0.21 and 0.65, which were much higher than what have been reported in marine environments (0.01–0.07). Within the bacterioplankton community, particle‐associated (PAB) and free‐living (FLB) proportions contributed equally to the turnover of DFPAs and DFAAs in LE. PAB and FLB also contributed equally when using requested DFPAs to fulfill their carbon (BCD; 3.1–7.9%) and nitrogen (BND; 13.5–18.5%) demands. Overall, our results suggest that DFPAs is a significant component of labile DON pool in freshwater systems, where they serve more as nitrogen than carbon sources to freshwater bacterioplankton.