bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrite and magnetite Re–Os isotope systematics at the Laoshankou Fe–Cu–Au deposit in the northern margin of the East Junggar terrane, NW Xinjiang, China: Constraints on the multistage mineralization and metal sources
Authors: Liang Pei , Chen Huayong , Wu Chao , Xie Yuling
Published: November 2019

The northern margin of the East Junggar terrane is highly prospective for Fe–Cu–Au mineralization. However, due to the lack of precise mineralization ages, intensive debates regarding ore genesis existed. In this study, pyrite and magnetite Re–Os isotopes are first used to determine the metallogenic ages and possible genetic links with magmatism at the Laoshankou deposit, the most important Fe–Cu–Au deposit in the region.

Magnetites from Fe mineralization stage yield an 187Re/188Os versus 187Os/188Os isochron age of 391 ± 55 Ma, which is in broad agreement with ages of the Beitashan Formation volcanic rocks (~390 Ma). The low initial 187Os/188Os ratio of −0.08–0.16, depleted γOs values of −161–27 and low Re/Os(common) indicated a mantle source composition, implying Fe metals are from the Beitashan Formation Fe‐rich basalts and basaltic breccias.

Pyrites from sulfide mineralization stage yield a weighted average Re–Os model age of 390 ± 17 Ma with a matched 187Re versus 187Osr (radiogenic 187Os) isochron age of 391 ± 9 Ma, consistent with the symbiotic molybdenite Re–Os model age of 383.2 ± 4.5 Ma, indicating a timing of ~380 Ma for sulfide–Cu–Au mineralization. The high initial 187Os/188Os ratio of 0.53–3.6, large positive γOs values of 323–2,754 and higher Re/Os(common) indicated the increase of crustal materials, which is further limited to the Beitashan Formation S‐rich marine sedimentary rocks.

In summary, based on the significant two‐stage mineralization, that is, Fe (~390 Ma) and sulfide–Cu–Au (~380 Ma), and the different nonmagmatic fluid and metal sources, we prefer considering the Laoshankou Fe–Cu–Au deposit as an IOCG‐type.
Microglia and sexual differentiation of the developing brain: A focus on extrinsic factors
Authors: VanRyzin Jonathan W. , Marquardt Ashley E. , Pickett Lindsay A. , McCarthy Margaret M.
Published: November 2019

Microglia, the innate immune cells of the brain, have recently been removed from the position of mere sentinels and promoted to the role of active sculptors of developing circuits and cells. Alongside their functions in normal brain development, microglia coordinate sexual differentiation of the brain, a set of processes which vary by region and endpoint like that of microglia function itself. In this review, we highlight the ways microglia are both targets and drivers of brain sexual differentiation. We examine the factors that may drive sex differences in microglia, with a special focus on how changing microenvironments in the developing brain dictate microglia phenotypes and discuss how their diverse functions sculpt lasting sex‐specific changes in the brain. Finally, we consider how sex‐specific early life environments contribute to epigenetic programming and lasting sex differences in microglia identity.
Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder
Authors: Vetter Nora C. , Backhausen Lea L. , Buse Judith , Roessner Veit , Smolka Michael N.
Published: November 2019

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD‐only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD‐only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ—including 36 boys with ADHD‐only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD.
Linking brain structure and activation in anterior insula cortex to explain the trait empathy for pain
Authors: Li Yun , Zhang Tingting , Li Wenjuan , Zhang Junjun , Jin Zhenlan , Li Ling
Published: November 2019

The ability to perceive, understand, and react to the feelings of others' pain is referred to as empathy for pain which is composed of two components, affective‐perceptual empathy and cognitive‐evaluative empathy. Recent reviews on the neural mechanisms of empathetic pain showed the anterior insula (AI) cortex as a core circuit for empathy. However, little is known about the modulation of brain anatomy and empathic responses by trait measures of empathy (trait empathy). Thus, we investigated whether individual variation in the personality trait of empathy is associated with individual variation in the structure of specific brain regions using voxel‐based morphometry (VBM). We further investigated the relationship between the trait empathy and the activity of the same regions using state measures of empathy for pain in a trial‐by‐trial fashion in the given situation. VBM analysis indicated a small but significant negative relationship between trait empathy and gray matter volume in the bilateral AI. Functional MRI study further demonstrated that experimentally induced activity of the bilateral AI during state empathy for pain was also correlated with trait empathy. An asymmetry exists between the right and left AI between the affective and cognitive empathy. The right AI was found to be involved in the affective‐perceptual form of empathy and the left AI was active in cognitive‐evaluative forms of empathy. The interindividual differences in trait empathy may be reflected both in the state empathy and more stable brain structure difference.
Increased fracture incidence in snow and ice conditions; a model for escalation
Authors: Al‐Azzani Waheeb , Kinghorn Alison , Williams Rhodri
Published: November 2019

Several studies have shown that the incidence of fractures during periods of snow and ice increases significantly and continues to persist despite preventative measures. The studies discussed in this article suggest that these predominantly consist of “walking wounded” with significant increase in demands in specific services such as the emergency department and the trauma and orthopaedic department. Traditionally, the only formal mechanism in place for most hospitals to react to extreme events is to declare a major incident. This is a binary, all or nothing response, and it is questionable whether an increase of snow and ice‐related fractures would be justified in triggering such an extreme response. On the other end is the “do nothing” approach, which relies heavily on the professionalism, adaptability, and resilience of the staff to deal with the additional demand. The authors present a graded surge plan model for escalation in key resources, such as staff, space, and supplies in order to achieve the most efficient response ensuring good clinical outcome for patients.
Thermal diffusion and diffusion thermo effects of Eyring‐Powell nanofluid flow with gyrotactic microorganisms through the boundary layer
Authors: Eldabe Nabil T. , Rizkalla Raafat R. , Abouzeid Mohamed Y. , Ayad Vivian M.
Published: November 2019

In this article, the effects of thermal diffusion and diffusion thermo on the motion of a non‐Newtonian Eyring Powell nanofluid with gyrotactic microorganisms in the boundary layer are investigated. The system is stressed with a uniform external magnetic field. The problem is modulated mathematically by a system of a nonlinear partial differential equation, which governs the equations of motion, temperature, the concentration of solute, nanoparticles, and microorganisms. This system is converted to nonlinear ordinary differential equations by using suitable similarity transformations with the appropriate boundary conditions. These equations are solved numerically by using the Rung‐Kutta‐Merson method with a shooting technique. The velocity, temperature, concentration of solute, nanoparticles, and microorganisms are obtained as functions of the physical parameters of the problem. The effects of these parameters on these solutions are discussed numerically and illustrated graphically through figures. It is found that the velocity decreases with the increase in the non‐Newtonian parameter and the magnetic field, whereas, the velocity increases with a rise in thermophoresis and Brownian motion. Also, the temperature increases with an increase in the non‐Newtonian parameter, magnetic field, thermophoresis, and Brownian motion. These parameters play an important role and help in understanding the mechanics of complicated physiological flows.
Heat transfer inside a horizontal channel with an open trapezoidal enclosure subjected to a heat source of different lengths
Authors: Laouira Hanane , Mebarek‐Oudina Fateh , Hussein Ahmed K. , Kolsi Lioua , Merah Amine , Younis Obai
Published: November 2019

The heat transfer phenomena inside a horizontal channel with an open trapezoidal enclosure subjected to a heat source of different lengths was investigated numerically in the present work. The heat source is considered as a local heating element of varying length, which is embedded at the bottom wall of the enclosure and maintained at a constant temperature. The air flow enters the channel horizontally at a constant cold temperature and a fixed velocity. The other walls of the enclosure and the channel are kept thermally insulated. The flow is assumed laminar, incompressible, and two‐dimensional, whereas the fluid is considered Newtonian. The results are presented in the form of the contours of velocity, isotherms, and Nusselt numbers profiles for various values of the dimensionless heat source lengths (0.16 ≤ ε ≤ 1). while, both Prandtl and Reynolds numbers are kept constant at (Pr = 0.71) and (Re = 100), respectively. The results indicated that the distribution of the isotherms depends significantly on the length of the heat source. Also, it was noted that both the local and the average Nusselt numbers increase as the local heat source length increases. Moreover, the maximum temperature is located near the heat source location.
The use of amino acid‐based nutritional feeds is effective in the dietary management of pediatric eosinophilic oesophagitis
Authors: Atwal Kiranjit , Hubbard Gary P. , Venter Carina , Stratton Rebecca J.
Published: November 2019

Introduction

Eosinophilic oesophagitis (EoE) is an immune‐mediated, chronic disease characterized by eosinophilic inflammation and esophageal dysfunction. Specific food allergens including cow's milk protein, are partially causative to disease progression, and dietary management forms three main options; the elemental diet (ED), the empirical elimination diet (EED), and the targeted elimination diet (TED). The dietary choice should be individualized, however, the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an ED for pediatric EoE with multiple food allergies, failure to thrive, unresponsive disease or unable to follow a highly restricted diet. The aim of this narrative review was to explore the effectiveness of the ED (using amino acid formula [AAF]), in the management of pediatric EoE.

Methods

Literature searches were performed to identify eligible studies that described outcomes including eosinophil count, clinical symptoms, growth, and medications.

Results

Overall, 10 eligible studies were found, with n = 462 patients assigned to receive AAF from a total of n = 748 (average age 6.7 years), for a duration of 4 to 8 weeks. The use of AAF reduced eosinophil levels and demonstrated remission (defined as ≤10 eosinophils per high power field) in 75%‐100% of children with improvements, if not resolution, in clinical symptoms. AAF was more clinically effective than the use of the EED or TED, where remission rates were 75%‐81% and 40%‐69%, respectively. Few studies collected growth outcomes, however where documented these were positive for those on AAF. The long‐term impacts of each diet were not thoroughly explored.

Conclusions

The use of AAF is a clinically effective management option for pediatric EoE, and further research is required to guide long‐term management.
Prediagnosis and postdiagnosis smoking and survival following diagnosis with ovarian cancer
Authors: Wang Tianyi , Townsend Mary K. , Simmons Vani , Terry Kathryn L. , Matulonis Ursula A. , Tworoger Shelley S.
Published: November 2019

Little is known about the influence of prediagnosis and postdiagnosis smoking and smoking cessation on ovarian cancer survival. We investigated this relationship in two prospective cohort studies, the Nurses’ Health Study (NHS) and NHSII. Analyses included 1,279 women with confirmed invasive, Stage I–III epithelial ovarian cancer. We used Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ovarian cancer‐specific mortality by smoking status, adjusting for age and year of diagnosis, tumor stage, histologic subtype, body mass index and nonsteroidal anti‐inflammatory use (postdiagnosis models only). When examining prediagnosis smoking status (assessed a median of 12 months before diagnosis), risk of death was significantly increased for former smokers (HR = 1.19, 95% CI: 1.02–1.39), and suggestively for current smokers (HR = 1.21, 95% CI: 0.96–1.51) vs. never smokers. Longer smoking duration (≥20 years vs. never, HR = 1.23, 95% CI: 1.05–1.45) and higher pack‐years (≥20 pack‐years vs. never, HR = 1.28, 95% CI: 1.07–1.52) were also associated with worse outcome. With respect to postdiagnosis exposure, women who smoked ≥15 cigarettes per day after diagnosis (assessed a median of 11 months after diagnosis) had increased mortality compared to never smokers (HR = 2.34, 95% CI: 1.63–3.37). Those who continued smoking after diagnosis had 40% higher mortality (HR = 1.40, 95% CI: 1.05–1.87) compared to never smokers. Overall, our results suggest both prediagnosis and postdiagnosis smoking are associated with worse ovarian cancer outcomes.
Molecular profiles of BRCA1‐associated ovarian cancer treated by platinum‐based therapy: Analysis of primary, residual and relapsed tumors
Authors: Sokolenko Anna P. , Bizin Ilya V. , Preobrazhenskaya Elena V. , Gorodnova Tatiana V. , Ivantsov Alexander O. , Iyevleva Aglaya G. , Savonevich Elena L. , Kotiv Khristina B. , Kuligina Ekaterina Sh. , Imyanitov Evgeny N.
Published: November 2019

Our study aimed to analyze the evolution of molecular portraits of BRCA1‐driven ovarian cancer (OC) during treatment. BRCA1 loss‐of‐heterozygosity status (LOH) and exome profiles were investigated in serial OC samples from 13 patients, which included primary tumors (n = 11) obtained before neoadjuvant therapy (NACT) or at primary debulking surgery, residual post‐NACT cancer tissues (n = 13) and tumor relapses (16 samples from 13 patients). Loss of the wild‐type BRCA1 allele was detected in 11/11 (100%) primary tumors, 6/13 (46%) residual post‐NACT OC samples and 15/16 (94%) OC relapses. Full tumor triplets were available for four patients undergoing NACT; whereas primary carcinomas from these patients demonstrated BRCA1 LOH, the retention of the wild‐type allele was detected in all four post‐NACT residual tumors. These four women provided to the study 5 recurrent OC samples; 4 out of 5 tumor relapses had BRCA1 LOH thus resembling BRCA1 status observed in primary but not residual OC tissues. TP53 mutation was detected in 12 out of 13 patients and was retained across all serial samples. OC relapses tended to acquire additional intragenic mutations in genes involved in cell migration, adhesion and cell junction assembly. BRCA1‐driven OCs demonstrate the plasticity of BRCA1 status during the treatment course. NACT results in rapid selection of pre‐existing BRCA1‐proficient cells. However, BRCA1 proficiency appears to be disadvantageous in the absence of platinum exposure, as tumor relapses usually re‐acquire BRCA1 LOH during therapy holidays.
Fetal outcomes after maternal exposure to oral antifungal agents during pregnancy: A systematic review and meta‐analysis
Authors: Liu Dan , Zhang Chuan , Wu Lin , Zhang Li , Zhang Lingli
Published: November 2019

Objective

To assess the risk of adverse fetal outcomes after exposure to oral antifungal agents during pregnancy.

Search strategy

PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to October 2018.

Selection criteria

Cohort studies and case–control studies investigating fetal outcomes following maternal exposure to oral antifungal agents.

Data collection and analysis

Two reviewers independently assessed studies for inclusion, assessed risk of bias, and extracted data. Pooled estimates were calculated for the frequency of adverse fetal outcomes.

Main results

Overall, eight cohort studies and one case–control study were included. The oral antifungal agents used during pregnancy were fluconazole and itraconazole. The data indicated that oral fluconazole exposure during pregnancy might slightly increase the risk of congenital heart defects and limb defects relative to the general population; oral itraconazole during pregnancy might increase the risk of eye defects. No difference was found between oral fluconazole/itraconazole exposure and non‐exposure in the risk of other birth defects, spontaneous abortion, or stillbirth.

Conclusion

Oral fluconazole or itraconazole may not increase the risk of birth defects. Nonetheless, the risk of congenital heart defects and limb defects after fluconazole exposure and eye defects after itraconazole exposure should be cautiously investigated.
Hybrid fully convolutional networks‐based skin lesion segmentation and melanoma detection using deep feature
Authors: Jayapriya Kalyanakumar , Jacob Israel Jeena
Published: November 2019

Fully convolutional networks (FCNs) take the input of arbitrary size and produce correspondingly sized output with efficient inference and learning. The automatic diagnosis of melanoma is very essential for reducing the mortality rate by identifying the disease in earlier stages. A two‐stage framework is used for implementing the melanoma detection, segmentation of skin lesion, and identification of melanoma lesions. Two FCNs based on VGG‐16 and GoogLeNet are incorporated for improving the segmentation accuracy. A hybrid framework is used for incorporating these two FCNs. The classification is done by extracting the feature from segmented lesion by using deep residual network and a hand‐crafted feature. Classification is done by support vector machine. The performance analysis of our framework gives a promising accuracy, that is, 0.8892 for classification in ISBI 2016 dataset and 0.853 for ISIC 2017 dataset.
The good and bad of therapeutic strategies that directly target α‐synuclein
Authors: Longhena Francesca , Faustini Gaia , Brembati Viviana , Pizzi Marina , Bellucci Arianna
Published: November 2019

Synucleinopathies are neurodegenerative diseases characterized by the accumulation of either neuronal/axonal or glial insoluble proteinaceous aggregates mainly composed of α‐synuclein (α‐syn). Among them, the most common disorders are Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and some forms of familial parkinsonism. Both α‐syn fibrils and oligomers have been found to exert toxic effects on neurons or oligodendroglial cells, can activate neuroinflammatory responses, and mediate the spreading of α‐syn pathology. This poses the question of which is the most toxic α‐syn species. What is worst, α‐syn appears as a very peculiar protein, exerting multiple physiological functions in neurons, especially at synapses, but without acquiring a stable tertiary structure. Its conformation is particularly plastic, and the protein can exist in a natively unfolded state (mainly in solution), partially α‐helical folded state (when it interacts with biological membranes), or oligomeric state (tetramers or dimers with debated functional profile). The extent of α‐syn expression impinges on the resilience of neuronal cells, as multiplications of its gene locus, or overexpression, can cause neurodegeneration and onset of motor phenotype. For these reasons, one of the main challenges in the field of synucleinopathies, which still nowadays can only be managed by symptomatic therapies, has been the development of strategies aimed at reducing α‐syn levels, oligomer formation, fibrillation, or cell‐to‐cell transmission. This review resumes the therapeutic approaches that have been proposed or are under development to counteract α‐syn pathology by direct targeting of this protein and discuss their pros and cons in relation to the current state‐of‐the‐art α‐syn biology.
Identification of essential knowledge for inpatient general medicine advanced pharmacy practice experiences
Authors: Moote Rebecca , Knutsen Shannon , Lalama Jeffrey , Henderson Meagan , Hegstrom Susan , Claiborne Michele R.
Published: November 2019

Objective

With diversity in advanced pharmacy practice experience (APPE) preceptors, rotation options, and site characteristics, inpatient general medicine (IGM) APPEs provide varied experiences for students. There is a concern for continuity of essential knowledge standards across experiences. To identify essential knowledge for students to learn during an IGM APPE.

Methods

Expert pharmacists in acute care and/or student precepting in an inpatient setting participated in a three‐round modified Delphi process to build consensus. Through three rounds of survey consensus building, experts designated 143 pharmacotherapy topics as essential or non‐essential for an IGM APPE. Topics that achieved 80% or more agreement met consensus as essential. Topics that achieved less than 80% agreement by the end of the surveys were considered non‐essential.

Results

Twenty‐eight experts reached consensus on 70 (49%) topics as essential, 40 (28%) topics as non‐essential, and 33 (23%) topics as indeterminate after round one. Three additional topics suggested by the experts were included with the 33 indeterminate topics for round two considerations. At the conclusion of round three, 73 total topics met consensus as essential for IGM APPE students. Essential topics aligned with the categories of renal, cardiovascular, gastrointestinal, and neurologic disorders as well as infectious diseases. Non‐essential topic categories consisted of oncologic, dermatologic, and gynecological/obstetric disorders.

Conclusion

Identified essential knowledge, as found in this study, may serve as a guide for preceptors and afford students the opportunity of consistent experiences across varying IGM APPEs. Validation with pharmacy curriculum and postgraduate competency recommendations support many of these consensus findings. More research is needed to identify the appropriate number of topics addressed during APPE rotations and how to assess that knowledge.
Titania nanotube morphologies for osseointegration via models of in vitro osseointegrative potential and in vivo intramedullary fixation
Authors: Baker Erin A. , Vara Alexander D. , Salisbury Meagan R. , Fleischer Mackenzie M. , Baker Kevin C. , Fortin Paul T. , Roberts Richard V. , Friedrich Craig R.
Published: November 2019

As total joint replacements increase annually, new strategies to attain solid bone‐implant fixation are needed to increase implant survivorship. This study evaluated two morphologies of titania nanotubes (TiNT) in in vitro experiments and an in vivo rodent model of intramedullary fixation, to simulate joint arthroplasty conditions. TiNT surfaces were prepared via an electrochemical etching process, resulting in two different TiNT morphologies, an aligned structure with nanotubes in parallel and a trabecular bone‐like structure. in vitro data showed bone marrow cell differentiation into osteoblasts as well as osteoblastic phenotypic behavior through 21 days. In vivo, both TiNT morphologies generated greater bone formation and bone‐implant contact than control at 12 weeks, as indicated by μCT analyses and histology, respectively. TiNT groups also exhibited greater strength of fixation compared to controls, when subjected to wire pull‐out testing. TiNT may be a promising surface modification for promoting osseointegration.
Smoking is an important factor that affects peripheral blood progenitor cells yield in healthy male donors
Authors: Zhen Changqing , Fang Xiaosheng , Ding Mei , Wang Xianghua , Yuan Dai , Sui Xiaohui , Liu Xin , Zhang Lingyan , Xu Hongzhi , Li Ying , Wang Xin
Published: November 2019

Background

Smoking could reduce the CD34+ cells in peripheral blood of healthy individual. This study aimed to investigate the correlation between smoking load and the effect of peripheral blood hematopoietic progenitor cells (PBPCs) mobilization by granulocyte colony‐stimulating factor (G‐CSF) alone in healthy donors.

Methods

Retrospective analysis was performed on 145 healthy adult PBPCs donors who underwent PBPCs mobilization and collection. Smoking factors were evaluated and correlated with mobilization responses, as indicated by the collected CD34+ cells concentration.

Results

The collected CD34+ cells concentration was closely related to pre‐CD34 (P < .001) and CD34+ cells collected per volume blood processed (P < .001) which suggested that collected CD34+ cells concentration was a reliable indicator of PBPCs mobilization efficiency. The heavy smoking donors revealed significantly lower collected CD34+ cells concentration, compared to that of the nonsmoking (P < .001) and light smoking donors (P < .05). The levels of collected CD34+ cells in light smoking were also obviously lower than that in nonsmoking donors (P < .05).There were no obvious differences in the collected CD34+ cells concentration, overall processed blood volume and total collected CD34+ cells between nonsmoking and smoking cessation groups (P = .490; P = .464; P = .819).

Conclusion

Cigarette smoking is an important factor that affects the yield of PBPCs in male donors, especially when the smoking load is more than five pack‐years. Mobilization of PBMCs could be restored by smoking cessation in chronic smokers.
Retracted: The circular RNA‐NRIP1 plays oncogenic roles by targeting microRNA‐505 in the renal carcinoma cell lines
Authors: Dong Zhen , Liu Yidong , Wang Qinghai , Wang Hongyang , Ji Jianlei , Huang Tao , Khanal Aashish , Niu Haitao , Cao Yanwei
Published: November 2019

We explored the roles and regulatory mechanisms of the circular RNA (circRNA) nuclear receptor‐interacting protein 1 (NRIP1; circNRIP1) in ACHN and CAKI‐1 cells. ACHN and CAKI‐1 cells were transfected with small‐interfering‐circNRIP1 (si‐circNRIP1) and microRNA‐505 (miR‐505) inhibitor or the corresponding controls. Cell viability was detected with the Cell Counting Kit‐8. The protein expression levels of Bcl‐2, Bax, cleaved‐caspase‐3, matrix metalloproteinase (MMP)‐2, MMP‐9, adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK), protein kinase B (AKT), phosphatidylinositol 3‐kinase (PI3K), and mammalian target of rapamycin (mTOR) were individually determined via Western blot. Quantitative reverse transcription polymerase chain reaction was used to examine the expressions of circNRIP1 and miR‐505 both in tumor cells and tissues. The apoptotic rate, the colony numbers, and the migration rate were separately determined by the Annexin V‐fluorescein isothiocyanate/propidium iodide and flow cytometer, colony formation assay, and migration assay. We found that circNRIP1 was overexpressed in tumor tissue but miR‐505 was overproduced. Silencing circZNF292 induced inhibition of cell viability, colony formation, and migration, as well as the activity of AMPK and PI3K/AKT/mTOR cascades but enhancement of apoptosis. si‐circNRIP1 stimulated the upregulation of miR‐505, whose silence abolished the effects of si‐circNRIP1 on these elements mentioned above. In conclusion, the circNRIP1 played oncogenic roles in the ACHN and the CAKI‐1 cell lines by targeting miR‐505 via stimulating AMPK and PI3K/AKT/mTOR cascades.
YY1‐mediated overexpression of long noncoding RNA MCM3AP‐AS1 accelerates angiogenesis and progression in lung cancer by targeting miR‐340‐5p/KPNA4 axis
Authors: Li Xuemei , Yu Mei , Yang Caiyong
Published: November 2019

Lung cancer is famous as an aggressive malignant tumor and is the main cause of cancer‐associated mortality globally. Tumor angiogenesis is a vital part in cancer, which influences cell proliferation and metastasis. Increasing studies have claimed that long noncoding RNAs (lncRNAs) were involved in the progression of several cancers. Based on previous studies, this study focused on the role and mechanism of lncRNA MCM3AP antisense RNA 1 (MCM3AP‐AS1) in lung cancer. At first, MCM3AP‐AS1 expression was found to be elevated in lung cancer cells. Depletion of MCM3AP‐AS1 repressed cell proliferation, migration, and angiogenesis in lung cancer cells. YY1 was confirmed to mediate MCM3AP‐AS1 transcription in lung cancer cells. Moreover, the molecular mechanism investigation revealed that MCM3AP‐AS1 could sponge miR‐340‐5p and elevate KPNA4 expression. On the basis of rescue assays, we identified that the overexpression of KPNA4 partly counteracted the suppressed effect of MCM3AP‐AS1 knockdown on angiogenesis and progression in lung cancer cells. Conclusively, the YY1‐mediated overexpression of MCM3AP‐AS1 accelerated angiogenesis and progression in lung cancer by targeting miR‐340‐5p/KPNA4 axis, which highlighted the possibility of MCM3AP‐AS1 as a promising therapeutic target for lung cancer.
M‐phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl‐2 and EMT‐related signaling pathways
Authors: Wang Yizhuo , Xiao Huijie , Wang Chang , Wu Haitao , He Hua , Yao Cheng , Cui Jiuwei , Li Wei
Published: November 2019

Background

The main issue of this study is to demonstrate whether M‐phase phosphoprotein 8 (MPP8) affect gastric tumor growth and metastasis.

Methods

Retrospective study was proceeded in 280 patients' surgical specimens with different disease stages. Loss‐of‐function assays, including 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide, flow cytometry, and transwell assays were performed to evaluate the biological function of MPP8 in gastric cancer cells. Apoptosis and metastasis relative biomarkers were measured by quantitative real‐time polymerase chain reaction and Western blot analysis.

Results

Compared with normal adjacent tissues, obviously elevated MPP8 expression was found in gastric cancer tissues. Elevated MPP8 expression was associated with male sex (vs female sex), intermediate differentiation (vs poorly differentiated cancer), and later stage (vs earlier stage). Furthermore, MPP8 overexpression in tumor tissues was marginally associated with a poor prognosis, with a significant relationship between MPP8 overexpression and prognosis among patients with poorly differentiated gastric cancer. Inhibition of MPP8 in these cells significantly suppressed proliferation and colony formation, promoted apoptosis, and repressed invasion. Furthermore, silencing of MPP8 remarkably increased apoptosis‐related proteins (p53, Bax, and PARP) expression, but downregulated Bcl‐2 expression. Silencing of MPP8 also decreased the expression of metastasis pathway‐related proteins (N‐cadherin and vimentin), and as well as the levels of anti‐oncogene ZEB1, MET, and KRAS mRNA.

Conclusion

Our findings demonstrated that MPP8 might be an oncogene by positively regulating gastric cancer cell function through the p53/Bcl‐2 and epithelial to mesenchymal transition‐related signaling pathways.
Identifying prognostic biomarkers in endometrial carcinoma based on ceRNA network
Authors: Zhao Dongli , Ren Chune , Yao Yan , Wang Qinjian , Li Fei , Li Yang , Jiang Aifang , Wang Guili
Published: November 2019

Purpose

Endometrial carcinoma (EC), a common gynecological malignancy with high incidence, affects the mental and physical health of women. Mounting evidence shows that long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) have instrumental roles in various biological processes associated with the pathogenesis of EC. In this research, we intend to further study the mechanism of EC and the potential predictive markers of EC.

Methods

First, we obtained original data of EC RNA transcripts from The Cancer Genome Atlas database and performed differential analysis. Subsequently, according to the miRcode online software, relationship pairs of lncRNA‐miRNA were constructed, and miRNA‐mRNA pairs were established based on miRDB, TargetScan, and miRTarBase. Then, we constructed the competing endogenous RNA (ceRNA) network based on lncRNA‐miRNA and miRNA‐mRNA pairs. To further explain the function of the ceRNA network and explore the potential prognostic markers, functional enrichment analysis, and survival analysis were carried out.

Results

The research showed that there were 744 differential expression lncRNAs (DElncRNAs), 164 differential expression miRNAs (DEmiRNAs), and 2447 differential expression mRNAs (DEmRNAs) between EC tissues and normal tissues. Subsequently, we built 103 DEmiRNA‐DEmRNA interaction pairs and 369 DElncRNA‐DEmiRNA pairs. Then, we established the ceRNA network of EC, including 62 DElncRNAs, 26 DEmiRNAs, and 70 DEmRNAs. Moreover, 10 of 62 lncRNAs, 19 of 70 mRNAs, and 4 of 26 miRNAs that closely related to the survival of EC with P < .05 were obtained. Notably, based on this network, it was found that LINC00261‐hsa‐mir‐31 pair and LINC00261‐hsa‐mir‐211 target pairs could be used as the potential prognostic markers of EC.

Conclusion

This research recommended an available basis for the molecular mechanism of EC and prognosis prediction, which could help guide the subsequent treatments and predict the prognosis for patients with EC.
Identification of key microRNAs and hub genes in non‐small‐cell lung cancer using integrative bioinformatics and functional analyses
Authors: Song Feifeng , Xuan Zixue , Yang Xiuli , Ye Xiaolan , Pan Zongfu , Fang Qingxia
Published: November 2019

Non‐small‐cell lung cancer (NSCLC) is an extremely debilitating respiratory malignancy. However, the pathogenesis of NSCLC has not been fully clarified. The main objective of our study was to identify potential microRNAs (miRNAs) and their regulatory mechanism in NSCLC. Using a systematic review, two NSCLC‐associated miRNA data sets (GSE102286 and GSE56036) were obtained from Gene Expression Omnibus, and the differentially expressed miRNAs (DE‐miRNAs) were accessed by GEO2R. Survival analysis of candidate DE‐miRNAs was conducted using the Kaplan‐Meier plotter database. To further illustrate the roles of DE‐miRNAs in NSCLC, their potential target genes were predicted by miRNet and were annotated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) program. Moreover, the protein‐protein interaction (PPI) and miRNA‐hub gene regulatory network were established using the STRING database and Cytoscape software. The function of DE‐miRNAs in NSCLC cells was evaluated by transwell assay. Compared with normal tissues, a total of eight DE‐miRNAs was commonly changed in two data sets. The survival analysis showed that six miRNAs (miR‐21‐5p, miR‐31‐5p, miR‐708‐5p, miR‐30a‐5p, miR‐451a, and miR‐126‐3p) were significantly correlated with overall survival. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that target genes of upregulated miRNAs were enriched in pathways in cancer, microRNAs in cancer and proteoglycans in cancer, while the target genes of downregulated miRNAs were mainly associated with pathways in cancer, the PI3K‐Akt signaling pathway and HTLV‐I infection. Based on the miRNA‐hub gene network and expression analysis, PTEN, EGFR, STAT3, RHOA, VEGFA, TP53, CTNNB1, and KRAS were identified as potential target genes. Furthermore, all six miRNAs exhibited significant effects on NSCLC cell invasion. These findings indicate that six DE‐miRNAs and their target genes may play important roles in the pathogenesis of NSCLC, which will provide novel information for NSCLC treatments.
Compromising the constitutive p16INK4a expression sensitizes human neuroblastoma cells to Hsp90 inhibition and promotes premature senescence
Authors: Kanugovi Abhijnya Vijayavittal , Joseph Chitra , Siripini Satish , Paithankar Khanderao , Amere Sreedhar Subbarao
Published: November 2019

The Hsp90 chaperone has become the attractive pharmacological target to inhibit tumor cell proliferation. However, tumor cells can evolve with mechanisms to overcome Hsp90 inhibition. Using human neuroblastoma, we have investigated one such limitation. Here, we demonstrate that neuroblastoma cells overcome the interference of tumor suppressor p16INK4a in cell proliferation, which is due to its latent interaction with CDK4 and CDK6. Cells also displayed impedance to the pharmacological inhibition of cancer chaperone Hsp90 inhibition with respect to induced cytotoxicity. However, the p16INK4a knockdown has triggered the activation of cyclin‐CDK6 axis and enhanced the cell proliferation. These cells are eventually sensitized to Hsp90 inhibition by activating the DNA damage response mediated through p53‐p21WAF‐1 axis and G1 cell cycle exit. While both CDK4 and CDK6 have exhibited low affinity to p16INK4a, CDK6 has exhibited high affinity to Hsp90. Destabilizing the CDK6 interaction with Hsp90 has prolonged G2/M cell cycle arrest fostering to premature cellular senescence. The senescence driven cells exhibited compromised metastatic potential both in vitro as well as in mice xenografts. Our study unravels that cancer cells can be adapted to the constitutive expression of tumor suppressors to overcome therapeutic interventions. Our findings display potential implication of Hsp90 inhibitors to overcome such adaptations.
M2‐polarized tumor‐associated macrophages promote epithelial‐mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma
Authors: Sun Dalong , Luo Tiancheng , Dong Pingping , Zhang Ningping , Chen Jing , Zhang Shuncai , Dong Ling , Janssen Harry L. A. , Zhang Si
Published: November 2019

Tumor‐associated macrophages (TAMs) have been considered as a major component of the tumor microenvironment. However, the crosstalk between M2‐polarized tumor‐associated macrophages (M2‐TAMs) and intrahepatic cholangiocarcinoma (ICC) remains undetermined. In the present study, we aimed to clarify the role of M2‐TAMs in ICC and the underlying mechanism. The in vitro assay demonstrated M2‐TAMs promoted epithelial‐mesenchymal transition (EMT) of ICC cells, resulting in enhanced cell invasion and metastasis ability. Moreover, M2‐TAMs modulated the microenvironment of ICC by increasing the secretion of cytokines (GM‐CSF, tumor necrosis factor‐α [TNF‐α], ICAM‐1, interleukin‐6 [IL‐6], etc) and chemokines (CCL1, CCL3, etc). In addition, p‐AKT (Ser473) and p‐PRAS40 (Thr246) were upregulated in ICC cells when cocultured with M2‐TAMs or treated with M2‐TAMs secreted core cytokines (GM‐CSF, TNF‐α, ICAM‐1, and IL‐6). Consistently, AKT3 silencing (but not AKT1 silencing and AKT2 silencing) markedly inhibited phosphorylation of AKT and PRAS40 of ICC cells and inhibited the EMT process when cocultured with M2‐TAMs. Taken together, the current data indicated that M2‐TAMs promoted ICC cells EMT, partially through increasing secretion of cytokines and chemokines, thus modulating the microenvironment and activating the AKT3/PRAS40 signaling pathway.
Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer
Authors: Liu Wen‐Jing , Zhao Gang , Zhang Chen‐Yan , Yang Chang‐Qing , Zeng Xiang‐Bin , Li Jin , Zhu Kun , Zhao Shi‐Qi , Lu Hui‐Meng , Yin Da‐Chuan , Lin Sheng‐Xiang
Published: November 2019

Breast cancer (BC) and prostate cancer (PC) are the second most common malignant tumors in women and men in western countries, respectively. The risks of death are 14% for BC and 9% for PC. Abnormal estrogen and androgen levels are related to carcinogenesis of the breast and prostate. Estradiol stimulates cancer development in BC. The effect of estrogen on PC is concentration‐dependent, and estrogen can regulate androgen production, further affecting PC. Estrogen can also increase the risk of androgen‐induced PC. Androgen has dual effects on BC via different metabolic pathways, and the role of the androgen receptor (AR) in BC also depends on cell subtype and downstream target genes. Androgen and AR can stimulate both primary PC and castration‐resistant PC. Understanding the mechanisms of the effects of estrogen and androgen on BC and PC may help us to improve curative BC and PC treatment strategies.
Extracellular vesicles from oviductal isthmus and ampulla stimulate the induced acrosome reaction and signaling events associated with capacitation in bovine spermatozoa
Authors: Franchi A. , Moreno‐Irusta A. , Domínguez E. M. , Adre A. J. , Giojalas L. C.
Published: November 2019

Cells can communicate with other neighboring or distant cells through the secretion of extracellular vesicles (EV), composed of a lipid bilayer and bearing surface molecules that allow them to recognize target cells. In this way, EV induce signaling via different mechanisms, modulating the physiological state of the recipient cell. EV have been identified in both male and female reproductive fluids, however, the possible role of EV isolated from female reproductive fluids has become an emerging field only recently. It is known that ejaculated mammalian spermatozoa need to undergo physiological preparation in the female reproductive tract to fertilize the egg. EV secreted by different regions of the female tract constitute signals that may have a key role in regulating sperm functions. The aims of the present study were isolating EV from different regions of the bovine oviduct and analyzing their interaction and physiological effects on spermatozoa. Here, we report the characterization of bovine oviductal fluid EV from the isthmus and ampulla region and their effect on the induced acrosome reaction and signaling events associated with sperm capacitation. EV induced an increase in sperm protein tyrosine phosphorylation, while cell survival of cryopreserved bovine spermatozoa was maintained. We also show that EV uptake regulates the sperm calcium levels by inducing an immediate increase in the intracellular calcium concentration and sperm priming, after a pre‐incubation period, of the progesterone‐induced intracellular calcium rise. Our data contribute to understand the role of EV in the communication between the female reproductive tract and the sperm physiology, information that may be used to improve the efficiency of reproductive assisted technologies.
Molecular characterization of lung cancer: A two‐miRNA prognostic signature based on cancer stem‐like cells related genes
Authors: Cheng Yanping , Yang Sheng , Shen Bo , Zhang Yan , Zhang Xiaomei , Liu Tong , Xu Siyi , Sui Jing , Yin Lihong , Pu Yuepu , Liang Geyu
Published: November 2019

Lung cancer is one of the deadliest cancers worldwide. To increase the survival rate of lung cancer, it is necessary to explore specific prognosis markers. More and more evidence finds that noncoding RNA is closely associated with the survival of lung cancer, and cancer stem cells (CSCs) also play a significant role in the progress of lung cancer. The objective of this study is to find CSLCs genes that affect the prognosis of lung cancer. The differential expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs) in the Cancer Genome Atlas (TCGA) database and differential expression data from microarray of CD326+ and CD326− A549 cell are intersected to identify stable and consistent expression genes (2 lncRNAs, 15 miRNAs, and 134 mRNAs). The intersection of lncRNAs and miRNAs is analyzed by univariate and multivariate Cox regression to obtained prognostic genes. Two miRNAs (miR‐30b‐5p and miR‐29c‐3p) are significantly correlated with the overall survival rate. Then using these two miRNAs to construct a risk score model as a prognosis signature of lung cancer. Subsequently, we analyzed the association between two miRNAs and clinical information of lung cancer patients, of which T stage, Neoplasm cancer and risk score (P < .05) can be used as independent prognostic indicators of lung cancer. Finally, target genes of 2 miRNAs and 134 mRNAs were annotated with Gene Ontology and analyzed with Kyoto Encyclopedia of Genes and Genomes pathway, and verified with the GEO database. In summary, this study illustrates the role of miRNAs in the promotion of lung cancer by CSCs, which is important to find molecular biomarkers of lung cancer.
Genetic diversity of Paramecium species on the basis of multiple loci analysis and ITS secondary structure models
Authors: Tasneem Fareeda , Shakoori Farah R. , Ilyas Muhammad , Shahzad Naveed , Potekhin Alexey , Shakoori Abdul R.
Published: November 2019

Among ciliates, Paramecium has become a privileged model for the study of “species problem” particularly in the case of the “Paramecium aurelia complex” that has been intensely investigated. Despite extensive studies, the taxonomy of Paramecium is still challenging. The major problem is an uneven sampling of Paramecium with relatively few representatives of each species. To investigate species from the less discovered region (Pakistan), 10 isolates of Paramecium species including a standing‐alone FT8 strain previously isolated by some of us were subjected to molecular characterization. Fragments of 18S recombinant DNA (rDNA), ITS1‐5.8S‐ITS2‐5′LSU rDNA, cytochrome c oxidase subunit II, and hsp70 genes were used as molecular markers for phylogenetic analysis of particular isolates. The nucleotide sequences of polymerase chain reaction products of all markers were compared with the available sequences of relevant markers of other Paramecium species from GenBank. Phylogenetic trees based on all molecular markers showed that all the nine strains had a very close relationship with Paramecium primaurelia except for the FT8 strain. FT8 consistently showed its unique position in comparison to all other species in the phylogenetic trees. Available sequences of internal transcribed spacer 1 (ITS1) and ITS2 and some other ciliate sequences from GenBank were used for the construction of secondary models. Two highly conserved helices supported by compensatory base changes among all ciliates of ITS2 secondary structures were found similar to other eukaryotes. Therefore, the most conserved 120 to 180 base pairs regions were identified for their comparative studies. We found that out of the three helices in ITS1 structure, helix B was more conserved in Paramecium species. Despite various substitutions in the primary sequence, it was observed that secondary structures of ITS1 and ITS2 could be helpful in interpreting the phylogenetic relationships both at species as well as at generic level.