bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retracted: Downregulated microRNA‐135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3‐kinase/AKT signaling pathway via phosphatidylinositol 3‐kinase regulatory subunit 2
Authors: Qu Yuan , Zhang Yu‐Ping , Wu Jing , Jie Li‐Gang , Deng Jia‐Xin , Zhao Dong‐Bao , Yu Qing‐Hong 
Published: March 2019

AbstractSynovial fibroblasts (SFs) of rheumatoid arthritis (RA) are phenotypically aggressive, typically progressing into arthritic cartilage degradation. Throughout our study, we made explorations into the effects of microRNA‐135a (miR‐135a) on the SFs involved in RA by mediating the phosphatidylinositol 3‐kinase (PI3K)/AKT signaling pathway via regulation of phosphatidylinositol 3‐kinase regulatory subunit 2 (PIK3R2). The expression of PI3K was higher, the expression of PIK3R2 was lower, and AKT was phosphorylated in the RA synovial tissues, relative to the levels found in the normal synovial tissues. We predicted miR‐135a to be a candidate miR targeting PIK3R2 using an online website, microRNA.org, which was verified with a dual‐luciferase reporter gene assay. Subsequently, high miR‐135a expression was observed in RA synovial tissues. To study the effect of the interaction between miR‐135a and PIK3R2 in RA, the SFs isolated from RA samples were cultured and transfected with mimic, inhibitor, and small interfering RNA. The proliferation, invasion, and apoptosis of the SFs were detected after the transfection. The cells transfected with miR‐135a inhibitor showed inhibited cell proliferation, migration, and invasion, while also displaying promoted cell apoptosis, G0/G1 cell ratio, and decreased S cell ratio, through upregulation of PIK3R2 and inactivation of the PI3K/AKT signaling pathway. These findings provided evidence that downregulation of miR‐135a inhibits proliferation, migration, and invasion and promotes apoptosis of SFs in RA by upregulating the PIK3R2 coupled with inactivating the PI3K/AKT signaling pathway. The downregulation of miR‐135a might be a potential target in the treatment of RA.
Prolonged elevated levels of c‐kit+ progenitor cells after a myocardial infarction by beta 2 adrenergic receptor priming
Authors: Finan Amanda , Demion Marie , Sicard Pierre , Guisiano Morgane , Bideaux Patrice , Monceaux Kevin , Thireau Jérôme , Richard Sylvain 
Published: March 2019

AbstractEndogenous progenitor cells may participate in cardiac repair after a myocardial infarction (MI). The beta 2 adrenergic receptor (ß2‐AR) pathway induces proliferation of c‐kit+ cardiac progenitor cells (CPC) in vitro. We investigated if ß2‐AR pharmacological stimulation could ameliorate endogenous CPC‐mediated regeneration after a MI. C‐kit+ CPC ß1‐AR and ß2‐AR expression was evaluated in vivo and in vitro. A significant increase in the percentage of CPCs expressing ß1‐AR and ß2‐AR was measured 7 days post‐MI. Accordingly, 24 hrs of low serum and hypoxia in vitro significantly increased CPC ß2‐AR expression. Cell viability and differentiation assays validated a functional role of CPC ß2‐AR. The effect of pharmacological activation of ß2‐AR was studied in C57 mice using fenoterol administered in the drinking water 1 week before MI or sham surgery or at the time of the surgery. MI induced a significant increase in the percentage of c‐kit+ progenitor cells at 7 days, whereas pretreatment with fenoterol prolonged this response resulting in a significant elevated number of CPC up to 21 days post‐MI. This increased number of CPC correlated with a decrease in infarct size. The immunofluorescence analysis of the heart tissue for proliferation, apoptosis, macrophage infiltration, cardiomyocytes surface area, and vessel density showed significant changes on the basis of surgery but no benefit due to fenoterol treatment. Cardiac function was not ameliorated by fenoterol administration when evaluated by echocardiography. Our results suggest that ß2‐AR stimulation may improve the cardiac repair process by supporting an endogenous progenitor cell response but is not sufficient to improve the cardiac function.
Activation of α7‐nAChRs protects SH‐SY5Y cells from 1‐methyl‐4‐phenylpyridinium‐induced apoptotic cell death via ERK/p53 signaling pathway
Authors: Xu Shi , Yang Beibei , Tao Tingting , Zhang Ji , Liu Yun , Hu Jun , Fan Yi , Zhang Guangdong 
Published: March 2019

AbstractEpidemiologic studies have shown a reduced risk of developing Parkinson's disease (PD) among cigarette smokers. Nicotine, as a key component in tobacco products, is thought as a possible candidate for action of smoking in neuroprotection. α7 nicotinic acetylcholine receptors (α7‐nAChRs) is one of the most abundant nAChRs in the mammalian brain. Although nicotine is thought to exert this protective action by acting on nicotinic receptors, including the α7‐nAChRs; the mechanisms underlying how α7‐nAChRs protect against dopaminergic neuron loss are highly complex. Using nicotine and a selective α7‐nAChR agonist PNU‐282987, we first confirmed that their addition to SH‐SY5Y cells challenged with 1‐methyl‐4‐phenylpyridinium (MPP+) could afford neuroprotection and result in a reduction in apoptotic cell death. Then, we found that the pretreatment with nicotine and PNU‐282987 showed the neuroprotective antiapoptotic effects via activating the α7‐nAChRs/MAPK/p53 axis. Furthermore, we used RNA interference to silence the expression of α7‐nAChRs in SH‐SY5Y cells and found that suppressing α7‐nAChR expression diminished the antiapoptotic effects of nicotine and PNU‐282987, not the toxic effects of MPP+. Moreover, α7‐nAChR knockdown could only decrease the inhibitory effects of nicotine and PNU‐282987 on the phosphorylated extracellular signal‐regulated kinase (ERK), not c‐Jun amino‐terminal kinase and p38. Therefore, our findings indicate the important roles of ERK/MAPK signaling in the neuroprotective effects of α7‐nAChRs and suggest that α7‐nAChR agonists may be validated as novel treatments for PD.
Loss of PKC mu function induces cytoskeletal defects in mouse oocyte meiosis
Authors: Zhang Yu , Wu Lan‐Lan , Wan Xiang , Wang Hong‐Hui , Li Xiao‐Han , Pan Zhen‐Nan , Sun Shao‐Chen 
Published: March 2019

AbstractCytoskeleton which includes microtubule and actin filaments plays important roles during mammalian oocyte maturation. In the present study, we showed that protein kinase C mu (PKC mu) was one potential key molecule which affected cytoskeleton dynamics in mouse oocytes. Our results showed that PKC mu expressed and localized at the poles of the spindle during oocyte maturation, and PKC mu expression reduced in the oocytes from 6‐month‐old mice or 24 hr in vitro culture. We knocked down the expression of PKC mu in oocytes using morpholino injection to explore the relationship between PKC mu and subcellular structure defects. The loss of PKC mu reduced oocyte maturation competence, showing with decreased polar body extrusion rate and increased rate of symmetric division. Further analysis indicated that PKC mu decrease caused the spindle organization defects, and this could be confirmed by the decreased tubulin acetylation level. Moreover, we found that PKC mu affected the phosphorylation level of cofilin for actin assembly, which further affected cytoplasmic actin distribution and spindle positioning. In summary, our data indicated that PKC mu is one key factor for oocyte maturation through its roles on the spindle organization and actin filament distribution.
Activation of β‐catenin in Col2‐expressing chondrocytes leads to osteoarthritis‐like defects in hip joint
Authors: Xia Chenjie , Wang Pinger , Fang Liang , Ge Qinwen , Zou Zhen , Dong Rui , Zhang Peng , Shi Zhenyu , Xu Rui , Zhang Lei , Luo Chen , Ying Jun , Xiao Luwei , Shen Jie , Chen Di , Tong Peijian , Jin Hongting 
Published: March 2019

AbstractAlthough osteoarthritis (OA) in the hip joint is a common and debilitating degenerative disease, the precise molecular mechanisms underlying its pathological process remains unclear. This study sets out to investigate whether β‐catenin plays a critical role in hip OA pathogenesis. Here, we showed overexpressed β‐catenin protein in human OA cartilage tissues. Then, we analyzed β‐cat(ex3)Col2ER mice, in which β‐catenin gene was conditionally activated in femoral head chondrocytes. At 2 months of age, β‐cat(ex3)Col2ER mice already showed a phenotype of severe cartilage degeneration in the femoral head. More changes observed in β‐cat(ex3)Col2ER mice with age included subchondral sclerosis and osteophyte formation along joint margins, resembling a hip OA phenotype in humans. In addition, cartilage degradation and chondrocyte apoptosis as the results of β‐catenin activation possibly contributed to this hip OA‐like phenotype. Overall our findings provide direct evidence about the importance of β‐catenin in hip OA pathogenesis.
Using a variant of coverslip hypoxia to visualize tumor cell alterations at increasing distances from an oxygen source
Authors: Arocena Miguel , Landeira Mercedes , Di Paolo Andrés , Silva Alejandro , Sotelo‐Silveira José , Fernández Ariel , Alonso Julia 
Published: March 2019

AbstractEarly stages in tumor development involve growth in confined spaces, where oxygen diffusion is limited and metabolic waste products accumulate. This hostile microenvironment imposes strong selective pressures on tumor cells, leading eventually to the survival and expansion of aggressive subclones that condition further tumor evolution. To model features of this microenvironment in vitro, a diffusional barrier can be introduced in the form of a coverslip placed on top of cells, a method termed coverslip hypoxia. Using a variant of this method, with larger volume between coverslip and cells and with oxygen diffusion occurring only through a small hole in the center of the coverslip, we have visualized alterations in LNCaP tumor cells as a function of their distance to the oxygen source at the center. We observed remarkable morphological changes in LNCaP cells as the distance from the center increases, with cells becoming highly spread, displaying dynamic membrane protrusions and occasionally adopting a migratory phenotype. Concomitantly, cells farther from the center displayed marked increases in the hypoxia marker hypoxyprobe, whereas extracellular pH decreased in the same direction. Cells with altered morphology displayed prominent increases in fibrillar actin, as well as swollen mitochondria with distorted cristae and accumulation of neutral lipid‐containing intracellular vesicles. These results show that an in vitro microenvironment that models diffusional barriers encountered by tumors in situ can have profound effects on tumor cells. The coverslip hypoxia variant we describe can be used to characterize in vitro the response of tumor cells to environmental conditions that play crucial roles in early tumor development.
Long noncoding RNA SBF2‐AS1 promotes colorectal cancer proliferation and invasion by inhibiting miR‐619‐5p activity and facilitating HDAC3 expression
Authors: Chen Gang , Gu Yue , Han Peng , Li Zhong , Zhao Jin‐Lu , Gao Mei‐Zhuo 
Published: March 2019

AbstractEvidence, demonstrating long noncoding RNAs (lncRNAs) as critical players in cancer, remains to increase. lncRNA SBF2‐AS1 was reported to be involved in several cancers, such as hepatocellular carcinoma. However, the role of SBF2‐AS1 in colorectal cancer (CRC) is unknown. We showed lncRNA SBF2‐AS1 expression was growing in CRC samples, especially in advanced cases. Accordingly, SBF2‐AS1 possesses higher expression in CRC cell lines than in normal cell line. Moreover, SBF2‐AS1 high expression indicated a low survival rate. Functionally, SBF2‐AS1 knockdown suppressed the proliferation, migration, and invasion of CRC cells. In terms of mechanism, SBF2‐AS1 upregulation restrained the activity of miR‐619‐5p and led to overexpression of HDAC3. Importantly, downregulation of miR‐619‐5p or HDAC3 overexpression reversed SBF2‐AS1‐silencing‐caused suppression on proliferation and metastasis. Summarily, our findings elucidated a crucial role of SBF2‐AS1 as a miR‐619‐5p sponge, shedding novel light on lncRNA‐related prognostics.
Modelling supply chain adaptation for disruptions: An empirically grounded complex adaptive systems approach
Authors: Zhao Kang , Zuo Zhiya , Blackhurst Jennifer V. 
Published: March 2019

AbstractThrough the development and usage of an agent‐based model, this article investigates firms' adaptive strategies against disruptions in a supply chain network. Viewing supply chain networks as complex adaptive systems, we first construct and analyze a real‐world supply chain network among 2,971 firms spanning 90 industry sectors. We then develop an agent‐based simulation to show how the model of firms' adaptive behaviors can leverage competition relationships within a supply chain network. The simulation also models how disruptions propagate in the supply chain network through cascading failures. With the simulation, we seek to understand if a firm's adaptive behaviors can reduce the impact of disruptions in supply chain networks. Therefore, we propose, evaluate, and analyze two types of adaptive strategies a firm can leverage to reduce the negative effects of supply chain network disruptions. First, we deploy in our model a reactive strategy, which restructures the network in response to a disruption event among first‐tier suppliers. Next, we develop and propose proactive strategies, which are used when a distant disruption is observed but has not yet hit the focal firm. We discuss the implications related to how and when firms can improve their resilience against supply disruptions by leveraging adaptive strategies.
Revisiting the complex adaptive systems paradigm: Leading perspectives for researching operations and supply chain management issues
Authors: Nair Anand , Reed‐Tsochas Felix 
Published: March 2019

AbstractThis paper presents a conceptual model for a renewed consideration of the complex adaptive systems (CAS) perspective in operations and supply chain management research. A literature review identifies the approaches taken in published research to examine issues such as complexity, adaptation, and emergent behavior. We present a revised conceptual framework that offers directions for embracing key tenets from CAS research so as to gain deeper insights into pertinent issues within the field. We introduce the articles that are part of this special issue and highlight how these articles relate to the conceptual framework proposed in the paper. We also propose some methodological directions that can help in undertaking rigorous investigations of some important aspects that have theoretical and managerial significance.
The Association Between Negative Trauma‐Related Cognitions and Pain‐Related Functional Status Among Veterans With Posttraumatic Stress Disorder and Alcohol Use Disorder
Authors: Curry Inga , Malaktaris Anne L. , Lyons Robert , Herbert Matthew S. , Norman Sonya B. 
Published: March 2019

AbstractAmong veterans with posttraumatic stress disorder (PTSD), alcohol use disorders (AUDs) are highly prevalent. Furthermore, PTSD frequently co‐occurs with chronic pain (CP), and CP is associated with an increased risk of AUD. Pain‐related beliefs and appraisals are significantly associated with poorer pain‐related functional status, yet few studies have examined negative trauma‐related cognitions and their impact on pain‐related functional disability in veterans with co‐occurring PTSD and AUD. Accordingly, we examined the association between negative trauma‐related cognitions and pain severity and pain disability in 137 veterans seeking treatment for PTSD and AUD. Using hierarchical multiple linear regression, we found that higher levels of negative trauma‐related cognitions (e.g., “I am completely incompetent”) were associated with a higher level of pain severity, after controlling for PTSD symptom severity and frequency of alcohol use, total R2 = .07, ΔR2 = .06. Additionally, as hypothesized, we found that higher levels of negative trauma‐related cognitions were associated with higher levels of pain disability, after controlling for PTSD symptom severity, frequency of alcohol use, and pain severity, total R2 = .46, ΔR2 = .03. Given that negative trauma‐related cognitions contributed to pain severity and pain disability, even when controlling for PTSD severity and frequency of alcohol use, future studies should explore the potential impact of interventions that address negative trauma‐related cognitions (e.g., prolonged exposure or cognitive processing therapy) on pain severity and disability.
Observations at backyard bird feeders influence the emotions and actions of people that feed birds
Authors: Dayer Ashley A. , Rosenblatt Connor , Bonter David N. , Faulkner Holly , Hall Richard J. , Hochachka Wesley M. , Phillips Tina B. , Hawley Dana M. 
Published: March 2019

Abstract

Backyard bird feeding is one of the most common ways people engage with wildlife in many parts of the world. Given its scale, it can have profound consequences for the ecology of feeder birds and their behaviour. While previous work has primarily explored socio‐demographic factors associated with bird feeding, how observations of nature at backyard feeders (e.g. changes in feeder bird abundance, interaction with natural enemies and weather) influence people's propensity to feed birds remain largely unknown.

We examined the association between peoples’ observations at their backyard feeders and their emotions and behaviours related to providing food to birds. We conducted an online survey of a subset of United States participants in Project FeederWatch, a large‐scale citizen science project.

Overwhelmingly, respondents (n = 1,176) reported taking actions, such as managing predators or maintaining feeders, in response to observable natural factors (e.g. increased incidence of disease, the presence of predators, increased bird abundance). Additionally, respondents described a variety of emotional responses to the scenarios of depredation or disease at their feeders, some of which (particularly anger) had a small association with whether a respondent would take action in response. Respondents generally believed that their bird feeding benefits backyard birds (e.g. by improving overwinter survival and overall health), and indicated that natural factors (e.g. bird abundance, disease prevalence) and abiotic factors (i.e. cold temperature) had more of an influence on how much they feed birds than internal constraints such as time and money.

These findings suggest that human behaviour with respect to bird feeding is coupled to observations of nature, which could lead to feedbacks between provisioning intensity and ecological dynamics. Overall, our results have important implications for bird conservation and for understanding the potential benefits that humans receive from provisioning birds.

A plain language summary is available for this article.
Gadolinium Metallofullerene‐Based Activatable Contrast Agent for Tumor Signal Amplification and Monitoring of Drug Release
Authors: Wang Sheng , Zhou Zijian , Wang Zhantong , Liu Yijing , Jacobson Orit , Shen Zheyu , Fu Xiao , Chen Zhi‐Yi , Chen Xiaoyuan 
Published: March 2019

AbstractActivatable imaging probes are promising to achieve increased signal‐to‐noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion‐associated potential long‐term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH‐responsive polymer and gadolinium metallofullerene (GMF). This GMF‐based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH‐responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic‐to‐hydrophilic conversion of the pH‐responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.
Forecast optimal fluoride concentration data in drinking water according to the ambient temperature in Golestan, Iran
Authors: Zazouli Mohammad Ali , Kalankesh Laleh R. , Hasanpour Maryam 
Published: March 2019

AbstractControlling fluoride concentrations in drinking water at optimal levels could be effective in preventing certain negative health effects in humans. This study investigated optimal fluoride concentrations in potable water in Golestan province, according the ambient temperatures in the province. The study used data on fluoride concentrations in drinking water supplied by the Water and Wastewater Company of Golestan Province. The annual mean maximum temperatures were extracted from a website that recorded daily ambient temperature. The optimal value of fluoride in drinking water for each county of Golestan province was calculated by the Galgan and Vermillion formula. The results show that all of the counties should contain fluoride concentrations ranging from 0.73 to 0.766 milligrams per liter (mg/L) according to the calculation formula, while fluoride concentrations were instead reported to range between 0.23 and 0.53 mg/L by the Water and Wastewater company. In addition, according to World Health Organization (WHO) recommendations, the concentrations of fluoride in potable in all of the cities in Golestan province fall below the WHO standard. In conclusion, we suggest that the fluoride concentrations in Golestan province's drinking water should be taken into account by the appropriate authorities and that optimal fluoride concentrations in drinking water according to ambient temperatures be set to avoiding negative health impacts.
Rotating black holes in the FI-gauged N = 2, D = 4 $$ {\overline{\mathbb{C}\mathrm{P}}}^{\mathrm{n}} $$ model
Authors: Daniele Nicoletta , Faedo Federico , Klemm Dietmar , Ramírez Pedro F. 
Published: March 2019

AbstractWe construct supersymmetric black holes with rotation or NUT charge for the$$ {\overline{\mathbb{C}\mathrm{P}}}^n $$ℂP¯n— and the t3model ofN= 2,D= 4 U(1) FI-gauged supergravity. The solutions preserve 2 real supercharges, which are doubled for their near-horizon geometry. For the$$ {\overline{\mathbb{C}\mathrm{P}}}^n $$ℂP¯nmodel we also present a generalization to the nonextremal case, which turns out to be characterized by a Carter-Plebański-type metric, and hasn+ 3 independent parameters, corresponding to mass, angular momentum as well asn+ 1 magnetic charges. We discuss the thermodynamics of these solutions, obtain a Christodoulou-Ruffini mass formula, and shew that they obey a first law of thermodynamics and that the product of horizon areas depends on the angular momentum and the magnetic charges only. At least some of the BPS black holes that we obtain may become instrumental for future microscopic entropy computations involving a supersymmetric index.