bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Cretaceous potassic volcanic rocks from the northern margin of the Sulu orogenic belt, Shandong Province, eastern China: Constraints on petrogenesis and crust–mantle interaction
Authors: Cao Guang‐Yue , Xue Huai‐Min , Liu Zhe
Published: February 2019

A major and trace element, Sr–Nd–Hf isotope, and zircon U–Pb geochronology study was conducted on Early Cretaceous volcanic rocks from the northern margin of the Sulu orogenic belt in Shandong Province, eastern China. These results constrain the petrogenesis of the volcanic rocks and provide important insights into the significance of crust–mantle interaction. The rocks comprise high‐K basaltic andesite, shoshonites, latites, high‐K dacites, and high‐K rhyolites. U–Pb zircon dating of four representative samples of latite, two high‐K dacites, and high‐K rhyolite indicates that these rocks formed from 126 to 122 Ma. The volcanic rocks are characterized by high K2O (2.04–6.70 wt.%) and total alkalis (Na2O + K2O; 5.3–10.9 wt.%) that plot within the field for shoshonitic rocks. All the rocks are enriched in light rare earth and large‐ion lithophile elements (e.g., Rb, Th, U, and K) and are depleted in high‐field‐strength elements (e.g., Nb, Ta, and Ti). The rocks have high initial 87Sr/86Sr ratios (0.706760–0.708898), low εNd(t) values (−19.5 to −12.5), and negative εHf(t) values (−31.3 to −19.7), similar to the Early Cretaceous Jiaodong mafic dikes and intermediate–mafic volcanic rocks. These geochemical and isotopic characteristics indicate that the volcanic rocks formed through simultaneous fractional crystallization and crustal assimilation of a basaltic magma derived from metasomatized mantle. The metasomatized mantle source might have been produced by the recycling of subducted Yangtze Craton crust into the ancient lithospheric mantle of the North China Craton.
White matter tracts lesions and decline of verbal fluency after deep brain stimulation in Parkinson's disease
Authors: Costentin Guillaume , Derrey Stéphane , Gérardin Emmanuel , Cruypeninck Yohann , Pressat‐Laffouilhere Thibaut , Anouar Youssef , Wallon David , Le Goff Floriane , Welter Marie‐Laure , Maltête David
Published: February 2019

Decline of verbal fluency (VF) performance is one of the most systematically reported neuropsychological adverse effects after subthalamic nucleus deep brain stimulation (STN‐DBS). It has been suggested that this worsening of VF may be related to a microlesion due to the electrode trajectories. We describe the disruption of surrounding white matter tracts following electrode implantation in Parkinson's disease (PD) patients with STN‐DBS and assess whether damage of fiber pathways is associated with VF impairment after surgery. We retrospectively analyzed 48 PD patients undergoing bilateral STN DBS. The lesion mask along the electrode trajectory transformed into the MNI 152 coordinate system, was compared with white matter tract atlas in Tractotron software, which provides a probability and proportion of fibers disconnection. Combining tract‐ and atlas‐based analysis reveals that the trajectory of the electrodes intersected successively with the frontal aslant tract, anterior segment of arcuate tract, the long segment of arcuate tract, the inferior longitudinal fasciculus, the superior longitudinal fasciculus, the anterior thalamic radiation, and the fronto striatal tract. We found no association between the proportion fiber disconnection and the severity of VF impairment 6 months after surgery. Our findings demonstrated that microstructural injury associated with electrode trajectories involved white matter bundles implicated in VF networks.
Predicting Postoperative Liver Dysfunction Based on Blood‐Derived MicroRNA Signatures
Authors: Starlinger Patrick , Hackl Hubert , Pereyra David , Skalicky Susanna , Geiger Elisabeth , Finsterbusch Michaela , Tamandl Dietmar , Brostjan Christine , Grünberger Thomas , Hackl Matthias , Assinger Alice
Published: February 2019

There is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery and thereby determine the optimal time point of liver resection, specifically as current markers are often expensive, time consuming, and invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic, and treatment‐response biomarkers for several diseases. Using next‐generation sequencing as an unbiased systematic approach, 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative liver dysfunction (LD) after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature—consisting of miRNAs 151a‐5p, 192‐5p, and 122‐5p—that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real‐time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a‐5p to 192‐5p and 122‐5p to 151a‐5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stays, and even mortality before an operation with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Our data demonstrate the clinical utility of an miRNA‐based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in individualized patient treatment. Thereby, our data might help to tailor surgical strategies to the specific risk profile of patients.
Image‐guided cranial irradiation‐induced ablation of dentate gyrus neurogenesis impairs extinction of recent morphine reward memories
Authors: Rivera Phillip D. , Simmons Steven J. , Reynolds Ryan P. , Just Alanna L. , Birnbaum Shari G. , Eisch Amelia J.
Published: February 2019

Dentate gyrus adult neurogenesis is implicated in the formation of hippocampal‐dependent contextual associations. However, the role of adult neurogenesis during reward‐based context‐dependent paradigms—such as conditioned place preference (CPP)—is understudied. Therefore, we used image‐guided, hippocampal‐targeted X‐ray irradiation (IG‐IR) and morphine CPP to explore whether dentate gyrus adult neurogenesis plays a role in reward memories created in adult C57BL/6J male mice. In addition, as adult neurogenesis appears to participate to a greater extent in retrieval and extinction of recent (<48 hr posttraining) versus remote (>1 week posttraining) memories, we specifically examined the role of adult neurogenesis in reward‐associated contextual memories probed at recent and remote timepoints. Six weeks post‐IG‐IR or Sham treatment, mice underwent morphine CPP. Using separate groups, retrieval of recent and remote reward memories was found to be similar between IG‐IR and Sham treatments. Interestingly, IG‐IR mice showed impaired extinction—or increased persistence—of the morphine‐associated reward memory when it was probed 24‐hr (recent) but not 3‐weeks (remote) postconditioning relative to Sham mice. Taken together, these data show that hippocampal‐directed irradiation and the associated decrease in dentate gyrus adult neurogenesis affect the persistence of recently—but not remotely—probed reward memory. These data indicate a novel role for adult neurogenesis in reward‐based memories and particularly the extinction rate of these memories. Consideration of this work may lead to better understanding of extinction‐based behavioral interventions for psychiatric conditions characterized by dysregulated reward processing.
Overlap between hippocampal pre‐encoding and encoding patterns supports episodic memory
Authors: Sadeh Talya , Chen Janice , Goshen‐Gottstein Yonatan , Moscovitch Morris
Published: February 2019

It is well‐established that whether the information will be remembered or not depends on the extent to which the learning context is reinstated during post‐encoding rest and/or at retrieval. It has yet to be determined, however, if the fundamental importance of contextual reinstatement to memory extends to periods of spontaneous neurocognitive activity prior to learning. We thus asked whether memory performance can be predicted by the extent to which spontaneous pre‐encoding neural patterns resemble patterns elicited during encoding. Individuals studied and retrieved lists of words while undergoing fMRI‐scanning. Multivoxel hippocampal patterns during resting periods prior to encoding resembled hippocampal patterns at encoding most strongly for items that were subsequently remembered. Furthermore, across subjects, the magnitude of similarity correlated with a behavioral measure of episodic recall. The results indicate that the neural context before learning is an important determinant of memory.
Economic precariousness: A new channel in the housing market cycle
Authors: Arestis Philip , Gonzalez‐Martinez Ana Rosa
Published: February 2019

Demographic and institutional elements, as important drivers of the housing market, should not be neglected because it is not only financial and monetary elements that matter in the case of the housing market. In this context, one relationship, which still remains unclear, is the relationship between the housing and the labour markets. Some research has been undertaken to support the hypothesis that high rates of homeownership lead to high unemployment via increases in the reservation wage. However, further research is needed to address the possible implications of the institutional settings of the labour market in the dynamics of the housing market. The aim of this paper is to bring some light on the link between both markets. In particular, this contribution explains how the housing cycle could be “amplified” via a new channel, that is, economic precariousness, which is closely related to job insecurity. Subsequently, we provide evidence in the case of five developed economies, Ireland, the Netherlands, Spain, the United Kingdom, and the United States, over the period 1985–2013.
Measuring local properties inside a cell‐mimicking structure using rotating optical tweezers
Authors: Zhang Shu , Gibson Lachlan J. , Stilgoe Alexander B. , Nieminen Timo A. , Rubinsztein‐Dunlop Halina
Published: February 2019

Exploring the rheological properties of intracellular materials is essential for understanding cellular and subcellular processes. Optical traps have been widely used for physical manipulation of micro and nano objects within fluids enabling studies of biological systems. However, experiments remain challenging as it is unclear how the probe particle's mobility is influenced by the nearby membranes and organelles. We use liposomes (unilamellar lipid vesicles) as a simple biomimetic model of living cells, together with a trapped particle rotated by optical tweezers to study mechanical and rheological properties inside a liposome both theoretically and experimentally. Here, we demonstrate that this system has the capacity to predict the hydrodynamic interaction between three‐dimensional spatial membranes and internal probe particles within submicron distances, and it has the potential to aid in the design of high resolution optical micro/nanorheology techniques to be used inside living cells.
Evaluation of the mechanisms and effects of Mg–Ag–Y alloy on the tumor growth and metastasis of the MG63 osteosarcoma cell line
Authors: Dai Yilong , Tang Yifu , Xu Xuemei , Luo Zhongwei , Zhang Yu , Li Zhaohui , Lin Zhangyuan , Zhao Shushan , Zeng Min , Sun Buhua , Cheng Liang , Zhu Jianxi , Xiong Zeng , Long Haitao , Zhu Yong , Yu Kun
Published: February 2019

Osteosarcoma is a malignant primary bone tumor, which often associates with pulmonary metastasis. The radical surgery of osteosarcoma often requires internal orthopedic implants. Therefore, implants with antitumor properties should be developed. Magnesium (Mg) and its alloys possess great potential as orthopedic materials, given their biodegradable properties, superior osteogenesis performance, and antitumor features. However, problems arise with their uncontrolled degradation rates and their unknown antitumor mechanisms. In our study, when compared with pure Mg, the rare element silver alloyed with yttrium (Ag–Y) could extremely enhance the corrosion resistance of these elements, giving the Ex–Mg–1Ag–1Y alloy better anticorrosion rates. Here, we implanted the Ex–Mg–1Ag–1Y alloy and pure Mg and Ti alloy in vivo around tumors in nude mice (BALB/c). Notably, the local tumor weight in Mg alloy and pure Mg groups were much smaller than that in Ti alloy group in 36 days after surgery (6.59 ± 0.70, 6.76 ± 0.62, and 8.54 ± 0.56 g), while the general scores of lung metastasis in Mg alloy and pure Mg groups were also lower than Ti alloy group (64.50 ± 7.64, 62.73 ± 7.84, and 87.60 ± 9.43). Therefore, the Mg and Ex–Mg–1Ag–1Y alloy, both demonstrated resisting effects against local tumor growth and pulmonary metastasis, which could be performed by changing the extracellular acidosis microenvironment, elevating the Mg concentration, suppressing C–X–C chemokine receptor type 4 (CXCR4) levels, and increasing prostacyclin (PGI2) synthesis. Our work revealed that the Ex–Mg–1Ag–1Y alloy may be a promising orthopedic implant for treating osteosarcoma due to its better corrosion resistance and antitumor attributes. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2537–2548, 2019.
Cost-Effectiveness of Osteoporosis Screening Using Biomechanical Computed Tomography for Patients With a Previous Abdominal CT
Authors: Pisu Maria , Kopperdahl David L , Lewis Cora E , Saag Kenneth G , Keaveny Tony M
Published: February 2019

Osteoporosis screening rates by DXA are low (9.5% women, 1.7% men) in the US Medicare population aged 65 years and older. Addressing this care gap, we estimated the benefits of a validated osteoporosis diagnostic test suitable for patients age 65 years and older with an abdominal computed tomography (CT) scan taken for any indication but without a recent DXA. Our analysis assessed a hypothetical cohort of 1000 such patients in a given year, and followed them for 5 years. Separately for each sex, we used Markov modeling to compare two mutually exclusive scenarios: (i) utilizing the CT scans, perform one-time “biomechanical computed tomography” (BCT) analysis to identify high-risk patients on the basis of both femoral strength and hip BMD T-scores; (ii) ignore the CT scan, and rely instead on usual care, consisting of future annual DXA screening at typical Medicare rates. For patients with findings indicative of osteoporosis, 50% underwent 2 years of treatment with alendronate. We found that BCT provided greater clinical benefit at lower cost for both sexes than usual care. In our base case, compared to usual care, BCT prevented hip fractures over a 5-year window (3.1 per 1000 women; 1.9 per 1000 men) and increased quality-adjusted life years (2.95 per 1000 women; 1.48 per 1000 men). Efficacy and savings increased further for higher-risk patient pools, greater treatment adherence, and longer treatment duration. When the sensitivity and specificity of BCT were set to those for DXA, the prevented hip fractures versus usual care remained high (2.7 per 1000 women; 1.5 per 1000 men), indicating the importance of high screening rates on clinical efficacy. Therefore, for patients with a previously taken abdominal CT and without a recent DXA, osteoporosis screening using biomechanical computed tomography may be a cost-effective alternative to current usual care. © 2019 American Society for Bone and Mineral Research.
Osteogenic Dkk1 Mediates Glucocorticoid-Induced but Not Arthritis-Induced Bone Loss
Authors: Colditz Juliane , Thiele Sylvia , Baschant Ulrike , Garbe Annette I , Niehrs Christof , Hofbauer Lorenz C , Rauner Martina
Published: February 2019

Dickkopf-1 (Dkk1) is a negative regulator of bone formation and bone mass and is deregulated in bone loss induced by arthritis and glucocorticoid (GC) exposure. However, the role of Dkk1 in these pathological processes is still unknown. Here, we used conditional Dkk1 knock-out mice to determine the role of Dkk1 produced by osteolineage cells in the development of arthritis and GC-induced bone loss. Osteoprogenitor (Osx-Cre)- and osteocyte (Dmp1-Cre)-specific knock-out mice and their Cre-negative controls were subjected to two arthritis models, K/BxN and antigen-induced arthritis. Disease induction and progression were assessed. GC-induced bone loss was induced in 25-week-old female mice by implanting prednisolone (7.5 mg) slow-release pellets for 4 weeks. Dkk1fl/fl;Osx-Cre mice subjected to K/BxN arthritis showed mildly reduced disease severity with reduced infiltration of neutrophils and T cells into affected joints and reduced bone erosions compared with Cre-negative controls. Osteocyte-specific Dkk1 deletion did not affect disease severity or local bone erosions. However, systemic bone loss at the spine was less severe in both mouse lines. In contrast to arthritis, both lines were protected from GC-induced bone loss. Although the Cre-negative controls lost about 26% and 31% bone volume potentially caused by decreased bone formation, Cre-positive mice did not exhibit such alterations. Dkk-1 deficiency in osteolineage cells protects against GC-induced bone loss, whereas it had only minor effects in arthritis. Therefore, Dkk1 may be a promising therapeutic target especially for bone diseases in which inhibition of bone formation represents the predominant mechanism. © 2019 American Society for Bone and Mineral Research.
Involvement of PI3K/Akt pathway in the protective effect of hesperidin against a chemically induced liver cancer in rats
Authors: Mo’men Yomna S. , Hussein Rasha M. , Kandeil Mohamed A.
Published: February 2019

Hesperidin is a flavanone glycoside that is found in the Citrus species and showed antioxidant, hepatoprotective as well as anticancer activity. This study investigated the effect of hesperidin on the PI3K/Akt pathway as a possible mechanism for its protective effect against diethylnitrosamine (DEN)‐induced hepatocellular carcinoma (HCC). Adult Wistar rats were divided into Control group (received drug vehicle); DEN group (received 100 mg/L of DEN solution for 8 weeks), and hesperidin + DEN group (received 200 mg/kg body weight of hesperidin/day orally for 16 weeks + DEN solution as DEN group). Our findings showed that the administration of hesperidin significantly decreased the elevation in liver function enzymes, serum AFP level, and oxidative stress markers. Moreover, hesperidin administration suppressed DEN‐induced upregulation of PI3K, Akt, CDK‐2 protein expression, and preserved the integrity of the liver tissues from HCC formation. In conclusion, the hepatoprotective activity of hesperidin is mediated via its antioxidation and downregulation of the PI3K/Akt pathway.
PPAR‐γ: Its ligand and its regulation by microRNAs
Authors: Seiri Parvaneh , Abi Abbas , Soukhtanloo Mohammad
Published: February 2019

Peroxisome proliferator‐activated receptors (PPARs) belong to the nuclear receptor superfamily. PPARs are categorized into three subtypes, PPARα, β/δ, and γ, encoded by different genes, expressed in diverse tissues and participate in various biological functions and can be activated by their metabolic derivatives in the body or dietary fatty acids. The PPAR‐γ also takes parts in the regulation of energy balance, lipoprotein metabolism, insulin sensitivity, oxidative stress, and inflammatory signaling. It has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancers. Among various cellular and molecular targets that are able to regulate PPAR‐γ and its underlying pathways, microRNAs (miRNAs) appeared as important regulators. Given that the deregulation of these molecules via targeting PPAR‐γ could affect initiation and progression of various diseases, identification of miRNAs that affects PPAR‐γ could contribute to the better understanding of roles of PPAR‐γ in various biological and pathological conditions. Here, we have summarized the function and various ligands of PPAR‐γ and have highlighted various miRNAs involved in the regulation of PPAR‐γ.
The skewed frequency of B‐cell subpopulation CD19+CD24hiCD38hi cells in peripheral blood mononuclear cells is correlated with the elevated serum sCD40L in patients with active systemic lupus erythematosus
Authors: Wang Huiming , Liu Changxuan , Chen Wenli , Ding Guohua
Published: February 2019

CD19+CD24hiCD38hi cells play an essential role in maintaining immune homeostasis. CD40 signaling is involved in regulating the induction and function of CD19+CD24hiCD38hi cells. Changes in B‐cell subpopulations and CD19+CD24hiCD38hi cells have been observed in systemic lupus erythematosus (SLE) patients. Whether changes in the B‐cell subpopulation are related to the aberrant CD40 signaling in SLE patients remains unclear. In this study, we examined changes in the levels of CD19+CD24hiCD38hi cells and CD19+CD24hiCD38low cells in peripheral blood mononuclear cells and the serum level of soluble CD40 ligand (sCD40L) in 30 patients with SLE. Through routine biochemical assays and flow cytometry assay, we found that (1) the CD19+CD24hiCD38hi cell subset was upregulated in SLE patients compared to that in healthy controls (HCs) (P < 0.05); (2) the CD19+CD24hiCD38low cell subset was downregulated in SLE patients compared with that in HCs; and (3) CD38 expression was positively correlated with SLE manifestations and the serum sCD40L level (P < 0.05). In conclusion, the relative level of Bregs is significantly higher in SLE patients than in HCs and is positively correlated with disease activity and sCD40L level.
Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride‐induced hepatotoxicity in rats
Authors: Yousefi‐Manesh Hasan , Shirooie Samira , Partoazar Alireza , Nikoui Vahid , Estakhri Mohammad Reza Abdollahzadeh , Bakhtiarian Azam
Published: February 2019

It has been proposed carbon tetrachloride (CCl4) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl4‐induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl4 (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl4 significantly inhibited alterations in the serum levels of AST, ALP (**P < 0.01), and ALT (***P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl4‐induced hepatotoxicity in rats.
Theoretical studies on triaryamine‐based p‐type D‐D‐π‐A sensitizer
Authors: Kong Li‐Xiao , He Mingfei , Yan Wen , Zhang Chang‐Shan , Ju Xue‐Hai
Published: February 2019

Development of triaryamine‐based nonmetallic dye sensitizers is a hot topic in the solar cell research. A series of triaryamine‐based dyes WS1–WS7 were designed with W1 as the prototype. Density functional theory (DFT) and time‐dependent‐DFT calculations were used to investigate the effects of the attached donor D on the absorption spectra and electronic properties of the dyes. The light‐harvesting efficiency (LHE), hole injection force (ΔGinj), dye regeneration force (ΔGreg), and charge recombination force (ΔGCR) for all the dyes were predicted. The insertion of D not only results in a red shift in the absorption spectra for all dyes but also achieves a broader absorption for visible light. Compared with that of the prototype, the absorption peak of the dye WS7 has a red shift of 95 nm and an oscillator strength increase of 29%. The absorption peak of WS7 is wider and stronger, and the absorption range extends to 900 nm. The LHE and ΔGreg values of WS7 are 0.991 and −1.49 eV, respectively. On overall evaluation, WS7 is a promising candidate of a p‐type dye sensitizer with good light absorption and dye regeneration efficiency.
Determination of hemolysis index thresholds for biochemical tests on Siemens Advia 2400 chemistry analyzer
Authors: Du Zhenhua , Liu JiQin , Zhang Hua , Bao BuHe , Zhao RuiQi , Jin Ying
Published: February 2019

Background

In vitro hemolysis is still the most common source of pre‐analytical nonconformities. This study aimed to investigate the hemolytic effects on commonly used biochemical tests as well as to determine the hemolysis index (HI) thresholds on Siemens Advia 2400 chemistry analyzer.

Methods

Peripheral blood samples were collected from forty healthy volunteers. Hemolysis was achieved using syringes. Five hemolysis levels were produced including the no hemolysis group, slight hemolysis group, mild hemolysis group, moderate hemolysis group, and heavy hemolysis group. We then used the bias from baseline (no hemolysis) and HI to construct regression functions. The HI corresponding to the bias limits was considered as HI thresholds. We chose the total allowable error (TAE) as the bias limit.

Results

Of the twenty‐eight analytes, ten analytes had clinical significance. Creatine kinase‐MB, creatine kinase, potassium, aspartate aminotransferase, and hydroxybutyrate dehydrogenase were all positively affected; the corresponding HI threshold was 45.2, 99.96, 4.07, 10.16, and 7.94, respectively. Lactate dehydrogenase was also positively interfered, but we failed to calculate the HI threshold. Total bile acid, uric acid, and sodium were all negatively affected, and the HI threshold was 42.23, 500 and 501.8, respectively. Glucose was also negatively interfered, but it failed to achieve the HI threshold.

Conclusions

When the HI value was higher than its threshold, the corresponding analyte was considered inappropriate for reporting. The implementation of the assay‐specific HI thresholds could provide an accurate method to identify analytes interfered by hemolysis, which would improve clinical interpretations and further boost laboratory quality by reducing errors associated with hemolysis.
Distribution of serum neuron‐specific enolase and the establishment of a population reference interval in healthy adults
Authors: Liu Qian , Fan Jilong , Xu Aiguo , Yao Li , Li Yan , Wang Wenjun , Liang Wei , Yang Fumeng
Published: February 2019

Background

Neuron‐specific enolase (NSE) is an important tumor marker in the serum of patients with lung cancer. Elevated serum NSE levels are also associated with many other diseases. However, there is no unified population reference interval for serum NSE. This study aimed to investigate the distribution of serum NSE in healthy Chinese adults aged 20‐79 years and to establish its reference interval in Chinese population.

Methods

A total of 10 575 healthy subjects were in line with the requirements of this study. The concentration of serum NSE was detected by a fully automated Cobas e602 analyzer with matching reagents. The population reference interval for serum NSE was established using the unilateral 95th percentile (P95) according to standard guidelines.

Results

The distributions of serum NSE were not significantly different between males and females (P > 0.05) and also did not differ by age (P > 0.05). Therefore, the population reference interval for serum NSE was established as upper limit 25.4 ng/mL (90% confidence interval: 24.5‐26.2 ng/mL).

Conclusions

We established the first population reference interval for serum NSE in a large healthy Chinese adult cohort, which was higher than that recommended by Roche Diagnostics GmbH. This new reference interval is more practical and applicable in Chinese adults.
Empathy and social closeness toward refugees from Syria: The mediating role of cultural intelligence
Authors: Pawlicka Paulina , Kazmierczak Maria , Jagiello‐Rusilowski Adam
Published: February 2019

The predictors of social closeness toward refugees are rarely examined. In this study (N = 337), higher cultural intelligence (CQ) and higher empathy were defined as predictors of higher social closeness (lower social distance [the Social Distance Scale] and warmer feelings [the Feeling Thermometer]) toward refugees from Syria. This is the target group of prejudice and intensive coverage in the European mass media. The obtained results indicated that other‐oriented empathy (empathic concern and perspective taking) and the motivational CQ predicted higher social closeness and warmer feelings toward refugees from Syria. Empathic personal distress predicted lower social closeness and colder feelings toward this group. Motivational CQ consistently served as the mediator of the relationship between empathy dimensions and social closeness toward Syrian refugees. Our findings reveal the previously unexplored correlations between empathy dimensions and cultural intelligence factors, including the mediational effects in predicting social closeness toward Syrian refugees.
High throughput circRNAs sequencing profile of follicle fluid exosomes of polycystic ovary syndrome patients
Authors: Wang Li‐ping , Peng Xiao‐yu , Lv Xiao‐qin , Liu Lin , Li Xue‐li , He Xiao , Lv Fang , Pan Yu , Wang Li , Liu Kai‐feng , Zhang Xiao‐mei
Published: February 2019

Polycystic ovary syndrome (PCOS) is one of the most prevalent reproductive disorders in women worldwide. Despite rigorous research, the exact molecular mechanism that governs PCOS pathogenesis remains unclear. To investigate the potential roles of circular RNAs (circRNAs), this study sequenced ribosomal RNA‐depleted total RNA from exosomes of follicle fluids obtained from PCOS patients using non‐PCOS samples as controls. Bioinformatic analysis identified 167 upregulated and 245 downregulated circRNAs from a total of 16,771 detected candidates. Functional analysis suggests that pathways related to bacterial infection, associated chronic inflammation, and oxidative stress could be targeted by the differential circRNAs in PCOS patients. The obtained sequencing results were further validated by quantitative reverse‐transcription polymerase chain reaction and a circRNA–microRNA interaction network was constructed. The obtained results provide a valuable addition to the published studies on the mechanism of PCOS pathogenesis by revealing a wide variety of new circRNAs, miRNA, and gene targets that merit further investigation.
Retracted: Ras–ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac
Authors: Li Yaping , Sun Weixuan , Sun Dajun , Yin Dexin
Published: February 2019

Ras–extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) signaling has been proposed as the crucial regulators in the development of various cancers. Histone acetylation at H3 lysine 14 (H3K14ac) is closely associated with gene expression and DNA damage. However, whether H3K14ac participates in mediating Ras–ERK1/2‐induced cell proliferation and migration in uveal melanoma cells remains unknown. The purpose of this study is to investigate the effect of H3K14ac on Ras–ERK1/2 affected uveal melanoma cell phenotypes. MP65 cells were transfected with Ras
WT and Ras
G12V/T35S, the unloaded plasmid of pEGFP‐N1 served as a negative control. Protein levels of phosphorylated ERK1/2
Thr202 and H3K14ac were assessed by western blot assay. Cell viability, number of colonies, migration, and the downstream genes of ERK1/2 were analyzed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, soft‐agar colony formation, transwell, and chromatin immunoprecipitation assays. HA‐tag vectors of CLR3 and TIP60 and the small interfering RNAs that specific for CLR3 and MDM2 were transfected into MP65 cells to uncover the effects of CLR3, TIP60, and MDM2 on Ras–ERK1/2 mediated H3K14ac expression and MP65 cell phenotypes. We found that, Ras–ERK1/2 decreased H3K14ac expression in MP65 cells, and H3K14ac significantly suppressed Ras–ERK1/2‐induced cell viability, colony formation, and migration in MP65 cells. Moreover, the transcription of CYR61, IGFBP3, WNT16B, NT5E, GDF15, and CARD16 was regulated by H3K14ac. Additionally, CLR3 silence recovered H3K14ac expression and reversed the effect of Ras–ERK1/2 on MP65 cell proliferation, migration and the mRNAs of ERK1/2 downstream genes. Besides, Ras–ERK1/2 decreased H3K14ac expression by MDM2‐mediated TIP60 degradation. In conclusion, Ras–ERK1/2 promoted uveal melanoma cells growth and migration by downregulating H3K14ac via MDM2‐mediated TIP60 degradation.
Expression pattern of microRNAs related with response to trastuzumab in breast cancer
Authors: Yang Fan , Fu Ziyi , Yang Mengzhu , Sun Chunxiao , Li Yongfei , Chu Jiahui , Zhang Yanhong , Li Wei , Huang Xiang , Li Jun , Wu Hao , Ding Xiaorong , Yin Yongmei
Published: February 2019

Background

Although an immense effort has been made to develop a novel biomarker for response to trastuzumab, no reliable biomarkers are available to guide management, expect for HER2. The aim of this study was to examine the relationship between microRNA (miRNA) expression and resistance to trastuzumab.

Methods

Differentially expressed miRNAs between trastuzumab‐resistant and trastuzumab‐sensitive cell lines were analyzed using microarrays. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to determine the functions of differentially expressed miRNA and their targeted genes. Furthermore, the protein–protein interactions (PPI) network was analyzed. Serum samples were collected from patients with HER2‐positive breast cancer who were treated with trastuzumab. We validated the miRNAs expression levels by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) in these serums. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the miRNA.

Results

Using miRNA microarrays, 151 miRNAs that significant differentially expressed between the trastuzumab‐resistant and sensitive cells were identified, including 46 upregulated and 105 downregulated miRNAs. Results of real‐time PCR confirmed seven miRNAs in cell lines. PI3K‐Akt signaling pathway was involved in regulating biological function according to KEGG analysis. Compared with the serums of trastuzumab‐sensitive patients, three miRNAs, namely miR‐200b, miR‐135b, and miR‐29a, were identified to be upregulated, and miR‐224 was downregulated in the trastuzumab‐resistant serums. ROC analysis showed that four miRNAs were correlated with trastuzumab resistance. Furthermore, three subnetwork modules of PPI network were obtained.

Conclusion

The results indicated that miRNAs were reliable predictive biomarkers for response to trastuzumab.
Memory and CAR‐NK cell‐based novel approaches for HIV vaccination and eradication
Authors: Mazarzaei Abdulbaset , Vafaei Mahtab , Ghasemian Abdolmajid , Mirforughi Seyede Amene , Rajabi Vardanjani Hassan , Alwan Nada A. S.
Published: February 2019

Human immunodeficiency virus (HIV) is one of the critical infectious agents with thousands of newly infected people worldwide. High mutational capability and rapid diversification, inhibition of humoral and cellular immune responses, and thus inability for recognition of an immunogenic region in the viral envelope by the immune system are major challenges. Natural killer (NK) cells are multifunctional, playing a key role in the identification and elimination of HIV‐infected cells. These cells identify and eliminate virus‐infected cells in a multilateral manner, such as ligand stress, antibody‐dependent cell cytotoxicity (ADCC), T follicular helper (Tfh), and the activation of most of the stimulatory receptors. Moreover, these cells release cytokines leading to the activation of cytotoxic lymphocytes (CTLs) and dendritic cells (DCs), contributing to efficient viral elimination. Some subsets of NK cells exhibit putatively enhanced effector functions against viruses following vaccination easily expanded and identified by NK cell lines culture. Furthermore, NK cells promote the elimination of HIV‐infected cells which reduce the expression of major histocompatibility complex (MHC) molecules. Memory NK cells have higher functionality and renewable potential. A pioneering strategy to establish an efficacious HIV vaccine would include stimulation of the accumulation and long‐term maintenance of these HIV‐reactive NK cells. CAR‐NK (chimeric antigen receptor‐natural killer) cells‐based antiviral therapies have emerged as novel approaches with the ability of antigen recognition and more advantages than CAR‐T (chimeric antigen receptor‐T) cells. Recent development of induced pluripotent stem cell (iPSC)‐derived NK cells with enhanced activity and efficiency conferred a promising insight into CAR‐NK cell‐based therapies. Therefore, memory and CAR‐NK cells‐based approaches can emerge as novel strategies providing implications for HIV vaccine design and therapy.
The overexpression of GRASP might inhibit cell proliferation and invasion in hepatocellular carcinoma
Authors: Cheng Yang , Yin Baobing , Hou Tianlu , Chen Tianyang , Ping Jian
Published: February 2019

This study aimed to validate the methylation of key genes in hepatocellular carcinoma (HCC) screened by bioinformatics analysis and explore whether they affected HCC cell proliferation, migration, and invasion. Using The Cancer Genome Atlas (TCGA) database, HCC‐related differentially methylated positions (DMPs) were screened, genes corresponding to DMPs were selected, and prognosis‐related genes were identified. A representative DMP was used to divide the DMPs into hyper‐ and hypomethylated groups. Expression of key genes in cell lines was detected using quantitative real‐time polymerase chain reaction and western blot analysis. After treatment of HepG2 cells with 5‐Aza‐2′‐deoxycytidine (5‐Aza‐DC), gene expression was observed. Bisulfite sequencing PCR assay was used to detect methylation frequency. Overexpressed GRASP lentiviral vectors were constructed to analyze their influence on cell proliferation, migration, and invasion using cell counting kit‐8 and transwell assays. Forty‐three HCC prognosis‐related genes were screened using the TCGA database. cg00249511 (SCT) was used to divide the DMPs into hyper‐ and hypomethylated groups, distinguishing between high‐ and low‐risk samples. The prognosis survival model constructed using 12 genes revealed the prognosis type. GRASP messenger RNA was downregulated in HepG2 and upregulated after 5‐Aza‐DC treatment. In HCC tissues, methylation frequency of GRASP was upregulated. GRASP overexpression inhibited HepG2 cell proliferation, invasion, and G‐CSFR expression. Thus, GRASP might be a prognosis‐related gene controlled by methylation.
Design and synthesis of novel celastrol derivative and its antitumor activity in hepatoma cells and antiangiogenic activity in zebrafish
Authors: Wang Gang , Xiao Qi , Wu Yao , Wei Ying‐jie , Jing Yue , Cao Xiang‐rong , Gong Zhu‐nan
Published: February 2019

Two series of celastrol derivatives were designed and synthesized by modifying carboxylic acid at the 28th position with amino acid, and their intermediates with isobutyrate at the third position. All compounds were evaluated for their antiproliferation activity by four human cancer cell lines (SCG7901, HGC27, HepG2, and Bel7402) and one normal cell LO2. The most promising compound, compound 8, showed superior bioactivity and lower toxicity than others including celastrol. Further underlying tests illustrated that compound 8 induced apoptosis and cell arrest at G2/M and inhibited proliferation and mobility of human hepatoma cells by suppressing the signal transducer and activator of transcription‐3 signaling pathway. Besides these, a highly accurate and reproducible high performance liquid chromatography protocol was established to determine celastrol and compound 8 absorption in zebrafish, and results demonstrated that their concentration increased rapidly within 4 hr in a time‐dependent manner and the concentration of compound 8 was higher than that of celastrol. In addition, without detection at 12 hr, compound 8 was rapidly metabolized in vivo. These findings are very helpful for the structural modification of celastrol and other bioactive compounds to improve their bioactivity, toxicity, and absorption.
Characterization of canine adipose tissue‐derived mesenchymal stem cells immortalized by SV40‐T retrovirus for therapeutic use
Authors: Ayala‐Cuellar Ana Patricia , Kim Cho‐Won , Hwang Kyung‐A , Kang Ji‐Houn , Lee Gabsang , Cho Jaejin , Choi Kyung‐Chul
Published: February 2019

Canine mesenchymal stem cells (cMSCs) are gaining popularity in the veterinary field as a regenerative therapy. But, their limited culture lifespan makes it an obstacle for preclinical investigation and therapeutic use. In this study, primary canine adipose tissue‐derived MSCs (PCAT‐MSCs) were isolated from adipose tissue and were transfected with the SV40‐T retrovirus resulting in a life‐extended immortalized canine adipose tissue‐derived MSCs (ICAT‐MSCs). A comparison was made through the characterization of both PCAT‐MSCs and ICAT‐MSCs. Both showed a fibroblastic morphology; ICAT‐MSCs showed a higher potential of colony formation compared with PCAT‐MSCs and a reduced population doubling time; stem cell markers SOX2 and NANOG were expressed in both cell lines; karyotyping analysis showed no abnormalities in both PCAT‐MSCs and ICAT‐MSCs; both cell lines were CD90+, CD44
+, and CD45
−; both generated chondrogenic pellet; in osteogenic differentiation both showed upregulation of Osterix, a master transcriptome of osteogenesis, but in PCAT‐MSCs, an upregulation of SOX2 was also observed. In conclusion, ICAT‐MSCs showed similar characteristics with PCAT‐MSCs, thus established as an easy to access platform for studies on better understanding about cMSCs nature.
The OXPHOS supercomplex assembly factor HIG2A responds to changes in energetic metabolism and cell cycle
Authors: Salazar Celia , Elorza Alvaro A. , Cofre Glenda , Ruiz‐Hincapie Paula , Shirihai Orian , Ruiz Lina María
Published: February 2019

HIG2A promotes cell survival under hypoxia and mediates the assembly of complex III and complex IV into respiratory chain supercomplexes. In the present study, we show that human HIGD2A and mouse Higd2a gene expressions are regulated by hypoxia, glucose, and the cell cycle‐related transcription factor E2F1. The latter was found to bind the promoter region of HIGD2A. Differential expression of the HIGD2A gene was found in C57BL/6 mice in relation to tissue and age. Besides, the silencing of HIGD2A evidenced the modulation of mitochondrial dynamics proteins namely, OPA1 as a fusion protein increases, while FIS1, a fission protein, decreases. Besides, the mitochondrial membrane potential (ΔΨm) increased. The protein HIG2A is localized in the mitochondria and nucleus. Moreover, we observed that the HIG2A protein interacts with OPA1. Changes in oxygen concentration, glucose availability, and cell cycle regulate HIGD2A expression. Alterations in HIGD2A expression are associated with changes in mitochondrial physiology.
miR‐193: A new weapon against cancer
Authors: Khordadmehr Monireh , Shahbazi Roya , Sadreddini Sanam , Baradaran Behzad
Published: February 2019

microRNAs (miRNAs) are known as a large group of short noncoding RNAs, which structurally consist of 19–22 nucleotides in length and functionally act as one of the main regulators of gene expression in important biological and physiological contexts like cell growth, apoptosis, proliferation, differentiation, movement (cell motility), and angiogenesis as well as disease formation and progression importantly in cancer cell invasion, migration, and metastasis. Among these notable tiny molecules, many studies recently presented the important role of the miR‐193 family comprising miR‐193a‐3p, miR‐193a‐5p, miR‐193b‐3p, and miR‐193b‐5p in health and disease biological processes by interaction with special targeting and signaling, which mainly contribute as a tumor suppressor. Therefore, in the present paper, we review the functional role of this miRNA family in both health and disease conditions focusing on various tumor developments, diagnoses, prognoses, and treatment.
Bayesian methods applied to the generalized matching law
Authors: Villarreal Manuel , Velázquez Carlos , Baroja José L. , Segura Alejandro , Bouzas Arturo , Lee Michael D.
Published: February 2019

We demonstrate the usefulness of Bayesian methods in developing, evaluating, and using psychological models in the experimental analysis of behavior. We do this through a case study, involving new experimental data that measure the response count and time allocation behavior in pigeons under concurrent random‐ratio random‐interval schedules of reinforcement. To analyze these data, we implement a series of behavioral models, based on the generalized matching law, as graphical models, and use computational methods to perform fully Bayesian inference. We demonstrate how Bayesian methods, implemented in this way, make inferences about parameters representing psychological variables, how they test the descriptive adequacy of models as accounts of behavior, and how they compare multiple competing models. We also demonstrate how the Bayesian graphical modeling approach allows for more complicated modeling structures, including hierarchical, common cause, and latent mixture structures, to formalize more complicated behavioral models. As part of the case study, we demonstrate how the statistical properties of Bayesian methods allow them to provide more direct and intuitive tests of theories and hypotheses, and how they support the creative and exploratory development of new theories and models.
Bayesian data analysis as a tool for behavior analysts
Authors: Young Michael E.
Published: February 2019

Bayesian approaches to data analysis are considered within the context of behavior analysis. The paper distinguishes between Bayesian inference, the use of Bayes Factors, and Bayesian data analysis using specialized tools. Given the importance of prior beliefs to these approaches, the review addresses those situations in which priors have a big effect on the outcome (Bayes Factors) versus a smaller effect (parameter estimation). Although there are many advantages to Bayesian data analysis from a philosophical perspective, in many cases a behavior analyst can be reasonably well‐served by the adoption of traditional statistical tools as long as the focus is on parameter estimation and model comparison, not null hypothesis significance testing. A strong case for Bayesian analysis exists under specific conditions: When prior beliefs can help narrow parameter estimates (an especially important issue given the small sample sizes common in behavior analysis) and when an analysis cannot easily be conducted using traditional approaches (e.g., repeated measures censored regression).
Beyond esterase‐like activity of serum albumin. Histidine‐(nitro)phenol radical formation in conversion cascade of p‐nitrophenyl acetate and the role of infrared light
Authors: Kowacz Magdalena , Warszyński Piotr
Published: February 2019

Serum albumin, recognized mainly for its capacity to act as a carrier protein for many compounds, can also actively transform some organic molecules. As a starting point in this study, we consider esterase‐like activity of bovine serum albumin (BSA) toward p‐nitrophenyl acetate (p‐NPA). Our results reveal that the reaction goes beyond ester hydrolysis step. In fact, the transformation product, p‐nitrophenol (p‐NP), becomes a substrate for further reaction with BSA in which its nitro group in subtracted and released in the form of HNO2. Spectral data indicate that this cascade of events proceeds through formation of phenoxyl radical via proton‐coupled electron transport (PCET) between OH group of p‐NP and imidazole ring of histidine from the protein. Furthermore, the effect of application of electromagnetic radiation in the infrared range suggests that this remote physical trigger can support interactions based on PCET mechanism by acting on polarization and mutual alignment of water dipoles serving as effective water wires.