bluuebunny/crossref_metadata_2025 huggingface dataset:
3D‐printed Electrodes for Sensing of Biologically Active Molecules
Authors: Liyarita Bella Rosa , Ambrosi Adriano , Pumera Martin
Published: January 2018

3D printing (additive manufacturing) is currently an emerging technology that could revolutionize the traditional manufacturing process. The application of 3D printing technology has been examined in many different fields including manufacturing, science, medicine, and electronics. Another application of 3D printing technology which holds promising potential is fabrication of electrochemical sensors and transducers. Electroanalytical devices hold advantages such as low cost, portability, ease of use, and rapid analysis. Here we examined the feasibility of utilizing 3D‐printed metal electrodes for the electrochemical detection of the pain reliever acetaminophen (AC) also known as paracetamol and the neurotransmitter dopamine (DA) in aqueous solutions. 3D‐printed stainless steel helical‐shaped electrodes were tested before and after surface modification by electro‐plating with a thin gold film (3D gold).
Engineering aspects of immobilized lipases on esterification: A special emphasis of crowding, confinement and diffusion effects
Authors: Parashar Surendra Kumar , Srivastava Sunil Kumar , Dutta N. N. , Garlapati Vijay Kumar
Published: January 2018

Cross‐linked enzyme crystal (CLEC) and sol‐gel entrapped pseudomonas sp. lipase were investigated for the esterification of lauric acid with ethanol by considering the effects of reaction conditions on reaction rate. The activation energy for the reaction was estimated to be 1097.58 J/mol and 181.75 J/mol for sol‐gel and CLEC entrapped lipase respectively. CLEC lipase exhibited a marginal internal diffusion effect on reaction rate over sol‐gel lipases and found to be interesting. The overall reaction mechanism was found to conform to the Ping Pong Bi Bi mechanism. The higher efficiency of sol‐gel lipases over CLEC lipases in esterification reaction is mainly due to the combined effects of crowding, confinement and diffusional limitations.
Thermoeconomic analysis and optimization of post‐combustion CO2 recovery unit utilizing absorption refrigeration system for a natural‐gas‐fired power plant
Authors: Shirmohammadi Reza , Soltanieh Mohammad , Romeo Luis M.
Published: January 2018

Exergy and exergoeconomic analyses have been used to set out weaknesses of the postcombustion CO2 capture unit of Besat power plant that uses an ammonia absorption refrigeration system for CO2 liquefaction. The energy required for the absorption system is provided by the flue gas. The liquefied CO2 is used for beverage and food industries. The exergoeconomic costs of all utility streams and processes are calculated through a systematic method of assigning exergetic cost relations to the streams. The results point out that the exergy destruction of the CO2 stripper and absorber columns are the highest, and according to the cost‐based information, potential locations for the process improvement are proposed. A comprehensive method based on thermodynamic and mathematical methods has been proposed to acquire efficient design parameters and consumed power in compressors. It is based on a combination of Aspen HYSYS® and MATLAB® to do calculations and then an optimization procedure based on genetic algorithms. Results show that the production cost of each ton CO2 is equal to 6.05 (USD/ton) and return on investment can also be obtained by 2.5 years considering USD 1,600,000 of annual revenue. © 2018 American Institute of Chemical Engineers Environ Prog, 37: 1075–1084, 2018
Seismic performance of hybrid ductile‐rocking braced frame system
Authors: Binder Justin , Christopoulos Constantin
Published: January 2018

A new hybrid ductile‐rocking seismic‐resistant design is proposed which consists of a code‐designed buckling‐restrained braced frame (BRBF) that yields along its height and also partially rocks on its foundation. The goal of this system is to cost‐effectively improve the performance of BRBFs, by reducing drift concentrations and residual deformations, while taking advantage of their large ductility and their reliable limit on seismic forces and accelerations along a building's height. A lock‐up device ensures that the full code‐compliant lateral strength can be achieved after a limited amount of column uplift, and supplemental energy dissipation elements are used to reduce the rocking response. This paper outlines the mechanics of the system and then presents analyses on rocking frames with both ductile and elastic braces in order to highlight the large higher mode demands on elastic rocking frames. A parametric study using nonlinear time‐history analysis of BRBF structures designed according to the proposed procedure for Los Angeles, California is then presented. This study investigates the system's seismic response and the effect of different energy dissipation element properties and allowable base rotation values before the lock‐up is engaged. Finally, the effect of vertical mass modeling on analysis results was investigated. These studies demonstrated that the hybrid ductile‐rocking system can in fact improve the global peak and residual deformation response as well as reduce brace damage. This enhanced performance could eliminate the need for expensive repairs or demolition that are otherwise to be expected for conventional ductile fixed base buildings that sustain severe damage.
Tipping points in Texas rivers
Authors: Phillips Jonathan D.
Published: January 2018

Anticipating geomorphic tipping points requires that we learn from the past. Major geomorphic changes in coastal plain rivers of Texas resulting in river metamorphosis or regime shifts were identified and the major driving factors determined. Eleven such transformations – possible tipping points – were identified from contemporary observations, historical records, and Quaternary reconstructions. Two of the tipping points (between general aggrading and degrading valley states) are associated with reversals in a fundamental system control (sea‐level). One (stable or aggrading versus degrading channels) is associated with an abrupt change in sediment supply due to dam construction, and two others (changes from meandering to anastomosing channel patterns, and different anastomosis styles) are similarly related to changes in sediment supply and/or transport capacity, but with additional elements of historical contingency. Three tipping points are related to avulsions. One, from a regime dominated by re‐occupation of former channels to one dominated by progradation into flood basins, is driven by progressive long‐term filling of incised valleys. Another, nodal avulsions, is triggered by disturbances associated with tectonic uplift or listric faults. The third, avulsions and related valley metamorphosis in unfilled incised valleys, is due to fundamental dynamical instabilities within the fluvial system. This synthesis and analysis suggests that geomorphic tipping points are sometimes associated with general extrinsic or intrinsic (to the fluvial system) environmental change, independent of any disturbances or instabilities. Others are associated with natural (e.g. tectonic) or human (dams) disturbances, and still others with intrinsic geomorphic instabilities. This suggests future tipping points will be equally diverse with respect to their drivers and dynamics. Copyright © 2018 John Wiley & Sons, Ltd.
Before and After the Shoa
Authors: Unterstell Rembert
Published: January 2018

Michael Brenner studies modern Jewish history and culture from diverse perspectives. This also benefits his work as International President of the Leo Baeck Institute. An interview on paradigm shifts in German‐Jewish historiography, Theodor Herzl and Zionism, and challenging Israel Studies.
Breakdown in the temporal and spatial organization of spontaneous brain activity during general anesthesia
Authors: Zhang Jianfeng , Huang Zirui , Chen Yali , Zhang Jun , Ghinda Diana , Nikolova Yuliya , Wu Jinsong , Xu Jianghui , Bai Wenjie , Mao Ying , Yang Zhong , Duncan Niall , Qin Pengmin , Wang Hao , Chen Bing , Weng Xuchu , Northoff Georg
Published: January 2018

Which temporal features that can characterize different brain states (i.e., consciousness or unconsciousness) is a fundamental question in the neuroscience of consciousness. Using resting‐state functional magnetic resonance imaging (rs‐fMRI), we investigated the spatial patterns of two temporal features: the long‐range temporal correlations (LRTCs), measured by power‐law exponent (PLE), and temporal variability, measured by standard deviation (SD) during wakefulness and anesthetic‐induced unconsciousness. We found that both PLE and SD showed global reductions across the whole brain during anesthetic state comparing to wakefulness. Importantly, the relationship between PLE and SD was altered in anesthetic state, in terms of a spatial “decoupling.” This decoupling was mainly driven by a spatial pattern alteration of the PLE, rather than the SD, in the anesthetic state. Our results suggest differential physiological grounds of PLE and SD and highlight the functional importance of the topographical organization of LRTCs in maintaining an optimal spatiotemporal configuration of the neural dynamics during normal level of consciousness. The central role of the spatial distribution of LRTCs, reflecting temporo‐spatial nestedness, may support the recently introduced temporo‐spatial theory of consciousness (TTC).
Oncologic outcomes of extended neck dissections in human papillomavirus‐related oropharyngeal squamous cell carcinoma
Authors: Zenga Joseph , Pipkorn Patrik , Graboyes Evan M. , Martin Eliot J. , Rich Jason T. , Moore Eric J. , Haughey Bruce H. , Jackson Ryan S.
Published: January 2018

Background

Oncologic outcomes of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (SCC) requiring resection of major muscular or neurovascular tissue during neck dissection for invasive nodal disease remain uncertain.

Methods

Patients with HPV‐related oropharyngeal SCC requiring resection of major muscular or neurovascular tissue during their neck dissections were retrospectively identified.

Results

Seventy‐two patients were included. Regional and distant recurrences occurred in 6% and 17% of patients. Advanced T classification, pathological node number of 5 or more, and omission of adjuvant therapy were associated with decreased disease‐free survival (DFS). The addition of adjuvant chemotherapy was not associated with improved survival.

Conclusion

Patients with invasive nodal disease from HPV‐related oropharyngeal SCC can be managed with up‐front surgery and adjuvant therapy, as indicated with good regional control. Although distant recurrence was the primary site of failure, adjuvant chemotherapy was not associated with improved outcomes. The T classification, node number, and adjuvant radiotherapy are independent prognostic factors in this patient population.
Risk analysis of malignant potential of oral verrucous hyperplasia: A follow‐up study of 269 patients and copy number variation analysis
Authors: Wu Ming‐Heng , Luo Ji‐Dung , Wang Wen‐Chang , Chang Tzu‐Hao , Hwang Wei‐Lun , Lee Kuen‐Haur , Liu Shyun‐Yeu , Yang Jung‐Wu , Chiou Chang‐Ta , Chang Chi‐Hua , Chiang Wei‐Fan
Published: January 2018

Background

Oral verrucous hyperplasia is commonly observed in the oral cavity of betel quid chewers and is a potential malignant disorder. However, the prognostic factors and genetic alterations of oral verrucous hyperplasia are unclear.

Methods

We calculate the survival rate and prognostic factors using a Kaplan‐Meier analysis and Cox proportional hazards regression model. Copy number variations were analyzed using a single‐nucleotide polymorphism (SNP) array.

Results

The 5‐year disease‐free and cancer‐free survival rates of patients with oral verrucous hyperplasia were approximately 40% and 70%, respectively. Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions were risk factors for malignant transformation, whereas dysplasia did not affect outcomes. The gene amplification of CTTN, FOLR3, ORAOV1, PPFIA1, and RNF121 were associated with the poor prognosis of oral verrucous hyperplasia.

Conclusion

Heavy betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue lesions are high‐risk factors of patients with oral verrucous hyperplasia. The 5‐copy number variation‐associated genes could be used for early diagnosis and predicting the prognosis.
Viscosity—The weak link between Darcy's law and Richards' capillary flow
Authors: Germann Peter F.
Published: January 2018

Preferential flow, a term that includes macropore flow, non‐equilibrium flow, and finger flow, stands in well known conflict with Richards' () capillary flow. Acoustic velocity experiments demonstrate that preferential flow moves independently from, faster than, and before capillary flow during gravity‐driven infiltration. Viscous flow in permeable media is briefly introduced to the point where Richards' () particular treatment of viscosity turns out as the hydro‐mechanical bifurcation from general laminar flow. Preferential flow is expected during significant infiltration, however, spatio‐temporarily limited according to the viscous‐flow regime. Two ways of delineating capillary flow from viscous flow reveal minimum path widths of preferential flow in the range of about 20 μm.
Modelling the effect of changing precipitation inputs on deep soil water utilization
Authors: Qi Ji , Markewitz Daniel , Radcliffe David
Published: January 2018

Forests in the Southeastern United States are predicted to experience future changes in seasonal patterns of precipitation inputs as well as more variable precipitation events. These climate change‐induced alterations could increase drought and lower soil water availability. Drought could alter rooting patterns and increase the importance of deep roots that access subsurface water resources. To address plant response to drought in both deep rooting and soil water utilization as well as soil drainage, we utilize a throughfall reduction experiment in a loblolly pine plantation of the Southeastern United States to calibrate and validate a hydrological model. The model was accurately calibrated against field measured soil moisture data under ambient rainfall and validated using 30% throughfall reduction data. Using this model, we then tested these scenarios: (a) evenly reduced precipitation; (b) less precipitation in summer, more in winter; (c) same total amount of precipitation with less frequent but heavier storms; and (d) shallower rooting depth under the above 3 scenarios. When less precipitation was received, drainage decreased proportionally much faster than evapotranspiration implying plants will acquire water first to the detriment of drainage. When precipitation was reduced by more than 30%, plants relied on stored soil water to satisfy evapotranspiration suggesting 30% may be a threshold that if sustained over the long term would deplete plant available soil water. Under the third scenario, evapotranspiration and drainage decreased, whereas surface run‐off increased. Changes in root biomass measured before and 4 years after the throughfall reduction experiment were not detected among treatments. Model simulations, however, indicated gains in evapotranspiration with deeper roots under evenly reduced precipitation and seasonal precipitation redistribution scenarios but not when precipitation frequency was adjusted. Deep soil and deep rooting can provide an important buffer capacity when precipitation alone cannot satisfy the evapotranspirational demand of forests. How this buffering capacity will persist in the face of changing precipitation inputs, however, will depend less on seasonal redistribution than on the magnitude of reductions and changes in rainfall frequency.
Improving a distributed hydrological model using evapotranspiration‐related boundary conditions as additional constraints in a data‐scarce river basin
Authors: Wambura Frank Joseph , Dietrich Ottfried , Lischeid Gunnar
Published: January 2018

Many hydrological models have been calibrated and validated using hydrographs alone. Because streamflow integrates water fluxes in space, many distributed hydrological models tend to have multiple feasible descriptions of hydrological processes. This equifinality usually leads to substantial prediction uncertainty. In this study, additional constraints—namely, the spatial patterns of long‐term average evapotranspiration (ET), shallow groundwater level, and land cover change—were used to investigate the reduction of equifinality and prediction uncertainty in the Soil and Water Assessment Tool (SWAT) in the Wami River basin in Tanzania. The additional constraints were used in the set‐up, parameter emulation and calibration of the SWAT model termed an improved hydrological model (IHM). The IHM was then compared with a classical hydrological model (CHM) that was also developed using the SWAT model but without additional constraints. In the calibration, the CHM used only the hydrograph, but the IHM used the hydrograph and the spatial pattern of long‐term average ET as an additional constraint. The IHM produced a single, unique behavioural simulation, whereas the CHM produced many behavioural simulations that resulted in prediction uncertainty. The performance of the IHM with respect to the hydrograph was more consistent than that of the CHM, and the former clearly captured the mean behaviour of ET in the river basin. Therefore, we conclude that additional constraints substantially reduce equifinality and prediction uncertainty in a distributed hydrological model.
Prognostic significance of tumor‐infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: A large‐scale cohort study
Authors: Wang Ya‐Qin , Chen Yu‐Pei , Zhang Yu , Jiang Wei , Liu Na , Yun Jing‐Ping , Sun Ying , He Qing‐Mei , Tang Xin‐Ran , Wen Xin , Yang Xiao‐Jing , Zhang Pan‐Pan , Zhang Jian , Lei Yuan , Li Ying‐Qin , Ma Jun
Published: January 2018

The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor‐infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease‐free survival (DFS) for patients with nondisseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28–0.58,p < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27–0.64,p < 0.001), distant metastasis‐free survival (DMFS, HR 0.37, 95% CI 0.23–0.58,p < 0.001) and local‐regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25–0.73,p = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker.
Food Security by Optimal Use of Water: Synthesis of the 6th and 7th World Water Forums and Developments since Then
Authors: Steduto Pasquale , Schultz Bart , Unver Olcay , Ota Shinsuke , Vallee Domitille , Kulkarni Suresh , Dagnino‐Johns Garcia Macarena
Published: January 2018

The world's population is expected to grow from 7.4 billion at present to 10.0 billion by 2055. Combined with the expected rise in living standards, urbanization and growing demands for animal feed and energy from crops, this requires a substantial increase in cereal production to ensure sustainable food security at affordable prices. Overall, global cereal production meets current demand and the global cereal stock is stable. Achieving the required increase in cereal production seems to be possible. The contributors to the Theme Contribute to Food Security by Optimal Use of Water of the 6th World Water Forum (WWF6) identified nine targets that address the relevant aspects. They reviewed existing and future needs, as well as existing and potential solutions to reach the targets. The contributors to the Theme Water for Food of the 7th World Water Forum (WWF7) elaborated on this work and focused more on the progress so far as well as on issues related to implementation, and formulated a goal and eight objectives to be achieved.

This paper presents a summarized overview of key issues, findings, targets, objectives, solutions and recommendations of WWF6 and WWF7 with respect to water for food, while taking into account developments since then and updated data. Copyright © 2018 John Wiley & Sons, Ltd.
On secrecy performance of industrial Internet of things
Authors: Jameel Furqan , Javed Muhammad A. , Jayakody Dushantha N.K. , Hassan Syed A.
Published: January 2018

Physical layer security has been shown to hold promise as a new paradigm for securing wireless links. This paper provides secrecy performance analysis for industrial Internet of things, where a set of industrial devices communicates in the presence of eavesdropper under a Weibull fading environment. We derive a closed‐form expression for secrecy outage probability and evaluate the secrecy performance for the device selection scheme. This scheme is then compared with a benchmark technique, namely, a uniform selection scheme to quantify the performance improvements. In order to investigate the impact of Weibull shape parameter on secrecy performance, the derived expressions are used to perform a generalized diversity order analysis for both schemes. Finally, secrecy analysis conditioned on successful transmission of message is provided and analytical expression is derived. Extensive simulations are performed to validate the accuracy of the derived analytical expressions.
Identification of microRNAs as potential markers of ovarian toxicity
Authors: Furlong Hayley C. , Stämpfli Martin R. , Gannon Anne M. , Foster Warren G.
Published: January 2018

Exposure to environmental toxicants has been associated with ovarian dysfunction yet sensitive biomarkers of adverse effect are lacking. We previously demonstrated that cigarette smoke exposure induced decreased relative ovarian weight, increased follicle loss and granulosa cell autophagy in mice. We postulate that cigarette smoke exposure will induce changes in the epigenome that can be used to reveal potential sensitive biomarkers of ovarian toxicity. Therefore, we evaluated differences in expression of 940 microRNAs (miRNAs), environmentally responsive small non‐coding genes that regulate expression of genes at the post‐transcriptional level, in ovarian tissue from 8‐week‐old female C57BL/6 mice exposed to room air or cigarette smoke 5 days per week for 8 weeks. A total of 152 miRNAs were dysregulated in expression, 17 of which were examined with quantitative polymerase chain reaction analysis. Using an online miRNA database tool, complete lists of predicted miRNA gene targets were generated, 12 of which were measured for their expression levels with quantitative polymerase chain reaction. An online bioinformatics resource database, DAVID generated functional classification lists of the target genes and their associated biological pathways. Results of the present pilot study suggest that miR‐379, miR‐15b, miR‐691, miR‐872 and miR‐1897‐5p are potentially useful markers of ovarian toxicity and dysfunction. Examination of the expression pattern of the target mRNA for these miRNA species demonstrated that cigarette smoke exposure induced significant changes that affect mitogen‐activated protein kinase signaling pathways. We therefore suggest that miRNAs could serve as sensitive markers of ovarian toxicity and elucidate affected pathways.
Effect of titanium ions on the Hippo/YAP signaling pathway in regulating biological behaviors of MC3T3‐E1 osteoblasts
Authors: Zhu Wen‐qing , Ming Pan‐pan , Qiu Jing , Shao Shui‐yi , Yu Ying‐juan , Chen Jia‐xi , Yang Jie , Xu Li‐na , Zhang Song‐mei , Tang Chun‐bo
Published: January 2018

Titanium (Ti) and its corresponding alloys have been widely applied in dental and orthopedic implants. Owing to abrasion and corrosion of implants in the unfavorable electrolytic aqueous environment of the host body, Ti ions could be released from implants and accumulated in local tissues. Recent studies have found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues and subsequently influenced long‐term effects on implant prostheses. However, the potential molecular mechanisms underlying the damage to osteoblasts induced by Ti ions remained unclear. Hippo signaling has been confirmed to be involved in organ size and tissue regeneration in many organs, while its roles in osteoblasts differentiation and bone repair remained elusive. Therefore, we hypothesize that YAP, a regulator of Hippo pathway, inhibited osteoblast growth, skeletal development and bone repair, as well as excessive Ti ions promoted the progression of YAP activation. This study aimed to explore the role of Hippo/YAP signaling pathway in the biotoxicity effect of Ti ions on osteoblast behaviors. Here, we confirmed that 10 ppm Ti ions, a minimum concentration gradient previously reported that was capable of suppressing osteoblasts growth, induced nuclear expression of YAP in osteoblasts in our study. Furthermore, 10 ppm Ti ion‐induced YAP activation was found to downregulate osteogenic differentiation of MC3T3‐E1 cells. Most importantly, the hypothesis we proposed that knockdown of YAP did reverse the inhibitory effect of 10 ppm Ti ions on osteogenesis has been verified. Taken together, our work provides insights into the mechanism of which YAP is involved in regulating osteoblast behaviors under the effect of Ti ions, which may help to develop therapeutic applications for Ti implant failures and peri‐implantitis.
Mesoporous bioactive glass embedding propolis and cranberry antibiofilm compounds
Authors: Galarraga‐Vinueza Maria Elisa , Mesquita‐Guimarães Joana , Magini Ricardo S. , Souza Júlio C. M. , Fredel Marcio C. , Boccaccini Aldo R.
Published: January 2018

The aim of this study was to evaluate the chemical reactivity of 58S mesoporous bioactive glass (MBG) particles in as‐synthesized condition and after embedding propolis and cranberry antibiofilm compounds at different concentrations. MBG 58S was synthesized by alkali sol‐gel method with the addition of the triblock pluronic copolymer P123 as surfactant. Samples were characterized by physicochemical properties measurement, N2 adsorption/desorption analysis, and field emission gun scanning electron microscopy (FEGSEM) observations. MBG powders were immersed into 5 and 10 µg/mL propolis or cranberry solutions for 24 h. The chemical reactivity of the specimens was evaluated by FEGSEM, EDX, FTIR, Ca/P ratio, XRD, and sample weight gain analysis after being immersed in simulated body fluid (SBF) for 8, 24, and 72 h. MBG particles exhibited the expected chemical composition with a particle size distribution ranging from 1.44 to 955 µm, and a mean particle size of 154 µm. MBG particles exhibited a pore volume of 0.8 cc/g, pore radius of ∼2 nm, and surface area of 350.2 m2/g, according to BJH and BET analyses. A hydroxyl‐carbonate apatite (HCAp) layer was formed on all samples after SBF immersion for 72 h. Pure MBG showed the highest chemical reactivity after 72 h, with the resulting apatite layer exhibiting a Ca/P ratio of ∼1.6 in accordance to stoichiometric biological apatite. MBG embedding propolis and cranberry can be considered for future microbiological analysis since the presence of propolis or cranberry did not interfere with MBG's ability to develop a HCAp layer, which is an essential feature for bone regeneration applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1614–1625, 2018.
Retracted: microRNA‐129‐5p involved in the neuroprotective effect of dexmedetomidine on hypoxic‐ischemic brain injury by targeting COL3A1 through the Wnt/β‐catenin signaling pathway in neonatal rats
Authors: Zhou Xiu‐Min , Liu Jie , Wang Ying , Zhang Shu‐Li , Zhao Xin , Xu Xiang , Pei Jian , Zhang Man‐He
Published: January 2018

Our study aims to elucidate the mechanisms how microRNA‐129‐5p (miR‐129‐5p) involved in the neuroprotective effect of dexmedetomidine (DEX) on hypoxic‐ischemic brain injury (HIBI) by targeting the type III procollagen gene (COL3A1) through the Wnt/β‐catenin signaling pathway in neonatal rats. A total of 120 rats were obtained, among which 15 rats were selected as sham group and rest rats as model, DEX, DEX + negative control (DEX + NC), DEX + miR‐129‐5p mimics, DEX + miR‐129‐5p inhibitors, DEX + XAV‐939, and DEX + miR‐129‐5p inhibitors + XAV‐939 groups. A dual‐luciferase reporter assay was performed for the target relationship between miR‐129‐5p and COL3A1. Weight rate and water content of cerebral hemisphere were detected. Quantitative real‐time polymerase chain reaction and Western blot analysis were conducted to detect miR‐129‐5p expression and expressions of COL3A1, E‐cadherin, T‐cell factor (TCF)− 4, and β‐catenin. The DEX, DEX + miR‐129‐5p mimics, DEX + XAV‐939 groups had increased weight rate of the cerebral hemisphere, but decreased water content of left cerebral hemisphere, levels of COL3A1, β‐catenin, TCF‐4, and E‐cadherin in the hippocampus compared with the model and DEX + miR‐129‐5p inhibitors groups. COL3A1 was verified as the target gene of the miR‐129‐5p. Compared with the DEX + NC and DEX + miR‐129‐5p inhibitors + XAV‐939 groups, the DEX + XAV‐939 and DEX + miR‐129‐5p mimics groups had elevated weight rate of the cerebral hemisphere, but reduced water content of left cerebral hemisphere, levels of COL3A1, β‐catenin, TCF‐4, and E‐cadherin in the hippocampus. Our findings demonstrate that miR‐129‐5p improves the neuroprotective role of DEX in HIBI by targeting COL3A1 through the Wnt/β‐catenin signaling pathway in neonatal rats.
LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA through HIF‐1α/VEGF signaling in ischemic stroke
Authors: Zhang Lin , Luo Xianliang , Chen Feng , Yuan Wei , Xiao Xinli , Zhang Xiaohua , Dong Yaru , Zhang Yuanxiao , Liu Yong
Published: January 2018

Studies have shown that long noncoding ribonucleic acids (lncRNAs) play critical roles in multiple biologic processes. However, the Small Nucleolar RNA Host Gene 1 (SNHG1) function and underlying molecular mechanisms in ischemic stroke have not yet been reported. In the present study, we found that SNHG1 expression was remarkably increased both in isolated cerebral micro‐vessels of a middle cerebral artery occlusion (MCAO) mice model, and in oxygen‐glucose deprivation (OGD)‐cultured mice brain micro‐vascular endothelial cells (BMECs), meanwhile, the SNHG1 level was negatively correlated with miR‐18a in MCAO mice. Mechanistically, SNHG1 inhibition presents larger brain infarct size and worsens neurological scores in MCAO mice. Consistent with the in vivo findings, SNHG1 inhibition also significantly increased caspase‐3 activity and cell apoptosis in OGD‐cultured BMECs. Furthermore, we found that SNHG1 functions as a competing endogenous RNA (ceRNA) for miR‐18a, thereby regulating the de‐repression of its endogenous target HIF‐1α and promoting BMEC survival through HIF‐1α/VEGF signaling. This study found a neuroprotective effect of SNHG1 mediated by HIF‐1α/VEGF signaling through acting as a ceRNA for miR‐18a. These findings reveal a novel function of SNHG1, which contributes to an extensive understanding of ischemic stroke and provides novel therapeutic options for this disease.
The exosomes released from different cell types and their effects in wound healing
Authors: Golchin Ali , Hosseinzadeh Simzar , Ardeshirylajimi Abdolreza
Published: January 2018

Despite important advances in regenerative medicine and tissue engineering, still, wound healing remains a challenging clinical problem. Cell therapy has opened a new viewpoint in medicine as well as wound management, although it has some limitations. On the other hand, there are some hopes for the eliminated of cellular therapies limitations by “exosomes.” The term “exosome” has been frequently used to describe all vesicles released by different cells into the extracellular environment and can influence tissue responses to injury, infection, immune system, and healing. Exosomes contain cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs that have been found in some body fluids and can be transferred between cells to mediating cell‐to‐cell communication and interactions. Recently, several studies have demonstrated that exosomes are one of the key secretory products of various cell type especially mesenchymal stem cells (MSCs) to regulate many biological processes such wound healing. Hence, understanding these exosomes effects may help to improve wound management and highlight a new therapeutic model for cell‐free therapies with decreased side effects for the wound repair.
Pretreatment of glial cell‐derived neurotrophic factor and geranylgeranylacetone ameliorates brain injury in Parkinson's disease by its anti‐apoptotic and anti‐oxidative property
Authors: Yue Peijian , Gao Lin , Wang Xuejing , Ding Xuebing , Teng Junfang
Published: January 2018

The aim of the present study was to determine the combined effects of glial cell‐derived neurotrophic factor (GDNF) and geranylgeranylacetone (GGA) on neuron apoptosis and oxidative stress in Parkinson's disease (PD). A mouse MPTP model of PD and cellular models of H2O2 and MPP+‐treated PC12 cells were established. Swimming, pole, and traction tests were used to detect behavioral impairment. Tyrosine hydroxylase (TH) immunohistochemistry was used to evaluate the neuron loss. TUNEL and flow cytometer method were used to identify the neuron apoptosis. MDA levels and activities of antioxidant enzymes were used to detect the oxidative damage. The PD model of mice received GDNF and GGA exhibited a significant recovery in their swim, pole, and traction scores. Moreover, the combined treatment significantly reduced the neuron apoptosis in the substantia nigra (SN) of PD mice or in H2O2 or MPP+‐induced PC12 cells compared with the single drug group. In addition, significant reduction of MDA levels and improvement of activities of CAT, SOD, and GSH‐px were observed after GDNF and GGA treatment in the PD model and H2O2 or MPP+‐induced PC12 cells. The combination of GDNF and GGA ameliorated neural apoptosis and oxidative damage in PD.
Glycosylated CD147 reduces myocardial collagen cross‐linking in cardiac hypertrophy
Authors: Ru Ning‐Yu , Cui Long‐Biao , Jiao Bo , Zhang Lin , Jiang Shuai , Yu Zhi‐Bin
Published: January 2018

The mechanism of transition from chronic pressure overload‐induced cardiac hypertrophy to heart failure is still unclear. Angiotensin II (Ang II) may be an important factor that mediates the transition in the end‐stage of cardiac hypertrophy. In the present study, Goldblatt two‐kidney one‐clip (2K1C) rat model was used to simulate Ang II‐induced hypertension. The elevated Ang II not only induced the concentric hypertrophy of left ventricle and cardiac fibrosis, but also increased the expression and glycosylation of CD147 in 2K1C rats. The left ventricular structure and function detected by echocardiogram showed a sign of the transition from cardiac hypertrophy to heart failure in 16 weeks of 2K1C rats. Ang II can activate N‐acetylglucosamine transferase V (GnT‐V), a key enzyme for CD147 glycosylation. Retinoic acid, an agonist of GnT‐V, further increased glycosylated CD147, and activated matrix metalloproteinase‐2/‐9 (MMP‐2 and MMP‐9) in the hypertrophied left ventricle of 2K1C rat. Meanwhile, collagen cross‐linking in the hypertrophied left ventricle significantly reduced in 2K1C rats. On the contrary, tunicamycin, an inhibitor of N‐glycan biosynthesis, inhibited glycosylation of CD147 and activity of MMP‐2 and MMP‐9, and then maintained a stable of collagen cross‐linking in the 2K1C rat hearts. The above results suggested that Ang II increased glycosylated CD147 which activated MMP‐2 and MMP‐9. Collagens were degraded by the activated MMPs and then reduced collagen cross‐linking. Finally, the hypertrophied left ventricle was progressively dilated in chronic pressure overload due to losing the limitation of collagen cross‐linking. Therefore, the compensated hypertrophy of left ventricle gradually transited to congestive heart failure.
The α1‐adrenergic receptor is involved in hepcidin upregulation induced by adrenaline and norepinephrine via the STAT3 pathway
Authors: Kong Wei‐Na , Cui Yanmei , Fu Yu‐Jian , Lei Yuhua , Ci Yunzhe , Bao Yongping , Zhao Shuqiang , Xie Lide , Chang Yan‐Zhong , Zhao Shu‐E
Published: January 2018

Elevated body iron stores are associated with hypertension progression, while hypertension is associated with elevated plasma catecholamine levels in patients. However, there is a gap in our understanding of the connection between catecholamines and iron regulation. Hepcidin is a key iron‐regulatory hormone, which maintains body iron balance. In the present study, we investigated the effects of adrenaline (AD) and norepinephrine (NE) on hepatic hepcidin regulation. Mice were treated with AD, NE, phenylephrine (PE, α1‐adrenergic receptor agonist), prazosin (PZ, α1‐adrenergic receptor antagonist), and/or propranolol (Pro, β‐adrenergic receptor antagonist). The levels of hepcidin, as well as signal transducer and activator of transcription 3 (STAT3), ferroportin 1 (FPN1), and ferritin‐light (Ft‐L) protein in the liver or spleen, were assessed. Six hours after AD, NE, or PE treatment, hepatic hepcidin mRNA levels increased. Pretreatment with PZ, but not Pro, abolished the effects of AD or NE on STAT3 phosphorylation and hepatic hepcidin expression. When mice were treated with AD or NE continuously for 7 days, an increase in hepatic hepcidin mRNA levels and serum hepcidin concentration was also observed. Meanwhile, the expected downstream effects of elevated hepcidin, namely decreased FPN1 expression and increased Ft‐L protein and non‐heme iron concentrations in the spleen, were observed after the continuous AD or NE treatments. Taken together, we found that AD or NE increase hepatic hepcidin expression via the α1‐adrenergic receptor and STAT3 pathways in mice. The elevated hepatic hepcidin decreased FPN1 levels in the spleen, likely causing the increased iron accumulation in the spleen.
Retracted: Ginsenoside Rh2 inhibits proliferation and migration of medulloblastoma Daoy by down‐regulation of microRNA‐31
Authors: Chen Yan , Shang Hong , Zhang Shunli , Zhang Xiaohong
Published: January 2018

This study aimed to investigate the effects of ginsenoside Rh2 on proliferation, apoptosis, and migration of the human medulloblastoma cell line Daoy, as well as to explore the potential mechanisms of the effects. The human medulloblastoma cell line Daoy was cultured in vitro and treated with or without ginsenoside Rh2. CCK‐8 assay was performed to investigate the effect of Rh2 on cell survival using a cell counting Kit‐8. Cell proliferation was assessed by BrdU assay. Cell apoptosis was determined using flow cytometry analysis. Cell migration was detected using a modified two‐chamber migration assay. MiR‐31 mimic and the NC control were transfected into Daoy cells and detected by qRT‐PCR. The expression of Wnt3a, Wnt5a, and β‐catein was detected by Western blot analysis. Rh2 efficiently suppressed the proliferation and migration, and promoted the apoptosis of Daoy cells. Additionally, Rh2 could down‐regulate miR‐31. miR‐31 overexpression reversed the effects of Rh2 on proliferation, apoptosis and migration of Daoy cells, and activated the Wnt/β‐catein signaling pathways in Daoy cells. Rh2 could inhibit the proliferation and migration, and induce apoptosis of Daoy medulloblastoma cells through down‐regulation of miR‐31 to inactivate the Wnt/β‐catein signaling pathway. Therefore, Rh2 may have a utility in clinical applications for the treatment of medulloblastoma.
ER stress mediated regulation of miR23a confer Hela cells better adaptability to utilize glycolytic pathway
Authors: Poyyakkara Aswini , Raji Grace R. , Kunhiraman Haritha , Edatt Lincy , Kumar Sameer V.B.
Published: January 2018

Cancer cells exhibit increased dependency on aerobic glycolysis, a phenomenon referred as the “Warburg effect” and therefore, blocking glycolysis by using non‐metabolizable analogues of glucose, like 2‐Deoxy glucose (2‐DG), has been proposed to be of huge therapeutic importance. One of the major drawbacks of using 2‐DG as a chemotherapeutic agent is that it can induce ER stress. ER stress is a hall mark in many solid tumors and the unfolded protein response (UPR) associated with it initiates many survival mechanisms in cancer cells. In the present study, we report a novel survival mechanism associated with ER stress, by which the cancer cells become more adapted to aerobic glycolysis. When ER stress was induced in Hela cells by treating them with 2‐DG or Thapsigargin (TG) the expression and activity of LDH was significantly up regulated, conferring the cells a greater glycolytic potential. A simultaneous decrease was observed in the expression of miR‐23a, which was predicted in silico to have target site on the 3′UTR of LDH A and B mRNAs. miRNA over expression studies and mRNA degradation assays suggest that miR‐23a could target LDH A and LDH B mRNAs. Further on the basis of our results and previous scientific reports, we propose that “c‐Myc,” which is over expressed during ER stress, repress the expression of miR‐23a, which in turn regulates the expression of its target genes viz., LDH A and LDH B, thereby making the cells more competent to survive in tumor microenvironment, which requires efficient use of aerobic glycolysis.
Regulation of human trophoblast cell syncytialization by transcription factors STAT5B and NR4A3
Authors: Kusama Kazuya , Bai Rulan , Imakawa Kazuhiko
Published: January 2018

In human trophoblast cells, cyclic AMP or its inducer forskolin (FSK) activates two downstream signaling molecules, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC), both of which induce syncytialization, cell fusion, and the production of human chorionic gonadotropin (hCG) and progesterone. However, a transcription factor other than GCM1 and molecular mechanisms associated with these events have not been well characterized. To identify novel transcription factors involved in syncytialization of cAMP‐stimulated human choriocarcinoma BeWo cells, the microarray analysis was performed with RNAs extracted from PKA‐ or EPAC‐selective cAMP analog‐stimulated BeWo cells, from which two up‐regulated transcription factors, STAT5 and NR4A3, were found. The knockdown of STAT5B decreased FSK‐induced cell fusion and the expression of syncytialization markers, CGB, syncytin1, syncytin2, GCM1, and OVOL1, but NR4A3 knockdown increased FSK‐induced cell fusion and the expression of CGB and syncytin2. These findings indicated that cAMP‐PKA up‐regulated STAT5B, followed by increase in syncytin2 expression through GCM1 and OVOL1, resulting in cell fusion and hCG production, while cAMP‐PKA‐up‐regulated NR4A3 could decrease syncytin2 expression, and suggested that both positive and negative effects of STAT5B and NR4A3, respectively, are required to control the degree of syncytialization in human trophoblast cells.
Calbindin‐D28K mediates 25(OH)D3/VDR‐regulated bone formation through MMP13 and DMP1
Authors: Yang Li‐Ping , Dong Ya‐Ping , Luo Wen‐Ting , Zhu Tong , Li Qi‐Wei , Zhang Li‐Jun , Kong Juan , Yuan Zheng‐Wei , Zhao Qun
Published: January 2018

Calcium binding protein calbindin‐D28K (CaBP28K) mediates the relationship between vitamin D and calcium, but its mechanism remains unclear during bone formation. The present study reports that maternal CaBP28K levels were positively correlated with paired umbilical cord CaBP28K levels. In addition, CaBP28K levels were positively correlated with the body length, and head and chest circumferences of neonates, but negatively correlated with maternal 25(OH)D3 levels. CaBP28K was also downregulated in MC3T3‐E1 osteoblasts when treated with 1,25(OH)2D or VDR overexpression, but was upregulated in the femur of 1α(OH)ase(−/−) mice. Furthermore, it was found CaBP28K may influence cell differentiation and matrix formation through the regulation of DMP1 and the interaction with MMP13 in osteoblasts. This suggests that CaBP28K could be a candidate for the negative role of 1,25(OH)2D/VDR in regulating bone mass.
Relationships between Dicer 1 polymorphism and expression levels in the etiopathogenesis of preeclampsia
Authors: Eskandari Fatemeh , Teimoori Batool , Rezaei Mahnaz , Mohammadpour‐Gharehbagh Abbas , Narooei‐Nejad Mehrnaz , Mehrabani Mehrnaz , Salimi Saeedeh
Published: January 2018

Preeclampsia (PE) is a pregnancy‐specific complication which is a major cause of maternal and fetal morbidity and mortality. Recent studies have shown the aberrant expression of microRNAs (miRNAs) in the placenta of patients with PE. Dicer1 is a key enzyme in the generation of small noncoding RNAs including miRNAs. The aim of this study is to investigate the relationship between maternal and placental Dicer1 rs3742330 polymorphism and placental Dicer1 mRNA expression in PE and normotensive pregnant women. The blood and placenta of PE pregnant and normotensive pregnant women were collected after delivery. Dicer1 rs3742330 polymorphism was genotyped using PCR‐RFLP method. The mRNA expression levels were measured using quantitative real time PCR. The maternal Dicer1 rs3742330 polymorphism was not associated with PE or PE severity; however, the placental Dicer1 rs3742330 AG genotype was associated with two fold higher risk of PE and three fold higher risk of severe PE (P = 0.018 and P = 0.005, respectively). The relative mRNA expression of Dicer1 gene in the placenta did not differ between the two groups. In addition, the relative mRNA expression of Dicer1 gene was significantly lower in the placenta of women with rs3742330 AG+GG genotypes in the total population (P = 0.028) and PE women (P = 0.004), but not in the control group. In conclusion, there was a relationship between placental but not maternal Dicer1 rs3742330 polymorphism and PE. There was no difference in Dicer1 mRNA expression between the PE and control groups; however, it was significantly lower in the placenta of women with rs3742330 AG+GG genotypes.