bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia‐induced microRNA‐26b inhibition contributes to hypoxic pulmonary hypertension via CTGF
Authors: Zhou Sijing , Sun Li , Cao Chao , Wu Peipei , Li Min , Sun Gengyun , Fei Guanghe , Ding Xing , Wang Ran 
Published: August 2017

AbstractThe objective of this study was to explore the role of miRNAs in the control of HPH as well as molecular mechanism underlying. Computational analysis and luciferase assay were carried out to search the target gene of miR‐26b. Luciferase assay, RT‐PCR and western‐blot analysis was performed to test interaction among hypoxia, miR‐26b, SRF and CTGF. MiR‐26b was significantly downregulated; meanwhile, CTGF and SRF were significantly upregulated in HPH rat model. Using computational analysis, CTGF was found to be a virtual target gene of miR‐26b, and only cell transfected with vectors containing wild‐type CTGF 3′UTR and miR‐26b showed a lower luciferase activity than scramble control. Hypoxia significantly inhibited miR‐26b promoter, and promoted SRF promoter. Meanwhile, hypoxia had no effect on CTGF promoter. In addition, SRF promoted the promoter of CTGF. MiR‐26b was significantly downregulated; meanwhile, CTGF and SRF were upregulated in PASMCs exposed to hypoxia. In addition, miR‐26b and SRF siRNA, but not CTGF siRNA, significantly inhibited SRF expression. Meanwhile, miR‐26b, SRF siRNA, and CTGF siRNA significantly inhibited CTGF expression in hypoxia‐treated cell. PASMCs treated with hypoxia showed higher cell viability and higher percentage cells in S phase than the control, which could be reversed by miR‐26b, SRF siRNA, and CTGF siRNA transfection. These findings suggested that hypoxia induced miR‐26b inhibition and SRF and CTGF upregulation in HPH rat model. CTGF mediated hypoxia‐induced regulation of miR‐26b and SRF in proliferation of PASMCs, which indicated that hypoxia‐induced miR‐26b inhibition contributed to the pathogenesis of HPH via CTGF.
The N‐terminal ubiquitin‐associated domain of Cezanne is crucial for its function to suppress NF‐κB pathway
Authors: Ji Yanxi , Cao Liu , Zeng Lanyi , Zhang Zhen , Xiao Qiaoqiao , Guan Penglin , Chen Shiyou , Chen Yu , Wang Min , Guo Deyin 
Published: August 2017

AbstractCezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF‐κB to attenuate NF‐κB activation and to restrain pro‐inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11‐linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build‐up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1. However, how is Cezanne recognized and recruited to TNFR complex is not clear yet. In this study, we characterized a ubiquitin‐associated (UBA) domain in the N‐terminal region of Cezanne and proved its activity to bind Lys63 polyubiquitin chain. By constructing a series of truncated and site‐specific point mutants, we further localized the crucial binding sites for Lys63 polyubiquitin chains at Leu9 and Ser10 sites of Cezanne UBA domain. Mutation at these sites disrupted the recruitment of Cezanne to activated TNFR complex and dramatically reduced the inhibition of NF‐κB activation by Cezanne. Our study demonstrated that the N‐terminal UBA domain is crucial for the function of Cezanne during NF‐κB activation. Cezanne is recognized and recruited into activated TNFR complex by specifically binding to polyubiquitinated signaling proteins after TNF stimulation through its N‐terminal polyubiquitin binding site. This study sheds light on the molecular mechanism of negative regulation of NF‐κB activation by Cezanne.
Loureirin B promotes insulin secretion through inhibition of KATP channel and influx of intracellular calcium
Authors: Sha Yijie , Zhang Yuelin , Cao Jing , Qian Kai , Niu Bing , Chen Qin 
Published: August 2017

AbstractThe development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For searching the promotion of insulin secretion with the treatment of loureirin B, experiments were employed based on cell experiments and computational methods. First, promotion of insulin secretion was dependent on extracellular glucose concentration. At the genetic level, loureirin B enhanced the relative mRNA level of Pdx‐1 and MafA. Meanwhile the intracellular level of ATP increased due to the continuous absorption of glucose. Further experiments showed that the currents of KATP channel on Ins‐1 cells were inhibited and the voltage‐dependent calcium channels were subsequently activated. The increase of Cx43 protein expression might mediate the Ca2+ to the intracellular. Through computational simulation, we hypothesized that loureirin B might interact with KATP channels to promote insulin secretion. In conclusion, it could be concluded that loureirin B promoted insulin secretion mainly through increasing mRNA level of Pdx‐1, MafA, intracellular ATP level, inhibiting the KATP current, influx of Ca2+ to the intracellular.
Safety, Tolerability, and Pharmacokinetic Characteristics of a Novel Nonopioid Analgesic, VVZ‐149 Injections in Healthy Volunteers: A First‐in‐Class, First‐in‐Human Study
Authors: Oh Jaeseong , Lee SeungHwan , Kim Anhye , Yoon Jangsoo , Jang Kyungho , Lee Doo H. , Cho Sunyoung , Lee Sang Rim , Yu Kyung‐Sang , Chung Jae‐Yong 
Published: August 2017

AbstractVVZ‐149, a dual antagonist of GlyT2 and 5HT2A receptors, is an investigational analgesic with a novel mechanism of action that is currently under early‐stage clinical development as an injectable agent for the treatment of postoperative pain. Here, the safety, tolerability, and pharmacokinetics of VVZ‐149 injections in healthy male volunteers were explored in a randomized, double‐blind, single‐ and multiple‐ascending‐dose (SAD and MAD, respectively), placebo‐controlled clinical study. Subjects randomly received a 4‐hour intravenous infusion of 0.25‐8 mg/kg VVZ‐149 or placebo in the SAD study (n = 46) or a 4‐hour intravenous infusion of 4–7 mg/kg VVZ‐149 or placebo twice daily for 3 days in the MAD study (n = 20). Serial blood and urine samples were collected for the pharmacokinetic analysis of VVZ‐149 and its active metabolite (VVZ‐368). Noncompartmental and compartmental pharmacokinetic analyses were performed. Various dosing scenarios were simulated to identify the adequate dosing regimen for the subsequent trials. Plasma exposure to VVZ‐149 and VVZ‐368 showed a dose‐proportional increase. VVZ‐149 did not accumulate in the plasma, whereas the plasma concentration of VVZ‐368 increased by 1.23‐ to 2.49‐fold after the fifth and sixth doses, respectively, in the MAD trial. Among the simulated dosing regimens, a loading dose followed by a maintenance dose was found to be an optimal dosing regimen, yielding the effective concentration estimated from animal studies in rat models of neuropathic or inflammatory pain. Single‐ or multiple‐dose administration of VVZ‐149 was generally well tolerated. These results showed that 0.5–8 mg/kg VVZ‐149 exhibited linear pharmacokinetic characteristics and can be safely administered in further clinical studies.
The structure and ultrastructure of the egg capsules of stoneflies of the genusIsoperla(Insecta, Plecoptera, Perlodidae)
Authors: Michalik Anna , Miliša Marko , Michalik Katarzyna , Rościszewska Elżbieta 
Published: August 2017

AbstractThe egg capsules of five systellognathan stoneflies species representing the genusIsoperla(Plecoptera, Perlodidae) have been investigated using light and electron microscopes (SEM and TEM). We consider the structural modifications of egg coverings (egg capsules, eggshells) like: a shape of a capsule, presence of structures fixing an egg to the substratum under water, intrachorionic aeropylar system facilitating gas exchange as a factor adapting an egg/embryo to the environment. The structures protecting eggs against desiccation during a female flight before oviposition into water as well as against the dangers of external mechanical injury caused by turbulences in rapid water currents of mountain streams are described and discussed. The ground plan of the egg capsule in arctoperlarian stoneflies is also discussed.
A stereovision model applied in bio‐micromanipulation system based on stereo light microscope
Authors: Wang Yuezong 
Published: August 2017

AbstractA bio‐micromanipulation system is designed for manipulating micro‐objects with a length scale of tens or hundreds of microns based on stereo light microscope. The world coordinate reconstruction of points on the surface of micro‐objects is an important goal for the micromanipulation. Traditional pinhole camera model is applied widely in macrocomputer vision. However, this model will output bad data with remarkable error if it is directly used to reconstruct three‐dimensional world coordinates for stereo light microscope. Therefore, a novel and improved pinhole camera model applied in bio‐micromanipulation system is proposed in this article. The new model is composed of binocular‐pinhole model and error‐correction model. The binocular‐pinhole model is used to output the basic world coordinates. The error‐correction model is used to correct the errors from the basic world coordinates and outputs the final high‐precision world coordinates. The results show that the new model achieves a precision of 0.01 mm in the X direction, 0.01 mm in the Y direction, and 0.015 mm in the Z direction within a maximum reconstruction distance of 4.1 mm in the X direction, 2.9 mm in the Y direction, and 2.25 mm in the Z direction, and that traditional pinhole camera model achieves a lower and unsatisfactory precision of about 0.1 mm.
Who gets the benefit of the doubt? The impact of causal reasoning depth on how violations of gender stereotypes are evaluated
Authors: Keck Steffen , Babcock Linda 
Published: August 2017

SummaryA large body of research demonstrates that women encounter severe penalties for violating gender stereotypes. In this paper, we explore the conditions under which the reverse is true—when being subject to a stereotype can actually benefit a woman compared to a man who is not subject to the same stereotype. In particular, we suggest that in situations of causal ambiguity—uncertainty about the reasons that a behavior occurred—differences in how men and women are evaluated will be moderated by the extent to which observers engage in a low or a high level of deliberative causal reasoning. In 3 experimental studies, participants were asked to make judgments about an employee who violated a female gender stereotype by failing to provide help to a coworker when asked to do so, but the reasons for this behavior were unclear. When participants were prompted to engage in deliberative causal reasoning, women were evaluated more positively than men, but not in the absence of such a prompt. Moreover, when participants did engage in deliberative causal reasoning, the more positive evaluations of women compared to men were driven by participants' beliefs that women's behavior was due more to situational constraints than the same behavior by men.
Frequency, duration and severity of drought in the Semiarid Northeast Brazil region
Authors: Brito S. S. B. , Cunha A. P. M. A. , Cunningham C. C. , Alvalá R. C. , Marengo J. A. , Carvalho M. A. 
Published: August 2017

ABSTRACTDrought is the natural disaster that impacts the greatest number of people and produces the most significant economic losses. This work presents a quantitative assessment of drought events occurred in the Semiarid region of Northeast Brazil during 1981–2016. The purpose of this study is to provide an overview of drought intensity for the last 36 years, analysing their severity, frequency and duration, considering hydro‐meteorological and agricultural aspects. To evaluate these two aspects, the 12‐month standardized precipitation index and the vegetation health index were considered to investigate drought characteristics. The definition of drought event for both these indices was performed regarding start and end month. In this context, drought duration is considered equal to the number of months of event, drought frequency is the number of events per time period and the drought severity is the absolute value of integral area below zero. Results show that the most severe and prolonged drought occurred in 2011–2016. In a clear contrast to previous droughts in past decades, during these last 5‐years period drought were more frequent, severe and affected a larger area with significant impacts for population, as well as economical activities.
An improved model for malaria pigment and β‐hematin: Fe(OEP)picrate
Authors: Puntharod Ratchadaporn , Haller Kenneth J. , Robertson Evan G. , Gwee Eunice S. H. , Izgorodina Ekaterina I. , Wood Bayden R. 
Published: August 2017

Synthesis and crystallographic and spectroscopic structural characterization, along with spectral band assignments calculated by using density functional theory (M06L/cc‐pVDZ and B3LYP/6‐31G(d)), are reported for Fe(OEP)picrate as a model for hemozoin (malaria pigment) and its synthetic analog β‐hematin, which are spectroscopically identical. The average Fe–N distance, 2.044(12) Å, and the Raman modes indicate a high‐spin five‐coordinate iron(III) complex. Resonance enhancement is observed for the totally symmetric oxidation state marker band ν4 along with the characteristic bands of Cβ‐substituted hemes in the ranges of 1621–1639 cm−1 for νas(CαCm) and 750–756 cm−1 for ν(pyr breathing) similar to β‐hematin and hemozoin when using near‐IR excitation wavelengths. The similarity of the resonance Raman spectral profiles for Fe(OEP)picrate and β‐hematin, along with the structural results, indicates that Fe(OEP)picrate is an excellent model for understanding the stereochemistry and intermolecular interaction of β‐hematin. Copyright © 2017 John Wiley & Sons, Ltd.
The value of frontal sinusotomy for chronic rhinosinusitis with nasal polyps—A cost utility analysis
Authors: Scangas George A. , Lehmann Ashton E. , Remenschneider Aaron K. , Su Brooke M. , Shrime Mark G. , Metson Ralph 
Published: August 2017

Objectives/HypothesisThe number of surgical procedures performed for frontal sinusitis and the associated costs have increased dramatically over the past decade. The purpose of this study was to evaluate the cost‐effectiveness of endoscopic frontal sinusotomy (EFS) in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).Study DesignCohort‐style Markov decision‐tree economic model with a 36‐year time horizon.MethodsMatched cohorts of CRSwNP patients who underwent endoscopic sinus surgery (ESS) with (n = 139) and without (n = 49) EFS were compared to each other and to patients (n = 139) from the Medical Expenditures Survey Panel database who underwent medical management for chronic rhinosinusitis. Multi‐year health utility values were calculated from responses to the EuroQol 5‐Dimension instrument. The primary outcome measure was the incremental cost‐effectiveness ratio (ICER).ResultsDecision analysis showed that ESS without EFS proved more cost‐effective than ESS with EFS or medical management. ESS without EFS compared to medical management yielded an ICER of $9,004/quality‐adjusted life year (QALY). ESS with EFS compared to ESS without EFS yielded an ICER of $62,310/QALY. At a willingness‐to‐pay (WTP) threshold of $50,000/QALY, ESS without EFS was more cost‐effective than ESS with EFS with 52.1% certainty. These results were robust to one‐way analysis and probabilistic sensitivity analysis.ConclusionsESS remains a cost‐effective intervention compared to medical therapy alone for patients with CRSwNP. In this study, the addition of frontal sinusotomy during ESS for patients with CRSwNP was not found to be cost‐effective at a WTP threshold of $50,000/QALY, but may be cost effective at a higher threshold of $100,000/QALY.Level of Evidence2c. Laryngoscope, 128:43–51, 2018
Disparities in sinonasal squamous cell carcinoma short‐ and long‐term outcomes: Analysis from the national cancer database
Authors: Carey Ryan M. , Parasher Arjun K. , Workman Alan D. , Yan Carol H. , Glicksman Jordan T. , Chen Jinbo , Palmer James N. , Adappa Nithin D. , Newman Jason G. , Brant Jason A 
Published: August 2017

Objectives/HypothesisTo examine sociodemographic, hospital‐specific, and disease‐related characteristics in relation to outcomes in sinonasal squamous cell carcinoma (SCC).Study DesignThe National Cancer Database was queried for location codes corresponding to the nasal cavity and paranasal sinuses and histology codes representing SCC malignancy. Multivariate analyses were performed against short‐ and long‐term outcomes (overall survival, days to discharge, 30‐day readmission, and 30‐ and 90‐day mortality).ResultsThe database included 5,584 sinonasal SCC patients with an overall median survival of 53.5 months (95% confidence interval [CI]: 49.7‐57.8). On multivariate analysis, uninsured, Medicaid, and Medicare were independently associated with worse overall survival compared to private insurance (hazard ratio [HR]: 1.49, 95% CI: 1.22‐1.82, P < .001; HR: 1.57, 95% CI: 1.34‐1.85, P < .001; and HR: 1.14, 95% CI: 1.01‐1.29, P = .03, respectively). Both Medicaid and Medicare were also associated with increased 30‐day mortality (HR: 1.36, 95% CI: 1.76‐143.29, P = .02; HR: 8.27, 95% CI: 1.66‐70.88, P = .02, respectively), and Medicaid patients spent more time in the hospital following surgery (difference in days to discharge: HR: 2.09, 95% CI: 0.57‐3.61, P < .01). Compared to white race, other race was associated with improved overall survival (HR: 0.79, 95% CI: 0.63‐0.99, P = .04) but increased 30‐day readmissions (HR: 3.85, 95% CI: 1.58‐8.38, P < .01). Hispanic ethnicity was associated with increased 30‐day readmissions (HR: 2.35, 95% CI: 1.08‐4.75, P = .02]. The highest income bracket (≥$63,000) was associated with fewer hospital readmissions (HR: 0.33, 95% CI: 0.13‐0.79, P = .01).ConclusionsSociodemographic and economic differences in outcomes of patients with sinonasal SCC cancer exist. An understanding of these differences may help minimize disparities in oncologic treatment.Level of Evidence2c. Laryngoscope, 128:560–567, 2018
Titanium Dioxide Nanoparticles Improve Growth and Enhance Tolerance of Broad Bean Plants under Saline Soil Conditions
Authors: Abdel Latef Arafat Abdel Hamed , Srivastava Ashish Kumar , El‐sadek Mahmmoud Sayed Abd , Kordrostami Mojtaba , Tran Lam‐Son Phan 
Published: August 2017

AbstractSoil salinity is established as one of the major environmental problems, decreasing crop productivity worldwide, thereby threatening sustainable agriculture. In the present study, we evaluated the effects of titanium dioxide nanoparticles (nTiO2) for ameliorating soil salinity in broad bean, an important leguminous crop. As nTiO2 is known to have pro‐oxidant and antioxidant properties, the effects of three different nTiO2 concentrations (0·01%, 0·02% and 0·03%) were compared with respect to plant growth and stress responses. The 0·01% nTiO2 application significantly increased shoot length, leaf area and root dry weight of plants under normal conditions. These growth‐promoting effects were simultaneous with increased levels of chlorophyll b, soluble sugars and proline and enhanced activities of antioxidant enzymes. Under saline soil conditions, although proline level and enzymatic antioxidant activities were increased, plant growth significantly reduced. The 0·01% nTiO2 supplementation significantly increased the activities of enzymatic antioxidants and levels of soluble sugars, amino acids and proline in salt‐affected plants versus plants subjected to salinity alone. Thus, the increased antioxidant enzyme activities contributed to the observed reduction in hydrogen peroxide and malondialdehyde contents, while enhanced levels of proline and other metabolites contributed to osmoprotection, collectively resulting in significant plant growth improvement under salinity. Furthermore, nTiO2‐mediated positive effects were concentration dependent with 0·01% nTiO2 being the most effective, whereas 0·02% showed an intermediate response and 0·03% was almost ineffective under both control and saline soil conditions. Our findings provide a foundation for nTiO2 application in improving growth of plants cultivated on naturally contaminated saline soils. Copyright © 2017 John Wiley & Sons, Ltd.
Soil Carbon and Nutrient Dynamics Following Cessation of Anthropogenic Disturbances in Degraded Subtropical Forests
Authors: Feng Chun , Ma Yan , Fu Songling , Chen Han Y.H. 
Published: August 2017

AbstractSoil carbon (C) and nutrient availability is fundamental to terrestrial biodiversity and functionality. In recent decades, the restoration of degraded forests has become a major concern worldwide, and recent studies have demonstrated that soil C and nitrogen (N) increase over time following restoration. However, our understanding of the responses of soil phosphorus (P), calcium (Ca), potassium (K) and magnesium (Mg) and elemental stoichiometric ratios to restoration remains elusive. We employed a chronosequence to examine the responses of C and macronutrients in three soil layers (0–10 cm, 10–20 cm and 20–30 cm) to the time (0 to 31 years) since the cessation of anthropogenic disturbances in the degraded subtropical forests of Eastern China. We found that stand basal area, soil water content, organic matter content and C concentration and stock increased, while soil pH and bulk density decreased over time, with the most pronounced effects within the 0–10 cm layer. Total and available N and K as well as available P and total Mg increased, while total P in the 20–30 cm layer and Ca in all soil layers decreased over time. The mass concentration ratios of soil C to total N and available N, P and K decreased, whereas those for C to total P and Ca as well as total N to total P and available N to available P increased over time. Our results suggest that soil C accumulation and biologically driven nutrients increase, while nutrients that are driven primarily through geochemical mechanisms decrease with live biomass accumulation following restoration. Copyright © 2017 John Wiley & Sons, Ltd.