bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors for permanent neurological dysfunction after total aortic arch replacement with regional cerebral oxygen saturation monitoring
Authors: Yu Ying , Lyu Yi , Jin Lin , Xu Liying , Wang Huilin , Hu Yan , Ren Yun , Guo Kefang
Published: May 2019

Objective

To explore the prognostic factors for permanent neurological dysfunction (PND) after total aortic arch replacement with regional cerebral oxygen saturation (rSO2) monitoring.

Methods

This retrospective study enrolled 98 type A aortic dissection aneurysm patients who underwent emergency total aortic arch replacement combined with deep hypothermic circulatory arrest and right axillary artery selective antegrade cerebral perfusion (SACP). Data such as age, gender, body mass index, preoperative coexisting disease, laboratory test results, intraoperative critical operation duration, and intraoperative rSO2 were collected, and the neurological prognoses in the hospital were recorded and grouped by severity. Multiple logistic regression analysis was performed on the statistically significant differences between the groups to screen the predictors of postoperative neurological complications in these patients.

Results

Forty‐two patients had postoperative neurological complications, among which there were 29 cases (29.6%) of transient neurological dysfunction, and 13 cases (13.3%) of PND. Multiple logistic regression results showed that advanced age, preoperative low platelet count, prolonged hemostasis time and lowest relative rSO2 to baseline (ΔrSO2min) in each time period were risk factors for postoperative PND. The ROC curve measurement showed that the optimal cut‐off value of ΔrSO2min was 79.7%, and the area under the curve was 0.708 (95% confidence interval = 0.557–0.858), p = 0.016; the optimal cut‐off value of ΔrSO2min in SACP was 81.6%, and the area under the curve was 0.720 (95% confidence interval = 0.570–0.870), p = 0.011; the optimal cut‐off value of ΔrSO2min in cardiopulmonary bypass (CPB) was 80.8%, and the area under the curve was 0.697 (95% confidence interval = 0.554–0.840), p = 0.023.

Conclusion

Intraoperative ΔrSO2min that is lower than the basal level of about 80%, advanced age, preoperative low platelet count, and prolonged hemostasis time are predictors of PND after total aortic arch replacement.
Promyelocytic leukemia protein deficiency leads to spontaneous formation of liver tumors in hepatitis C virus transgenic mice
Authors: Straub Katja , Husen Peri , Baba Hideo A. , Trippler Martin , Wedemeyer Heiner , Herzer Kerstin
Published: May 2019

Persistent infection with hepatitis C virus (HCV) is a known risk factor for the development of hepatocellular carcinoma (HCC). The lack of the tumor suppressor promyelocytic leukemia protein (PML) in combination with HCV fosters hepatocarcinogenesis via induction of HCC using diethylnitrosamine (DEN) in a rodent model. However, the spontaneous development of malignant lesions in PML‐deficient mice with an HCV‐transgene (HCVtg) has not been investigated thus far. We crossed PML‐deficient mice with HCV transgene expressing mice and observed the animals for a period of 12 months. Livers were examined macroscopically and histologically. Gene expression analysis was performed on these samples, and compared with expression of selected genes in human samples of patients undergoing liver transplantation for HCC. In vitro studies were performed in order to analyze the selected pathways. Genetic depletion of PML in combination with HCVtg coincided with an increased hepatocyte proliferation, resulting in development of HCCs in 40% of the PML‐deficient livers. No tumor development was observed in mice with either the PML‐knockout (PML−/−) or HCVtg alone. Gene expression profiling uncovered pathways involved in cell proliferation, such as NLRP12 and RASFF6. These findings were verified in samples from human livers of patients undergoing liver transplantation for HCC. Further in vitro studies confirmed that lack of PML, NLRP12, and RASFF6 leads to increased cell proliferation. The lack of PML in combination with HCV is associated with increased cell proliferation, fostering tumor development in the liver. Our data demonstrate that PML acts as an important tumor suppressor in HCV‐dependent liver pathology.
Bonding social capital and collective action: Associations with residents' perceptions of their neighbourhoods
Authors: Carbone Jason T.
Published: May 2019

Neighbourhood perceptions have important implications for individual well‐being, yet there is limited research focused on variables that predict these perceptions. This study proposes that previous engagement in collective action mediates the relationship between neighbourhood bonding social capital and neighbourhood perceptions. Structural equation modelling with a large, nationally representative sample (N = 25,370) is used to test the hypotheses. The findings suggest that bonding social capital has a positive, direct effect on both neighbourhood perceptions and collective action. Collective action has a negative, direct association with neighbourhood perceptions and bonding social capital has a negative, indirect effect on neighbourhood perceptions via collective action. Although the full model explains 28% of the variance in neighbourhood perceptions, bonding social capital only explains 5% of the variance in collective action.
The Application of Isoacyl Structural Motifs in Prodrug Design and Peptide Chemistry
Authors: Mailig Melrose , Liu Fa
Published: May 2019

Intramolecular N‐to‐O and O‐to‐N acyl migrations have been known for a century. Recent decades have witnessed a considerable number of applications of such chemical transformations in the fields of medicinal chemistry and peptide chemistry. The former has been focused on employing the isoacyl‐mediated prodrug approach to improve the physicochemical properties of insoluble drug candidates. The latter involves multiple directions, including establishing new peptide segment ligation methods; facilitating sterically hindered amide‐bond coupling; and enabling the synthesis, handling and investigation of difficult sequences. Notably, most of these cases can be achieved in a traceless manner. These successes are mainly attributed to the unique chemical and biophysical properties of the isoacyl structural motif. This review will summarize the historical achievements and highlight the recent advances in this topic.
Carbon Nanofibers Provide a Cationic Rectifier Material: Specific Electrolyte Effects, Bipolar Reactivity, and Prospect for Desalination
Authors: Tshwenya Luthando , Marken Frank , Arotiba Omotayo A.
Published: May 2019

We demonstrate that ionic current rectification effects are observed with a film of negatively charged carbon nanofibers (CNFs) deposited as a film or mat onto a 10 μm diameter microhole in poly‐ethylene‐terephthalate (PET). CNFs are synthesized by using a chemical vapor deposition (CVD) method, followed by oxidation with hydrogen peroxide to introduce carboxyl moieties (providing negative surface charges). CNFs are characterized with transmission electron microscopy, scanning electron microscopy, elemental analysis, and zeta potential measurements. When drop‐dried asymmetrically onto a 10 μm diameter cylindrical channel on a 6 μm thick PET substrate and placed as a membrane between two electrolyte compartments, ionic current rectification is observed. Effects of pH, ionic strength, and nature of electrolyte are investigated. Bipolar reactivity of iodide is demonstrated. Potential for future applications in water purification are discussed.
The First Conducting Spin‐Crossover Compound Combining a MnIII Cation Complex with Electroactive TCNQ Demonstrating an Abrupt Spin Transition with a Hysteresis of 50 K
Authors: Kazakova Anna V. , Tiunova Aleksandra V. , Korchagin Denis V. , Shilov Gennady V. , Yagubskii Eduard B. , Zverev Vladimir N. , Yang Shun Cheng , Lin Jiunn‐Yuan , Lee Jyh‐Fu , Maximova Olga V. , Vasiliev Alexander N.
Published: May 2019

We present herein the synthesis, crystal structure, and electric and magnetic properties of the spin‐crossover salt [Mn(5‐Cl‐sal‐N‐1,5,8,12)]TCNQ1.5⋅2 CH3CN (I), where 5‐Cl‐sal‐N‐1,5,8,12=N,N′‐bis(3‐(2‐oxy‐5‐chlorobenzylideneamino)propyl)‐ethylenediamine, containing distinct conductive and magnetic blocks along with acetonitrile solvent molecules. The MnIII complex with a Schiff‐base ligand, [Mn(5‐Cl‐sal‐N‐1,5,8,12)]+, acts as the magnetic unit, and the π‐electron acceptor 7,7,8,8‐tetracyanoquinodimethane (TCNQ−) is the conducting unit. The title compound (I) exhibits semiconducting behavior with room temperature conductivity σRT≈1×10−4 ohm−1 cm−1 and activation energy Δ ≈0.20 eV. In the temperature range 73–123 K, it experiences a hysteretic phase transition accompanied by a crossover between the low‐spin S=1 and high‐spin S=2 states of MnIII and changes in bond lengths within the MnN4O2 octahedra. The pronounced shrinkage of the basal Mn−N bonds in I at the spin crossover suggests that the d
orbital is occupied/deoccupied in this transition. Interestingly, the bromo isomorphic counterpart [Mn(5‐Br‐sal‐N‐1,5,8,12)]TCNQ1.5⋅2 CH3CN (II) of the title compound evidences no spin‐crossover phenomena and remains in the high‐spin state in the temperature range 2–300 K. Comparison of the chloro and bromo compounds allows the thermal and spin‐crossover contributions to the overall variation in bond lengths to be distinguished. The difference in magnetic behavior of these two salts has been ascribed to intermolecular supramolecular effects on the spin transition. Discrete hydrogen bonding exists between cations and cations and anions in both compounds. However, the hydrogen bonding in the crystals of II is much stronger than in I. The relatively close packing arrangement of the [Mn(5‐Br‐sal‐N‐1,5,8,12)]+ cations probably precludes their spin transformation.
System Structure and Network Computing Architecture of Petrochemical Cyber‐Physical System: Overview and Perspective
Authors: Li Defang , Suo Hansheng , Liu Wei
Published: May 2019

The cyber‐physical system (CPS) has become the key infrastructure to support the development of smart manufacturing. On the basis of analyzing the CPS theory and industrial characteristics of the petrochemical industry, this paper defines the system structure of the CPS in petrochemical called petrochemical cyber‐physical system (PCPS), and divides PCPS into three system structure levels, proceeding from the analysis on the overall development of the petrochemical industry and the production situation of Sinopec Group. On the basis of this system structure, the unit pattern structure, unit level structure, network architecture, computing architecture, and working model of PCPS are studied and analyzed. Finally, this paper introduces the application scenario of PCPS in the construction of a Sinopec smart factory.
A very personal war
Authors: Khuri Fadlo R.
Published: May 2019

Despite several important new accomplishments, including making campuses tobacco free, the fields of medicine and public health and their communities must stay vigilant to the harms of tobacco, especially with regard to new products and new approaches led by tobacco companies. The war on Big Tobacco and the harms it causes must continue as the focus of these companies shifts away from adult smokers in Western countries toward youth and the developing world.
Porphyrin‐based bridged silsesquioxane nanoparticles for targeted two‐photon photodynamic therapy of zebrafish xenografted with human tumor
Authors: Dib Soraya , Aggad Dina , Mauriello Jimenez Chiara , Lakrafi Ahmed , Hery Guillaume , Nguyen Christophe , Durand Denis , Morère Alain , El Cheikh Khaled , Sol Vincent , Chaleix Vincent , Dominguez Gil Sofia , Bouchmella Karim , Raehm Laurence , Durand Jean‐Olivier , Boufatit Makhlouf , Cattoën Xavier , Wong Chi Man Michel , Bettache Nadir , Gary‐Bobo Magali
Published: May 2019

Background

Bridged silsesquioxane nanoparticles (BSNs) recently described represent a new class of nanoparticles exhibiting versatile applications and particularly a strong potential for nanomedicine.

Aims

In this work, we describe the synthesis of BSNs from an octasilylated functional porphyrin precursor (PORBSNs) efficiently obtained through a click reaction. These innovative and very small‐sized nanoparticles were functionalized with PEG and mannose (PORBSNs‐mannose) in order to target breast tumors in vivo.

Methods and Results

The structure of these nanoparticles is constituted of porphyrins J aggregates that allow two‐photon spatiotemporal excitation of the nanoparticles. The therapeutic potential of such photoactivable nanoparticles was first studied in vitro, in human breast cancer cells in culture and then in vivo on zebrafish embryos bearing human tumors. These animal models were intravenously injected with 5 nL of a solution containing PORBSNs‐mannose. An hour and half after the injection of photoactivable and targeted nanoparticles, the tumor areas were excited for few seconds with a two‐photon beam induced focused laser. We observed strong tumor size decrease, with the involvement of apoptosis pathway activation.

Conclusion

We demonstrated the high targeting, imaging, and therapeutic potential of PORBSNs‐mannose injected in the blood stream of zebrafish xenografted with human tumors.
Comparison between Hydrogen and Halogen Bonds in Complexes of 6‐OX‐Fulvene with Pnicogen and Chalcogen Electron Donors
Authors: Hou Mingchang , Li Qingzhong , Scheiner Steve
Published: May 2019

Quantum chemical calculations are applied to complexes of 6‐OX‐fulvene (X=H, Cl, Br, I) with ZH3/H2Y (Z=N, P, As, Sb; Y=O, S, Se, Te) to study the competition between the hydrogen bond and the halogen bond. The H‐bond weakens as the base atom grows in size and the associated negative electrostatic potential on the Lewis base atom diminishes. The pattern for the halogen bonds is more complicated. In most cases, the halogen bond is stronger for the heavier halogen atom, and pnicogen electron donors are more strongly bound than chalcogen. Halogen bonds to chalcogen atoms strengthen in the order O<S<Se<Te, whereas the pattern is murkier for the pnicogen donors. In terms of competition, most halogen bonds to pnicogen donors are stronger than their H‐bond analogues, but there is no clear pattern with respect to chalcogen donors. O prefers a H‐bond, while halogen bonds are favored by Te. For S and Se, I‐bonds are strongest, followed Br, H, and Cl‐bonds in that order.
Diphenylene‐Tetracyanoquinodimethane Cocrystals as Stable Organic Rectifiers
Authors: Li Rui , Li Jinfeng , Sun Yajing , Zhang Xiaotao , Hu Wenping
Published: May 2019

A promising cocrystal material that acts as a rectifier was prepared by a simple procedure of solution volatilization. (E)‐1,2‐diphenylethene (STB) and 7,7′,8,8′‐tetracyanoquinodimethane (TCNQ) were used as donor and acceptor respectively, and aggregate in an ordered fashion in the stilbene‐tetracyanoquinodimethane (STC) cocrystal that comprises 1 : 1 donor/acceptor mixed‐stacked charge‐transfer (CT) complexes. The strong CT interaction between the donor and acceptor is the main driving force for the self‐assembly. The cocrystals show rectifying characteristics with a rectification ratio of 26. This result suggests that cocrystal engineering provides a great possibility to obtain rectifying materials from small, readily available organic molecules.
A Samarium‐Doped Carbon Aerogel Cathode with Anchored Polysulfides for Lithium−Sulfur Batteries with High Electrochemical Performance: A Metal−Organic Framework Template Method
Authors: Sheng Huijuan , Li Xueliang , Huang Birou , Wang Jihong , Li Xiaoyang , Hua Yang
Published: May 2019

A samarium‐doped carbon aerogel cathode (CA‐Sm) for high‐performance lithium−sulfur batteries was successfully synthesized from a Sm‐containing metal−organic framework (MOF) as a template through a sol−gel reaction and a carbonization process. Sm‐MOF doping plays an important role in regulating the structure of the gel and promoting the formation of samarium oxide in an amorphous state that is uniformly dispersed among the carbon spheres. A CA/S/Sm electrode delivers an initial discharge capacity of 1322 mAh g−1 at a rate of 0.2 C. Furthermore, it possesses an initial discharge capacity of 1212 mAh g−1at 0.5 C and still maintains a value of 866 mAh g−1 after 300 cycles. Both the anchoring of polysulfides to uniformly doped Sm and the influence of the Sm‐MOF on the CA structure lead to the excellent performance of the battery, and effectively prevent polysulfides escaping from cathode, while suppressing the shuttle effect and enhancing the utilization of sulfur.
An Indacenodithieno[3,2‐b]thiophene‐Based Organic Dye for Solid‐State p‐Type Dye‐Sensitized Solar Cells
Authors: Xu Bo , Wrede Sina , Curtze Allison , Tian Lei , Pati Palas Baran , Kloo Lars , Wu Yiying , Tian Haining
Published: May 2019

An indacenodithieno[3,2‐b]thiophene (IDTT) unit is used as a linker moiety to design a new p‐type dye—TIP—for solid‐state p‐type dye‐sensitized solar cells. Solar cells based on the TIP dye offered an efficiency of 0.18 % with an open‐circuit photovoltage of 550 mV and a short‐circuit photocurrent density of 0.86 mA cm−2, which is better than those of two reference dyes, PB6 and BH4. Charge lifetime experiments reveal that the IDTT linker‐based TIP dye significantly suppresses charge recombination losses in the devices.
Tale of two Indians: Heterogeneity in type 2 diabetes pathophysiology
Authors: Staimez Lisa R. , Deepa Mohan , Ali Mohammed K. , Mohan Viswanathan , Hanson Robert L. , Narayan K.M. Venkat
Published: May 2019

Aims

Type 2 diabetes is a heterogeneous disease and may manifest from multiple disease pathways. We examined insulin secretion and insulin resistance across two ethnicities with particularly high risk for diabetes yet with widely different distributions of weight class.

Materials and Methods

In this population‐based, cross‐sectional study, Pima Indians from Southwestern United States (n = 865) and Asian Indians from Chennai, India (n = 2374) had a 75‐g oral glucose tolerance test. We analysed differences in plasma glucose, plasma insulin, insulin resistance (HOMA‐IR), and insulin secretion (ΔI0‐30/ΔG0‐30) across categories of body mass index (BMI) and glycemic status per American Diabetes Association criteria.

Results

Pima Indians were younger (mean 27.4 ± SD 6.6, Asian: 33.9 ± 6.7 years) and had higher BMI (33.6 ± 8.1, Asian: 25.7 ± 4.9 kg/m2). Among normal weight participants (mean BMI: Pima 22.4 SE 0.2; Asian 22.2 SE 0.06 kg/m2), fasting glucose was higher in Asian Indians (5.2 vs Pima: 4.8 mmol/L, P = .003), adjusted for age and sex. Pima Indians were three times as insulin resistant as Asian Indians (HOMA‐IR: 7.7 SE 0.1, Asian: 2.5 SE 0.07), while Asian Indians had three times less insulin secretion (Pima: 2.8 SE 1.0 vs Asian: 0.9 SE 1.0 pmol/mmol), a pattern evident across age, BMI, and glycemic strata.

Conclusions

Metabolic differences between Pima and Asian Indians suggest heterogeneous pathways of type 2 diabetes in the early natural history of disease, with emphasis of insulin resistance in Pima Indians and emphasis of poor insulin secretion in Asian Indians.
Parthenogenetic vs. sexual reproduction in oribatid mite communities
Authors: Maraun Mark , Caruso Tancredi , Hense Jonathan , Lehmitz Ricarda , Mumladze Levan , Murvanidze Maka , Nae Ioana , Schulz Julia , Seniczak Anna , Scheu Stefan
Published: May 2019

The dominance of sex in Metazoa is enigmatic. Sexual species allocate resources to the production of males, while potentially facing negative effects such as the loss of well‐adapted genotypes due to recombination, and exposure to diseases and predators during mating. Two major hypotheses have been put forward to explain the advantages of parthenogenetic versus sexual reproduction in animals, that is, the Red Queen hypothesis and the Tangled Bank/Structured Resource Theory of Sex. The Red Queen hypothesis assumes that antagonistic predator—prey/ parasite–host interactions favor sex. The Structured Resource Theory of Sex predicts sexual reproduction to be favored if resources are in short supply and aggregated in space. In soil, a remarkable number of invertebrates reproduce by parthenogenesis, and this pattern is most pronounced in oribatid mites (Oribatida, Acari). Oribatid mites are abundant in virtually any soil across very different habitats, and include many sexual and parthenogenetic (thelytokous) species. Thereby, they represent an ideal model group to investigate the role of sexual versus parthenogenetic reproduction across different ecosystems and habitats. Here, we compiled data on oribatid mite communities from different ecosystems and habitats across biomes, including tropical rainforests, temperate forests, grasslands, arable fields, salt marshes, bogs, caves, and deadwood. Based on the compiled dataset, we analyzed if the percentage of parthenogenetic species and the percentage of individuals of parthenogenetic species are related to total oribatid mite density, species number, and other potential driving factors of the reproductive mode including altitude and latitude. We then interpret the results in support of either the Red Queen hypothesis or the Structured Resource Theory of Sex. Overall, the data showed that high density of oribatid mites, indicating abundance of resources, is associated with high frequency of parthenogenesis supporting predictions of the Structured Resource Theory of Sex rather than the Red Queen hypothesis.
Th2 cell‐derived IL‐4/IL‐13 promote ILC2 accumulation in the lung by ILC2‐intrinsic STAT6 signaling in mice
Authors: Symowski Cornelia , Voehringer David
Published: May 2019

Infection of mice with the gastrointestinal helminth Nippostrongylus brasiliensis elicits profound local proliferation and accumulation of type 2 innate lymphoid cells (ILC2s) in the lung. The regulation of ILC2 proliferation and accumulation in the lung is poorly understood. Using T cell‐specific IL‐4/IL‐13‐deficient mice, we demonstrate that IL‐4/IL‐13 secretion from Th2 cells promotes proliferation and expansion of the ILC2 population in the lung of N. brasiliensis‐infected mice. Competitive mixed BM chimeras containing normal and STAT6‐deficient ILC2s further indicated that ILC2s have to respond directly to IL‐4/IL‐13 for this effect while STAT6 is not required for IL‐13 production in ILC2s. In addition, expression of a constitutively active form of STAT6 in ILC2s was sufficient to promote their proliferation in uninfected mice. The expression of MHC class II in ILC2s appeared to be enhanced by STAT6 signaling supporting the concept that Th2 cells and ILC2s can communicate in an antigen‐dependent manner resulting in a Th2‐regulated accumulation of ILC2s in the lung during an acute type 2 immune response. Based on our observations, targeting the STAT6 pathway in ILC2s could help to develop new treatments to dampen ILC2 proliferation in the lung and thereby ameliorate ILC2‐mediated allergic inflammation.
Synthesis and Properties of New Multiple TCNE Adducts from Dialkynyl‐N‐(het)arylpyrroles
Authors: Pierrat Philippe , Cebrián Cristina , Beley Marc , Gros Philippe C. , Torres‐Moya Iván , Prieto Pilar , Hesse Stéphanie
Published: May 2019

We report the synthetic routes to mono‐ and di‐TCBD adducts onto N‐(het)arylpyrrole derivatives. We present herein two series of panchromatic chromophores bearing different combinations of donor–acceptor moieties. Additionally, we observe an impact of the nature of the central core. Cyclic voltammograms show very different behaviors at negative potentials between the two series. Particularly, four waves are observed for symmetrical di‐TCDB adducts, thus indicating a communication through the central unit despite the non‐planarity of these molecules.
Awe and meaning: Elucidating complex effects of awe experiences on meaning in life
Authors: Rivera Grace N. , Vess Matthew , Hicks Joshua A. , Routledge Clay
Published: May 2019

Research on the experience of awe suggests that awe has positive impacts on outcomes like life satisfaction and belongingness. No published work, however, has reported effects of awe on the experience of meaning in life. We reasoned that awe might have complicated effects on meaning. On the one hand, many awe experiences likely contain a positive flavor that contributes to both awe and general positive affectivity (happiness). Positive affectivity has a robust positive effect on meaning in life, suggesting that positive awe experiences might increase meaning. At the same time, however, awe experiences lead to a diminished self that reflects feelings of smallness and insignificance, which might negatively predict meaning. We thus hypothesized that awe experiences can, in some contexts, produce competing indirect effects on judgments of meaning in life through happiness and small‐self feelings. The results of five studies (N = 1,690) supported these predictions.
Breeding runner bean for short‐day adaptation, grain yield, and disease resistance in eastern Africa
Authors: Kimani Paul M. , Njau Serah , Mulanya Mabel , Narla Rama D.
Published: May 2019

Runner bean (Phaseolus coccineus L.), also known as butter bean in Kenya, is a high value vegetable and grain crop traditionally grown in high altitudes (>1,800 m) of eastern Africa for domestic consumption and processing. However, it has not received attention from breeders. Consequently, farmers rely on low‐yielding landraces which are susceptible to diseases. Available long‐day vegetable type varieties are poorly adapted to tropical conditions. In 2005, a regional program was initiated at the University of Nairobi to develop tropically adapted short‐day varieties with better agronomic potential to meet both producer and consumer requirements. The objective of this study was to determine the agronomic potential of advanced grain‐type runner bean lines selected from populations derived from crosses between local landraces and long‐day European varieties. Fifty lines were selected from 139 F6.8 lines based on their previous performance at Kabete Field Station and Ol Joro Orok in 2012 and 2013. The 50 lines were evaluated at both sites during the 2014 long rain season. The best 20 lines from both sites were further evaluated for agronomic characteristics, disease resistance, and yield. Results showed considerable variation for duration to flowering (40–55 days at three different sites), plant vigor, racemes per plant, reaction to diseases, and grain yield. The crop was extremely vigorous in Naivasha due to supplementary irrigation and fertilization regimes. The results indicated that new high‐yielding grain runner bean varieties with resistance to major diseases and tropical adaptation can contribute to improved productivity, food and nutritional security, and resilient livelihoods in the region, and regular supply of raw materials for the canning industry.
Ensemble modelling of ice cover for a reservoir affected by pumped‐storage operation and climate change
Authors: Kobler Ulrike Gabriele , Schmid Martin
Published: May 2019

Ensemble modelling was used to assess the robustness of projected impacts of pumped‐storage (PS) operation and climate change on reservoir ice cover. To this end, three one‐dimensional and a two‐dimensional laterally averaged hydrodynamic model were set up. For the latter, the strength of the impacts with increasing distance from the dam was also investigated. Climate change effects were simulated by forcing the models with 150 years of synthetic meteorological time series created with a weather generator based on available air temperature scenarios for Switzerland. Future climate by the end of the 21st century was projected to shorten the ice‐covered period by ~2 months and decrease ice thicknesses by ~13 cm. Under current climate conditions, the ice cover would already be affected by extended PS operation. For example, the average probability of ice coverage on a specific day was projected to decrease by ~13% for current climate and could further be reduced from ~45% to ~10% for future climate. Overall, the results of all models were consistent. Although the number of winters without ice cover was projected to increase for all one‐dimensional models, studying individual segments of the two‐dimensional model showed that the impact was pronounced for segments close to the PS intake/outlet. In summary, the reservoir's ice cover is expected to partially vanish with higher probability of open water conditions closer to the PS intake/outlet.
A novel lncRNA‐LINC01116 regulates tumorigenesis of glioma by targeting VEGFA
Authors: Ye Jingliang , Zhu Junle , Chen Huairui , Qian Jun , Zhang Lei , Wan Zhiping , Chen Feng , Sun Shuhan , Li Wen , Luo Chun
Published: May 2019

Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA‐LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA‐LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR‐31‐5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR‐31‐5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR‐31‐5p‐RISC complex, and biotinylated miR‐31‐5p pull‐down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR‐31‐5p. Collectively, our study has identified a novel lncRNA‐LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma.
MicroRNA‐25 aggravates Aβ1‐42‐induced hippocampal neuron injury in Alzheimer's disease by downregulating KLF2 via the Nrf2 signaling pathway in a mouse model
Authors: Duan Qiang , Si Erwang
Published: May 2019

Recently, numerous microRNAs (miRNAs) have been considered as key players in the regulation of neuronal processes. The purpose of the present study is to explore the effect of miR‐25 on hippocampal neuron injury in Alzheimer's disease (AD) induced by amyloid β (Aβ) peptide fragment 1 to 42 (Aβ1‐42) via Kruppel‐like factor 2 (KLF2) through the nuclear factor‐E2‐related factor 2 (Nrf2) signaling pathway. A mouse model of AD was established through Aβ1‐42 induction. The underlying regulatory mechanisms of miR‐25 were analyzed through treatment of miR‐25 mimics, miR‐25 inhibitors, or small interfering RNA (siRNA) against KLF2 in hippocampal tissues and cells isolated from AD mice. The targeting relationship between miR‐25 and KLF2 was predicted using a target prediction program and verified by luciferase activity determination. MTT assay was used to evaluate the proliferative ability and flow cytometry to detect cell cycle distribution and apoptosis. KLF2 was confirmed as a target gene of miR‐25. When the mice were induced by Aβ1‐42, proliferation was suppressed while apoptosis was promoted in hippocampal neurons as evidenced by lower levels of KLF2, Nrf2, haem oxygenase, glutathione S transferase α1, glutathione, thioredoxin, and B‐cell lymphoma‐2 along with higher bax level. However, such alternations could be reversed by treatment of miR‐25 inhibitors. These findings indicate that miR‐25 may inhibit hippocampal neuron proliferation while promoting apoptosis, thereby aggravating hippocampal neuron injury through downregulation of KLF2 via the Nrf2 signaling pathway.
MicroRNA‐421 inhibition alleviates bronchopulmonary dysplasia in a mouse model via targeting Fgf10
Authors: Yuan Hua‐Shu , Xiong Dai‐Qun , Huang Fang , Cui Jian , Luo Hui
Published: May 2019

Bronchopulmonary dysplasia (BPD) is a common and refractory disease affecting newborn children and infants with alveolar dysplasia and declined pulmonary function. Several microRNAs (miRNAs) have been found to be differentially expressed in BPD progression. This study further explores the role of miR‐421 via fibroblast growth factor 10 (Fgf10) in mice with BPD. A mouse model of BPD was established through the induction of hyperoxia, in which the expression pattern of miR‐421 and Fgf10 was identified. Furthermore, adenovirus‐packed vectors were injected in mice to intervene miR‐421 and Fgf10 expression, including miR‐421 mimics or inhibitors, and si‐Fgf10 to explore the role of miR‐421 and Fgf10 in BPD. The target relationship between miR‐421 and Fgf10 was investigated. Inflammatory response and cell apoptosis were observed in the mice, with inflammatory cytokines and apoptosis‐related factors detected by applying Reverse transcription quantitative polymerase chain reaction, Western blot analysis, and enzyme‐linked immunosorbent assay. Fgf10 was confirmed as a target gene of miR‐421. Elevated expression of miR‐421 was evident, while Fgf10 was poorly expressed in BPD. upregulation of miR‐421 and silence of Fgf10 aggravated inflammatory response in lung tissue and promoted lung cell apoptosis in BPD. The aforementioned alterations could be reversed by downregulation of miR‐421. Collectively, inhibition of miR‐421 can assist in the development of BPD in mice BPD by upregulating Fgf10. Therefore, the present study provides a probable target for the treatment of BPD.
Retracted: Silence of lncRNA HEIH suppressed liver cancer cell growth and metastasis through miR‐199a‐3p/mTOR axis
Authors: Ma Yongbiao , Cao De , Li Gaoxue , Hu Jingxia , Liu Xin , Liu Jianling
Published: May 2019

Background/Aims

High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines.

Methods

The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied.

Results

As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl‐2, MMP‐2, MMP‐8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase‐3. MicroRNA (miR)‐199a‐3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR‐199a‐3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR‐199a‐3p.

Conclusion

HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR‐199a‐3p, and thereby blockage of mTOR signaling.
PTEN improve renal fibrosis in vitro and in vivo through inhibiting FAK/AKT signaling pathway
Authors: Du Yongchao , Liu Peihua , Chen Zhi , He Yao , Zhang Bo , Dai Guoyu , Xia Weiping , Liu Yuhang , Chen Xiang
Published: May 2019

Renal ﬁbrosis, the ultimate common pathway of progressive nephropathy, is characterized by excess accumulation and deposition of extracellular matrix (ECM) within the renal interstitium and glomeruli, finally resulting in end‐stage kidney failure. TGFβ1 is not only abnormally increased during fibrosis but also involved in ECM induction and accumulation. Based on the bioinformative analyses, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and focal adhesion kinase (FAK) signaling pathway might be involved in TGFβ1 functions on renal fibrosis development. In the present study, fibrosis was induced in HK‐2 cells using TGFβ1 and PTEN expression was significantly suppressed by 24 or 48 hours TGFβ1 treatment. PTEN overexpression in HK‐2 cells improved TGFβ1‐induced fibrosis within α‐SMA and E‐cadherin. According to the KEGG signaling pathway annotation analyses on microarray profiles (GSE23338 and GSE20247) and immunoblotting validation, FAK signaling might be involved in PTEN functions in TGFβ1‐induced fibrosis. PTEN overexpression significantly inhibited TGFβ1‐ or unilateral ureteral obstruction (UUO)‐induced FAK signaling pathway activation both in vitro and in vivo; more importantly, PTEN silence enhanced TGFβ1‐ or UUO‐induced fibrosis, while FAK inhibitor PF567721 significantly reversed the effects of PTEN silence, indicating that PTEN exerted its effects on TGFβ1‐ and UUO‐induced fibrotic development in vitro and in vivo via inhibiting FAK signaling pathway. In summary, these findings indicate that PTEN could improve cellular fibrotic changes and renal fibrosis via inhibiting FAK/AKT signaling pathway. Restoring PTEN expression to target FAK/AKT signaling pathway might be a potent strategy for renal fibrosis treatment.
Association analysis of the common varieties of IL17A and IL17F genes with the risk of knee osteoarthritis
Authors: Bafrani Hassan Hassani , Ahmadi Monavvareh , Jahantigh Danial , Karimian Mohammad
Published: May 2019

Osteoarthritis is mediated by various types of cytokines, growth factors, and inflammatory factors that the role of the interleukin‐17 family in this disease is becoming increasingly apparent. The aim of this study is to determine the association between the common polymorphisms of IL17A (including rs2275913) and IL17F (including rs2397084 and rs763780) genes with the knee osteoarthritis risk which was followed by a bioinformatics approach. In a case‐control study, 254 participants consisting of 127 healthy individuals and 127 subjects with knee osteoarthritis referring to Shahid Beheshti Hospital dependents on Kashan University of Medical Sciences (Kashan, Iran) were enrolled. After samples collection, the polymorphisms genotyping was determined by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. Finally, some bioinformatics tools were used to analyze the molecular effects of the three studied polymorphisms. Data analysis showed a significant association between rs2275913‐GA genotype and the decreased risk of knee osteoarthritis (OR = 0.57, 95% CI = 0.33‐0.97, P = .040). However, rs763780‐AG genotype (OR = 2.29, 95%CI = 1.11‐4.69, P = .024) and rs763780‐G allele (OR = 2.01, 95% CI = 1.09‐3.72, P = .026) were associated with an increased risk of knee osteoarthritis. However, no significant associations were found between the rs2397084 polymorphism and knee osteoarthritis risk. Our structural analysis revealed that the rs2275913 polymorphism could create a new binding site for TFII‐I at the promoter region of IL17A. Also, rs2397084 and rs763780 could significantly affect the function and structure of IL17A. Based on our findings, rs2275913 and rs763780 could be considered as protective and risk factors for knee osteoarthritis, respectively. Therefore, these polymorphisms can be considered as biomarkers for the screening of knee osteoarthritis susceptible persons.
Wnt7a, frequently silenced by CpG methylation, inhibits tumor growth and metastasis via suppressing epithelial‐mesenchymal transition in gastric cancer
Authors: Liu Yuzhen , Qiao Yanchun , Zhang Hangyu , Li Wentong , Zheng Jie
Published: May 2019

Wnt7a is a member of the Wnt family and has been reported to be involved in the carcinogenesis and progression of many types of human cancer. However, little is known about Wnt7a expression and function in gastric cancer (GC). In the present study, Wnt7a expression in GC tissues and cells was investigated, the correlation between Wnt7a expression and the prognosis was also examined. The effects of Wnt7a on proliferation, invasion, and metastasis were evaluated in vitro and in vivo. Furthermore, the expression of epithelial‐mesenchymal transition (EMT) markers and hypermethylation of the Wnt7a promoter were both detected. Wnt7a was downregulated in GC and its expression was associated with poor prognosis of patients with GC. Moreover, upregulation of Wnt7a significantly suppressed the growth, invasion, and metastasis abilities of GC cells in vitro and in vivo. Mechanistically, Wnt7a was found to inhibit EMT process of GC cells. In addition, the reducing expression of Wnt7a was due to methylation of 5′‐CpG island within the promoter. Furthermore, the tumor suppressor role of Wnt7a is independent of canonical Wnt/β‐catenin signaling in GC cells. In conclusion, our findings demonstrated that Wnt7a could be used as a potential diagnostic marker and target for GC management.
LncRNA MEG3 contributes to adenosine‐induced cytotoxicity in hepatoma HepG2 cells by downregulated ILF3 and autophagy inhibition via regulation PI3K‐AKT‐mTOR and beclin‐1 signaling pathway
Authors: Pu Zejin , Wu Lingfei , Guo Yitian , Li Guoping , Xiang Mengqi , Liu Lixuan , Zhan Haolian , Zhou Xiaotao , Tan Hui
Published: May 2019

Adenosine is a promising cytotoxic reagent for tumors, long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been indicated to play critical roles in tumorigenesis, ILF3 has been recognized as a MEG3‐binding protein, however, the roles of adenosine and MEG3 on hepatoma are still ambiguous. To clarify the effects of MEG3 on the adenosine‐induced cytotoxicity in hepatoma, MEG3 and ILF3 lentivirus were transduced into human hepatoma HepG2 cells to stimulate overexpression of MEG3 (OE MEG3) and overexpression of ILF3 (OE ILF3), furthermore, ILF3 small interfering RNA (siRNA) was also applied to downregulate the expression of ILF3. In this study, autophagy was markedly inhibited by low concentration of adenosine, which present by not only inhibited transformation from LC3‐I to LC3‐II and autophagosomes formation, but also the elevation of mTOR and reduction of beclin‐1 proteins. Furthermore, low concentration of adenosine also exerted marked cytotoxicity representing induced cell apoptosis together with reductions of cell viability and migration, which were also markedly enhanced by OE MEG3. Novelly and excitingly, adenosine markedly stimulated MEG3 expression, OE MEG3 markedly decreased the ILF3 expression in HepG2 cells, and the adenosine‐induced autophagy inhibition, together with the ratio of p‐PI3K/PI3K, p‐AKT/AKT, and p‐mTOR/mTOR were also boosted by OE MEG3. More interestingly, OE ILF3 increased autophagy, whereas downregulated ILF3, especially in the case of adenosine, led to marked autophagy inhibition by decreasing beclin‐1. The present study demonstrates autophagy inhibition is involved in the adenosine‐induced cytotoxicity in HepG2 cells, the cytotoxicity can be synergized by OE MEG3 via downregulated ILF3 to activate PI3K/Akt/mTOR and inactivate the beclin‐1 signaling pathway. In conclusion, MEG3 and inhibition of autophagy might be potential targets for augmenting adenosine‐induced cytotoxicity in hepatoma.
TGF‐β1 downregulation in the hypothalamus of obese mice through acute exercise
Authors: Silva Vagner R. R. , Lenhare Luciene , Katashima Carlos K. , Morari Joseane , M‐Assis Alexandre , Gaspar Rodrigo S. , da Silva Adelino S. R. , Moura Leandro P. , Pauli José R. , Cintra Dennys E. , Velloso Licio A. , Ropelle Eduardo R.
Published: May 2019

Obesity and aging lead to abnormal transforming growth factor‐β1 (TGF‐β1) signaling in the hypothalamus, triggering the imbalance on glucose metabolism and energy homeostasis. Here, we determine the effect of acute exercise on TGF‐β1 expression in the hypothalamus of two models of obesity in mice. The bioinformatics analysis was performed to evaluate the correlation between hypothalamic Tgf‐β1 messenger RNA (mRNA) and genes related to thermogenesis in the brown adipose tissue (BAT) by using a large panel of isogenic BXD mice. Thereafter, leptin‐deficient (ob/ob) mice and obese C57BL/6 mice fed on a high‐fat diet (HFD) were submitted to the acute exercise protocol. Transcriptomic analysis by using BXD mouse reference population database revealed that hypothalamic Tgf‐β1 mRNA is negatively correlated with genes related to thermogenesis in brown adipose tissue of BXD mice, such as peroxisome proliferator‐activated receptor gamma coactivator and is positively correlated with respiratory exchange ratio. In agreement with these results, leptin‐deficient (ob/ob) and HFD‐fed mice displayed high levels of Tgf‐β1 mRNA in the hypothalamus and reduction of Pgc1α mRNA in BAT. Interestingly, an acute exercise session reduced TGF‐β1 expression in the hypothalamus, increased Pgc1α mRNA in the BAT and reduced food consumption in obese mice. Our results demonstrated that acute physical exercise suppressed hypothalamic TGF‐β1 expression, increasing Pgc1α mRNA in BAT in obese mice.
Carboxymethyl dextran‐trimethyl chitosan coated superparamagnetic iron oxide nanoparticles: An effective siRNA delivery system for HIV‐1 Nef
Authors: Kamalzare Sara , Noormohammadi Zahra , Rahimi Pooneh , Atyabi Fatemeh , Irani Shiva , Tekie Farnaz Sadat Mirzazadeh , Mottaghitalab Fatemeh
Published: May 2019

Gene therapy, including small interfering RNA (siRNA) technology, is one of the leading strategies that help to improve the outcomes of the current therapeutic systems against HIV‐1 infection. The successful therapeutic application of siRNAs requires their safe and efficient delivery to specific cells. Here, we introduce a superparamagnetic iron oxide nanoparticle (SPION) for delivering siRNA against HIV‐1 nef (anti‐nef siRNA) into two cell lines, HEK293 and macrophage RAW 264.7. SPIONs were coated with trimethyl chitosan (TMC), and thereafter, different concentrations of SPION–TMC were coated with different ratios of a carboxymethyl dextran (CMD) to modify the physicochemical properties and improve the biological properties of the nanocarriers. The nanoparticles exhibited a spherical shape with an average size of 112 nm. The obtained results showed that the designed delivery route enhanced the uptake of siRNA into both HEK293 and RAW 264.7 cells compared with control groups. Moreover, CMD–TMC–SPIONs containing anti‐nef siRNA significantly reduced the expression of HIV‐1 nef in HEK293 stable cells. The modified siRNA‐loaded SPIONs also displayed no toxicity or apoptosis‐inducing effects on the cells. The CMD–TMC–SPIONs are suggested as potential nanocarriers for siRNA delivery in gene therapy of HIV‐1 infection.
miR‐382‐3p suppressed IL‐1β induced inflammatory response of chondrocytes via the TLR4/MyD88/NF‐κB signaling pathway by directly targeting CX43
Authors: Lei Jinlai , Fu Yahui , Zhuang Yan , Zhang Kun , Lu Daigang
Published: May 2019

miR‐382‐3p has been reported to be upregulated in synovial membrane in knee osteoarthritis (OA). Nevertheless, its role in OA remains largely unknown. The aim of this study was to investigate the specific function and mechanisms of miR‐382‐3p in the course of OA. In this study, human OA chondrocytes were pretreated with interleukin‐1β (IL‐1β) at 5 ng/ml for 12 hr to stimulate inflammatory response and matrix metalloproteinases (MMPs) expression in chondrocytes. Meanwhile, miR‐382‐3p was downregulated in IL‐1β‐stimulated chondrocytes. In addition, we found that miR‐382‐3p directly interacts with connexin 43 (CX43) and attenuates the increase of cytochrome c oxidase polypeptide II, inducible nitric oxide synthase, and MMP‐1/13 that is induced by IL‐1β. Furthermore, our observations indicated that miR‐382‐3p inhibited the expression of Toll‐like receptor 4 (TLR4), Myeloid differentiation primary response 88 (MyD88) and nuclear factor κB (NF‐κB) in IL‐1β‐stimulated chondrocytes, while CX43 overexpression could partly reverse these decreases. In conclusion, miR‐382‐3p participated in OA may through the TLR4/MyD88/NF‐κB signaling pathway by directly targeting CX43.