bluuebunny/crossref_metadata_2025 huggingface dataset:
Applications of online integrated system for coal and gas outburst prediction: A case study of Xinjing Mine in Shanxi, China
Authors: Zhao Xusheng , Sun Haitao , Cao Jie , Ning Xiaoliang , Liu Yanbao
Published: February 2020

In this study, an indicator model and system for coal and gas outburst prediction are identified and established based on gas geological anomalies, mining stress, and gas emission characteristics. In this regard, the coal and gas outburst prevention techniques and mine rules in China are taken into account. In addition, using this model, an online integrated system and database for coal and gas outburst prediction were built for Xinjing Mine in Shanxi Province. The application results of the prediction system indicate that the system software and hardware can guarantee early warning of coal and gas outburst. The system is continuous and stable, and the early warning results are issued in a timely and accurate manner. The accuracy of the early warning results is high and consistent with the actual risk of the mine.
Quantification of contemporary storm‐induced boulder transport on an intertidal shore platform using radio frequency identification technology
Authors: Hastewell Linley , Inkpen Robert , Bray Malcolm , Schaefer Martin
Published: February 2020

Extreme storm events are known to produce, entrain, transport and deposit sizable boulders along rocky coastlines. However, the extent to which these processes occur under moderate, fetch‐limited wave conditions is seldom considered. In this study we quantify boulder transport at a relatively sheltered location subject to high‐frequency, low‐magnitude storm activity. This was achieved by deploying radio frequency identification (RFID) tags within 104 intertidal limestone boulders ranging in size from fine to very coarse (intermediate axis: 0.27–2.85 m). The study was conducted over 3 years (July 2015–July 2018) and encompassed numerous storm events. Tagged boulders were relocated during 17 field surveys and their positions recorded using a differential global positioning navigation satellite system (DGNSS).

On completion, we identified boulder displacement in 69% of the tagged array. The accrued boulder transport distance amounted to 233.0 m from 195 incidents of displacement, including the movement of a boulder weighing an estimated 11.9 t. Transport was not confined to autumn and winter storms alone, as displacement was also recorded during summer months (April–September), despite the seasonally reduced wave magnitude.

Boulder production by wave quarrying was documented in three tagged clasts, confirming observations that the shore platform is actively eroding. Incidents of overturning during transport were also recorded, including multiple overturning of clasts weighing up to 5 t. We further identify a statistically significant difference (maximum p‐value ≤ 0.03) between the transport distances attributed to constrained and unconstrained boulders, suggesting that the pre‐transport morphological setting exerts considerable control over boulder transport potential.

The findings establish low to moderate storm waves as a key component in the evolution of the study site. More broadly, we claim that high‐frequency, low‐magnitude storms regularly modify these overlooked rocky coastal locations, suggesting that the hydrodynamic capability at such sites may previously have been underestimated. © 2020 John Wiley & Sons, Ltd.
Property Estimation of Per- and Polyfluoroalkyl Substances: A Comparative Assessment of Estimation Methods
Authors: Lampic Alina , Parnis J. Mark
Published: February 2020

To accurately predict the environmental fate of per- and polyfluoroalkyl substances (PFAS), high-quality physicochemical property data are required. Because such data are often not available from experiments, assessment of the accuracy of existing property estimation models is essential. The quality of predicted physicochemical property data for a set of 25 PFAS was examined using COSMOtherm, EPI Suite, the estimation models accessible through the US Environmental Protection Agency's CompTox Chemicals Dashboard, and Linear Solvation Energy Relationships (LSERs) available through the UFZ-LSER Database. The results showed that COSMOtherm made the most accurate acid dissociation constant and air–water partition ratio estimates compared with literature data. The OPEn structure-activity/property Relationship App (OPERA; developed through the CompTox Chemicals Dashboard) estimates of vapor pressure and dry octanol–air partition ratios were the most accurate compared with other models of interest. Wet octanol–water partition ratios were comparably predicted by OPERA and EPI Suite, and the organic carbon soil coefficient and solubility were well predicted by OPERA and COSMOtherm. Acid dissociation of the perfluoroalkyl acids has a significant impact on their physicochemical properties, and corrections for ionization were included where applicable. Environ Toxicol Chem 2020;39:775–786. © 2020 SETAC
Transformer anomaly detection based on time‐frequency domain software‐hardware cooperative analysis
Authors: Liu Tianyang , Zhu Yongxin , Wang Hui , Balamurugan Balusamy , Vijayakumar Pandi , Peng Jingtong
Published: February 2020

Large power transformer is one of the most important equipment in power system, while conventional methods of transformer vibration anomaly detection are inaccurate and complex. Based on the fast‐growing Internet of Energy (IoE), we put forward an improved transformer anomaly detection method that makes contributions in following ways: we first propose a new anomaly detection algorithm that combines time‐frequency domain analysis and artificial intelligence technology. Compared with the conventional modeling analysis, our method is simpler, more effective, and more adaptable. Then, we design a software‐hardware collaboration architecture and implement the algorithm on Xilinx Zynq‐7000 System on Chip (SoC) XC7Z010 development board, showing high accuracy of 98.12%. Finally, we apply the whole system to IoE environment.
Recognition of grey hole attacks in wireless sensor networks using fuzzy logic in IoT
Authors: Ye Qian , Wang Yufei , Xi Maolong , Tang Yulan
Published: February 2020

Since the devices in Internet of Things (IoT) are always interconnected with a stable Internet connection, they are prone to attacks. In the grey hole attack, a malicious node acts as a central controller to obtain data from all the nodes and it drops and alters the data packets as per its wish. In this way, the grey hole attack alters the core concept of the IoT, which enables different devices to communicate with each other. To prevent the grey hole attack and enable efficient communication between the IoT devices, a fuzzy concept is introduced in this article. Previous methods have not proficient in spotting uncountable kinds of grey hole attacks. The fuzzy engine identifies the suspicious activity that takes place in the network by the rules generated and identifies the malicious node and stops its function immediately. The simulation experimentation is carried out for accuracy, delay, energy consumption, packet delivery ratio and throughput, and the simulation contrasts with the proposed algorithm, analog behavioral modeling (ABM), and other previous techniques. The proposed system provides an accuracy rate of 45%, a packet delivery ratio of 78%, and reduced energy consumption of 35.6% compared to the previous ABM approach. Simulation outputs showed that the proposed fuzzy grey detection technique is a proficient scheme for detecting grey hole attacks and improving network capability.
Resource heterogeneity and the evolution of public goods cooperation
Authors: Stilwell Peter , O'Brien Siobhan , Hesse Elze , Lowe Chris , Gardner Andy , Buckling Angus
Published: February 2020

Heterogeneity in resources is a ubiquitous feature of natural landscapes affecting many aspects of biology. However, the effect of environmental heterogeneity on the evolution of cooperation has been less well studied. Here, using a mixture of theory and experiments measuring siderophore production by the bacterium Pseudomonas aeruginosa as a model for public goods based cooperation, we explore the effect of heterogeneity in resource availability. We show that cooperation in metapopulations that were spatially heterogeneous in terms of resources can be maintained at a higher level than in homogeneous metapopulations of the same average resource value. The results can be explained by a positive covariance between fitness of cooperators, population size, and local resource availability, which allowed cooperators to have a disproportionate advantage within the heterogeneous metapopulations. These results suggest that natural environmental variation may help to maintain cooperation.
An inverse problem formulation of the immersed‐boundary method
Authors: Yan Jianfeng , Hicken Jason E.
Published: February 2020

We formulate the immersed‐boundary method (IBM) as an inverse problem. A control variable is introduced on the boundary of a larger domain that encompasses the target domain. The optimal control is the one that minimizes the mismatch between the state and the desired boundary value along the immersed target‐domain boundary. We begin by investigating a naïve problem formulation that we show is ill‐posed: in the case of the Laplace equation, we prove that the solution is unique, but it fails to depend continuously on the data; for the linear advection equation, even solution uniqueness fails to hold. These issues are addressed by two complimentary strategies. The first strategy is to ensure that the enclosing domain tends to the true domain, as the mesh is refined. The second strategy is to include a specialized parameter‐free regularization that is based on penalizing the difference between the control and the state on the boundary. The proposed inverse IBM is applied to the diffusion, advection, and advection‐diffusion equations using a high‐order discontinuous Galerkin discretization. The numerical experiments demonstrate that the regularized scheme achieves optimal rates of convergence and that the reduced Hessian of the optimization problem has a bounded condition number, as the mesh is refined.
The effect of antifungal extracts on the contamination of grain with microfungi
Authors: Keriene Ilona , Mankeviciene Audrone , Blazyte Jaune
Published: February 2020

The study aimed to analyze the effects of extracts made from buckwheat grain, hulls, and bee products (propolis, bread, and pollen) and extraction solvents on the growth of microfungi on a medium and on buckwheat, wheat, oat, and maize grain. Research findings suggest that bioactive compounds contained in buckwheat grain reduced the amount of Fusarium spp. in the grain kept in the antifungal extract for 90 min at 25°C temperature. Buckwheat hull extract was more effective in inhibiting mycelial growth of mycotoxin‐producing Fusarium culmorum and Fusarium graminearum compared with buckwheat grain extract (13%–50% and 14%–36%, respectively). The antifungal activity of extracts of bee products did not depend on the content of phenolic compounds in them; however, it depended on the grain species treated. After treatment of oat, wheat, and maize grain with bee product extracts, the lowest concentration of microfungi was identified on oat grain. More significant analysis results were obtained for the samples where ethanol solvent had been used for the preparation of extracts.
PDK4‐Deficiency Reprograms Intrahepatic Glucose and Lipid Metabolism to Facilitate Liver Regeneration in Mice
Authors: Zhao Yulan , Tran Melanie , Wang Li , Shin Dong‐Ju , Wu Jianguo
Published: February 2020

Liver regeneration requires intrahepatic and extrahepatic metabolic reprogramming to meet the high hepatic bioenergy demand for liver cell repopulation. This study aims to elucidate how pyruvate dehydrogenase kinase 4 (PDK4), a critical regulator of glucose and lipid metabolism, coordinates metabolic regulation with efficient liver growth. We found that hepatic Pdk4 expression was elevated after two‐thirds partial hepatectomy (PHx). In Pdk4
−/− PHx mice, the liver/body weight ratio was more rapidly restored, accompanied by more aggressive hepatic DNA replication; however, Pdk4
−/− mice developed more severe hypoglycemia. In Pdk4
−/− PHx livers, the pro‐regenerative insulin signaling was potentiated, as demonstrated by early peaking of the phosphorylation of insulin receptor, more remarkable induction of the insulin receptor substrate proteins, IRS1 and IRS2, and more striking activation of Akt. The hepatic up‐regulation of CD36 contributed to the enhanced transient regeneration‐associated steatosis in Pdk4
−/− PHx mice. Notably, CD36 overexpression in mice promoted the recovery of liver/body weight ratio and elevated intrahepatic adenosine triphosphate after PHx. CD36 expression was transcriptionally suppressed by FOXO1 (forkhead box protein O1), which was stabilized and translocated to the nucleus following AMPK (adenosine monophosphate–activated protein kinase) activation. PHx remarkably induced AMPK activation, which became incompetent to respond in Pdk4
−/− livers. Moreover, we defined that PDK4‐regulated AMPK activation directly depended on intracellular adenosine monophosphate in vitro and in regenerative livers. Conclusion: PDK4 inhibition reprograms glucose and lipid metabolism to promote liver regeneration by enhancing hepatic insulin/Akt signaling and activating an AMPK/FOXO1/CD36 regulatory axis of lipid. These findings may lead to potential therapeutic strategies to prevent hepatic insufficiency and liver failure.
Assessing the validity of eyelid parameters to detect impairment due to benzodiazepines
Authors: Wilkinson Vanessa E. , Jackson Melinda L. , Westlake Justine , Stevens Bronwyn , Barnes Maree , Cori Jennifer , Swann Philip , Howard Mark E.
Published: February 2020

Objective

Benzodiazepines impair driving ability and psychomotor function. Eyelid parameters accurately reflect drowsiness; however, the effects of benzodiazepines on these measures have not been extensively studied. The aim of this study was to investigate the effect of benzodiazepines on eyelid parameters and evaluate their accuracy for detecting psychomotor impairment.

Methods

Eyelid parameters were recorded during a psychomotor vigilance task (PVT) and driving simulation over 2 days, baseline, and after 20‐mg oral temazepam. The utility of eyelid parameters for detecting PVT lapses was evaluated using receiver operating characteristic curves, and cut‐off levels indicating impairment (≥1 and ≥2 PVT lapses per min) were identified. The accuracy of these cut‐off levels for detecting driving simulator crashes was then examined.

Results

PVT and driving simulator performance was significantly impaired following benzodiazepine administration (p < .05). Average eyelid closure duration (inter‐event duration) was a reliable indicator of PVT lapses (area under the curve [AUC] of 0.87–0.90). The cut‐off value of eyelid closure duration derived from PVT AUC was able to predict driving simulator crashes with moderately high sensitivity and specificity (76.23% and 75.00%).

Conclusions

Eyelid parameters were affected by benzodiazepines and accurately detected the psychomotor impairment. In particular, eyelid closure duration is a promising real‐time indicator of benzodiazepine impairment.
Lung cancer incidence in young women vs. young men: A systematic analysis in 40 countries
Authors: Fidler‐Benaoudia Miranda M. , Torre Lindsey A. , Bray Freddie , Ferlay Jacques , Jemal Ahmedin
Published: February 2020

Previous studies have reported converging lung cancer rates between sexes. We examine lung cancer incidence rates in young women vs. young men in 40 countries across five continents. Lung and bronchial cancer cases by 5‐year age group (ages 30–64) and 5‐year calendar period (1993–2012) were extracted from Cancer Incidence in Five Continents. Female‐to‐male incidence rate ratios (IRRs) and 95% confidence intervals (95%CIs) were calculated by age group and birth cohort. Among men, age‐specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men. As a result, the female‐to‐male IRRs increased among recent birth cohorts, with IRRs significantly greater than unity in Canada, Denmark, Germany, New Zealand, the Netherlands and the United States. For example, the IRRs in ages 45–49 year in the Netherlands increased from 0.7 (95% CI: 0.6–0.8) to 1.5 (95% CI: 1.4–1.7) in those born circa 1948 and 1963, respectively. Similar patterns, though nonsignificant, were found in 23 additional countries. These crossovers were largely driven by increasing adenocarcinoma incidence rates in women. For those countries with historical smoking data, smoking prevalence in women approached, but rarely exceeded, those of men. In conclusion, the emerging higher lung cancer incidence rates in young women compared to young men is widespread and not fully explained by sex differences in smoking patterns. Future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.
Iron intake, oxidative stress‐related genes and breast cancer risk
Authors: Chang Vicky C. , Cotterchio Michelle , Bondy Susan J. , Kotsopoulos Joanne
Published: February 2020

Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress‐related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population‐based case–control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER–/PR– breast cancer risk (all ptrend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR>18 vs. 0 mg/day = 0.68, 95% CI: 0.51–0.91), and dietary heme iron was associated with an increased risk, particularly the ER–/PR– subtype (ORhighest vs. lowest quintile = 1.69, 95% CI: 1.16–2.47; ptrend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (pinteraction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity.
Oxidative stress and inflammation: Early predictive indicators of multiple recurrent coronary in‐stent chronic total occlusions in elderly patients after coronary stenting
Authors: Li Xia , Zhou Hualan , Guo Dianxuan , Hu Youdong , Fang Xiang , Chen Ying , Zhang Fenglin
Published: February 2020

Pro‐inflammatory responses and oxidative stress damages, and effects of the reduced anti‐oxidation and anti‐inflammation were involved in development and progression of coronary heart disease. We tried to identify the effects of pro‐inflammatory and oxidative stress biomarkers as well as anti‐oxidant and anti‐inflammatory factors on multiple recurrent coronary in‐stent chronic total occlusions in elderly patients after coronary stenting. We determined the expression levels of endothelial progenitor cell (EPC), stromal cell‐derived factor‐1α (SDF‐1α), vascular endothelial growth factor (VEGF), nitric oxide (NO), toll‐like receptor 2 (TLR2), toll‐like receptor 3 (TLR3), toll‐like receptor 4 (TLR4), and soluble ST2 (sST2) in elderly patients with multiple recurrent coronary in‐stent chronic total occlusions after coronary stenting. The levels of EPC, SDF‐1α, VEGF, and NO were decreased in elderly patients with multiple recurrent coronary in‐stent chronic total occlusions (p < .001). The levels of TLR2, TLR3, TLR4, and sST2 were increased in elderly patients with multiple recurrent coronary in‐stent chronic total occlusions (p < .001). The oxidative stress damages and pro‐inflammatory responses played the crucial roles in multiple recurrent coronary in‐stent chronic total occlusions of elderly patients after coronary stent placement. The levels of TLR2, TLR3, TLR4, and sST2, and the expressions of EPC, SDF‐1α, VEGF, and NO could be considered as potential early predictive indicators for multiple recurrent coronary in‐stent chronic total occlusions in elderly patients after coronary stent implantation.
Hyaluronic acid–heparin conjugated decellularized human great saphenous vein patches decrease neointimal thickness
Authors: Bai Hualong , Wang Zhiwei , Li Mingxing , Liu Yuanfeng , Wang Wang , Sun Peng , Wei Shunbo , Wang Zhiju , Li Jiang'an , Dardik Alan
Published: February 2020

Although the science of implantable materials has advanced therapeutic options in vascular surgery, graft failure is still a problem in need of a durable solution. With the development of coating and decellularization techniques, coated prosthetic grafts have become an option; however, whether decellularized human saphenous vein can be conjugated and implanted is not known. Human great saphenous vein (GSV) was harvested and decellularized and hyaluronic acid (HA)–heparin was conjugated to the GSV; water contact angles (WCA), morphology, and sulfur element change were measured before and after heparin bonding. GSV patches were implanted into the rat inferior vena cava and aorta; patches were harvested (Day 14) and analyzed. HA–heparin was successfully conjugated to the decellularized human GSV with altered morphology and reduced WCA. The HA–heparin coated decellularized GSV patch was anti‐thrombotic in vitro, and significantly decreased neointimal thickness both in patch venoplasty and angioplasty in a rat model. Both CD90 and nestin positive cells participated in neointima formation. These data show that HA–heparin coated human GSV patches decrease neointimal thickness when used both in venoplasty and arterioplasty. Tissue engineered decellularized human GSV is a promising vascular prosthesis.
Estimation of Long‐Term Efficacy of Denosumab Treatment in Postmenopausal Women With Osteoporosis: A FRAX‐ and Virtual Twin‐Based Post Hoc Analysis From the FREEDOM and FREEDOM Extension Trials
Authors: Siris Ethel , McDermott Michele , Pannacciulli Nicola , Miller Paul D , Lewiecki E Michael , Chapurlat Roland , Jódar‐Gimeno Esteban , Huang Shuang , Kanis John A
Published: February 2020

The 3‐year placebo‐controlled FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis Every 6 Months) trial established the antifracture efficacy of denosumab in postmenopausal women with osteoporosis. The 7‐year open‐label extension demonstrated that denosumab treatment for up to 10 years was associated with low rates of adverse events and low fracture incidence. The extension lacked a long‐term control group, thus limiting the ability to fully evaluate long‐term efficacy. This analysis provides a quantitative estimate of the long‐term antifracture efficacy of denosumab based on two approaches: comparison with FRAX®‐ (Fracture Risk Assessment Tool‐) and virtual twin‐estimated 10‐year fracture rates. Subjects who were randomized to denosumab in the FREEDOM trial, continued into the Extension study, completed the 10‐year visit, and missed ≤1 dose in the FREEDOM trial and ≤1 dose in the Extension (n = 1278) were included in the analysis. The 10‐year observed cumulative incidence of major osteoporotic fracture (MOF) and hip fractures was compared with the 10‐year fracture probability predicted at baseline by FRAX, a computer‐based fracture risk algorithm, and with that estimated for a hypothetical cohort of 10‐year placebo controls (virtual twins). The observed 10‐year fracture incidence was lower than the 10‐year probability predicted by FRAX for both MOF (10.75% [95% CI, 9.05 to 12.46] versus 15.63% [95% CI, 15.08 to 16.18], respectively), and hip fractures (1.17% [95% CI, 0.58 to 1.76] versus 5.62% [95% CI, 5.28 to 5.97], respectively). The observed fracture incidence was also lower than the fracture rate estimated in a hypothetical cohort of 10‐year placebo controls for MOF (23.13% [95% CI, 17.76 to 28.87]; relative risk 0.49 [95% CI, 0.36 to 0.64]). These data support the long‐term efficacy of denosumab in reducing MOF and hip fractures in postmenopausal women with osteoporosis. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Isolated Cyclic Loading During Adolescence Improves Tibial Bone Microstructure and Strength at Adulthood
Authors: Mustafy Tanvir , Londono Irène , Moldovan Florina , Villemure Isabelle
Published: February 2020

Bone is a unique living tissue, which responds to the mechanical stimuli regularly imposed on it. Adolescence facilitates a favorable condition for the skeleton that enables the exercise to positively influence bone architecture and overall strength. However, it is still dubious for how long the skeletal benefits gained in adolescence is preserved at adulthood. The current study aims to use a rat model to investigate the effects of in vivo low‐ (LI), medium‐ (MI), and high‐ (HI) intensity cyclic loadings applied during puberty on longitudinal bone development, morphometry, and biomechanics during adolescence as well as at adulthood. Forty‐two young (4‐week‐old) male rats were randomized into control, sham, LI, MI, and HI groups. After a 5 day/week for 8 weeks cyclic loading regime applied on the right tibia, loaded rats underwent a subsequent 41‐week, normal cage activity period. Right tibias were removed at 52 weeks of age, and a comprehensive assessment was performed using μCT, mechanical testing, and finite element analysis. HI and MI groups exhibited reduced body weight and food intake at the end of the loading period compared with shams, but these effects disappeared afterward. HI cyclic loading increased BMD, bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular spacing after loading. All loading‐induced benefits, except BMD, persisted until the end of the normal cage activity period. Moreover, HI loading induced enhanced bone area, periosteal perimeter, and moment of inertia, which remained up to the 52nd week. After the normal cage activity at adulthood, the HI group showed increased ultimate force and stress, stiffness, postyield displacement and energy, and toughness compared with the sham group. Overall, our findings suggest that even though both trabecular and cortical bone drifted through age‐related changes during aging, HI cyclic loading performed during adolescence can render lifelong benefits in bone microstructure and biomechanics. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Targeted Reduction of Senescent Cell Burden Alleviates Focal Radiotherapy-Related Bone Loss
Authors: Chandra Abhishek , Lagnado Anthony B , Farr Joshua N , Monroe David G , Park Sean , Hachfeld Christine , Tchkonia Tamar , Kirkland James L , Khosla Sundeep , Passos João F , Pignolo Robert J
Published: February 2020

Clinical radiotherapy treats life-threatening cancers, but the radiation often affects neighboring normal tissues including bone. Acute effects of ionizing radiation include oxidative stress, DNA damage, and cellular apoptosis. We show in this study that a large proportion of bone marrow cells, osteoblasts, and matrix-embedded osteocytes recover from these insults only to attain a senescent profile. Bone analyses of senescence-associated genes, senescence-associated beta-galactosidase (SA-β-gal) activity, and presence of telomere dysfunction-induced foci (TIF) at 1, 7, 14, 21, and 42 days post–focal radiation treatment (FRT) in C57BL/6 male mice confirmed the development of senescent cells and the senescence-associated secretory phenotype (SASP). Accumulation of senescent cells and SASP markers were correlated with a significant reduction in bone architecture at 42 days post-FRT. To test if senolytic drugs, which clear senescent cells, alleviate FRT-related bone damage, we administered the senolytic agents, dasatinib (D), quercetin (Q), fisetin (F), and a cocktail of D and Q (D+Q). We found moderate alleviation of radiation-induced bone damage with D and Q as stand-alone compounds, but no such improvement was seen with F. However, the senolytic cocktail of D+Q reduced senescent cell burden as assessed by TIF+ osteoblasts and osteocytes, markers of senescence (p16 Ink4a and p21), and key SASP factors, resulting in significant recovery in the bone architecture of radiated femurs. In summary, this study provides proof of concept that senescent cells play a role in radiotherapy-associated bone damage, and that reduction in senescent cell burden by senolytic agents is a potential therapeutic option for alleviating radiotherapy-related bone deterioration. © 2020 American Society for Bone and Mineral Research.
Embelin impact on paraquat‐induced lung injury through suppressing oxidative stress, inflammatory cascade, and MAPK/NF‐κB signaling pathway
Authors: SreeHarsha Nagaraja
Published: February 2020

The current examination was intended to observe the defensive impacts of embelin against paraquat‐incited lung damage in relationship with its antioxidant and anti‐inflammatory action. Oxidative stress marker, like malondialdehyde (MDA), antioxidative enzymes, for example, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH Px), inflammatory cytokines, such as interleukin‐1β (IL‐1β), tumor necrosis factor‐α, and IL‐6, histological examination, and nuclear factor kappa B/mitogen‐activated protein kinase (NF‐κB/MAPK) gene expression were evaluated in lung tissue. Embelin treatment significantly decreased MDA and increased SOD, CAT, and GSH Px. Embelin significantly reduced levels of inflammatory cytokines in paraquat‐administered and paraquat‐intoxicated rats. In addition, embelin suggestively decreased relative protein expression of nuclear NF‐κB p65, p‐NF‐κBp65, p38 MAPK, and p‐p38 MAPKs in paraquat‐intoxicated rats. The outcomes show the impact of embelin inhibitory action on NF‐κB and MAPK and inflammatory cytokines release, and the decrease of lung tissue damage caused by paraquat.
Paroxetine modulates immune responses by activating a JAK2/STAT3 signaling pathway
Authors: Kabiri Mahdieh , Hemmatpour Anahid , Zare Fatemeh , Hadinedoushan Hossein , Karimollah Alireza
Published: February 2020

Paroxetine, a representative of serotonin reuptake inhibitors, has recently gained attention due to its anti‐inflammatory properties. However, underlying mechanisms responsible for its immunosuppressive effects remain to be unveiled. To understand the responsible signaling mechanisms, we examined paroxetine's effect on the Janus kinase 2‐signal transducer and activator of transcription 3 (JAK2‐STAT3) signaling pathway on lipopolysaccharide + phytohemagglutinin‐induced human peripheral blood mononuclear cells culture. We also evaluate the possible dependency of paroxetine immunomodulation effects on the 5‐HT system of immune cells. Our results indicated that paroxetine attenuates proinflammatory cytokine production (interleukin‐1β [IL‐1β], IL‐17, and tumor necrosis factor‐α) and increases expression of IL‐10 and JAK2/STAT3 evidence for macrophages polarization to M2 subset and functional dendritic cells depletion. In conclusion, paroxetine can exert its anti‐inflammatory effects via both the 5‐HT systems present in immune cells and the JAK2‐STAT3 pathway. Our results also suggest that paroxetine exerted its immunosuppressive effects partially via serotonin. Nonetheless, JAK2/STAT3‐modulated paroxetine effects were independent of serotonin, hence sufficiently applicable for inflammation repression.
Circular RNA circMAN2B2 promotes growth and migration of gastric cancer cells by down‐regulation of miR‐145
Authors: Sun Bo , Sun Haiyuan , Wang Qunying , Wang Xinhong , Quan Jingzi , Dong Dongfang , Lun Yue
Published: February 2020

Background

CircMAN2B2 is a newly discovered circRNA that has been found to be an oncogene in lung cancer and glioma. The present study was designed to reveal the role of circMAN2B2 in gastric carcinoma (GC).

Methods

qRT‐PCR method was utilized to examine circMAN2B2 expression in GC tissues and paracancerous tissues. Next, circMAN2B2 expression in SNU‐16 and AGS cells was silenced by transfection. CCK‐8 assay, colony formation assay, flow cytometer, Transwell assay, and Western blot were conducted for testing cell phenotype changes. Further, the downstream genes and signaling were uncovered by qRT‐PCR and Western blot.

Results

As relative to paracancerous tissues, circMAN2B2 was high‐expressed in GC tissues. Silence of circMAN2B2 clearly declined SNU‐16 and AGS cells viability, survival, migration but enhanced apoptosis. Meanwhile, silence of circMAN2B2 induced the cleavage of caspases (−3 and −9), down‐regulation of MMPs (−2 and −9), and up‐regulation of miR‐145. The impacts of circMAN2B2 silence toward SNU‐16 and AGS cells were attenuated by miR‐145 silence. Moreover, circMAN2B2 silence deactivated PI3K, AKT while activated JNK through regulating miR‐145.

Conclusion

This work presented the oncogenic function of circMAN2B2 in GC cells growth and migration. CircMAN2B2 exerted its function possibly through regulating miR‐145 as well as PI3K/AKT and JNK pathways.
Perceived acceptability of wearable devices for the treatment of mental health problems
Authors: Hunkin Hugh , King Daniel L. , Zajac Ian T.
Published: February 2020

Objective

This study examined the potential acceptability of wearable devices (e.g., smart headbands, wristbands, and watches) aimed at treating mental health disorders, relative to conventional approaches.

Methods

A questionnaire assessed perceptions of wearable and nonwearable treatments, along with demographic and psychological information. Respondents (N = 427) were adults from a community sample (Mage = 44.6, SDage = 15.3) which included current (30.2%) and former (53.9%) mental health help‐seekers.

Results

Perceived effectiveness of wearables was a strong predictor of interest in using them as adjuncts to talk therapies, or as an alternative to self‐help options (e.g., smartphone applications). Devices were more appealing to those with negative evaluations of psychological therapy and less experience in help‐seeking.

Conclusions

Interest in using wearable devices was strong, particularly when devices were seen as effective. Clients with negative attitudes to conventional therapies may be more responsive to using wearable devices as a less directive treatment approach.
Male fertility in Mus musculus requires the activity of TRYX5 in sperm migration into the oviduct
Authors: Zhang Haihang , Li Yushan , Cui Kuiqing , Chen Xiu , Shang Cuiling , Min Wanping , Jin Peng , Jiang Zhaodi , Shi Deshun , Liu Qingyou , Wang Fengchao
Published: February 2020

Nowadays, abnormal loss of serine proteases appears very frequently in male patients with unexplained sterility. In fact, many testis‐specific serine proteases, the largest family among the four protease families implicated in murine spermatogenesis, are indispensable for reproduction. In the present study, we demonstrate that the previously uncharacterized testis‐specific serine protease TRYX5 (1700074P13Rik) is required for male fertility in mice. Tryx5−/− male mice are sterile, yet they have normal spermatogenesis and normal sperm parameters. In vivo fertilization experiments showed that the fertilization rate of Tryx5−/− sperm was almost zero. Sperm counting and analysis of paraffin sections of oviducts revealed that Tryx5−/− sperm were unable to migrate into the oviduct, which is likely the cause of the observed infertility of the Tryx5−/− male mice. Importantly, we also found that there was almost no mature ADAM3 present in Tryx5−/− sperm and almost no ADAM3 precursor in Tryx5−/− elongated spermatids of S13‐16 stage, even though testes of Tryx5−/− and wild type mice had the same amount of the total precursor ADAM3. Collectively, our results demonstrate that Tryx5 is essential for male fertility in mice and suggest that TRYX5 functions in the stability or localization of ADAM3 precursor in elongated spermatids S13‐16 stage, thereby regulating the ability of sperm to migrate from the uterus into the ampulla of the oviduct, the site of fertilization.
miRNA‐mediated macrophage behaviors responding to matrix stiffness and ox‐LDL
Authors: Li Jing , Wang Sufang , Li Yuhui , Zhang Nu , Gribskov Michael , Zhang Xi , Lin Min , Shao Dongyan , Zhang Chen , Dai Liangliang , Qin Chuanguang , Duan Xianglong , Li Juntang , Xu Feng , Yang Hui
Published: February 2020

Atherosclerosis is one of the leading causes of morbidity and mortality, mainly due to the immune response triggered by the recruitment of monocytes/macrophages in the artery wall. Accumulating evidence have shown that matrix stiffness and oxidized low‐density lipoproteins (ox‐LDL) play important roles in atherosclerosis through modulating cellular behaviors. However, whether there is a synergistic effect for ox‐LDL and matrix stiffness on macrophages behavior has not been explored yet. In this study, we developed a model system to investigate the synergistic role of ox‐LDL and matrix stiffness on macrophage behaviors, such as migration, inflammatory and apoptosis. We found that there was a matrix stiffness‐dependent behavior of monocyte‐derived macrophages stimulated with ox‐LDL. What's more, macrophages were more sensitive to ox‐LDL on the stiff matrices compared to cells cultured on the soft matrices. Through next‐generation sequencing, we identified miRNAs in response to matrix stiffness and ox‐LDL and predicted pathways that showed the capability of miRNAs in directing macrophages fates. Our study provides a novel understanding of the important synergistic role of ox‐LDL and matrix stiffness in modulating macrophages behaviors, especially through miRNAs signaling pathways, which could be potential key regulators in atherosclerosis and immune‐targeted therapies.
Long noncoding RNA TCL6 binds to miR‐106a‐5p to regulate hepatocellular carcinoma cells through PI3K/AKT signaling pathway
Authors: Luo Li‐Hua , Jin Min , Wang Lan‐Qing , Xu Guo‐Jie , Lin Zhen‐Yu , Yu Dan‐Dan , Yang Sheng‐Li , Ran Rui‐Zhi , Wu Gang , Zhang Tao
Published: February 2020

Long noncoding RNAs (lncRNAs) have been reported to dysregulate and involve in the pathology of hepatocellular carcinoma (HCC). Nonetheless, the functional role of lncRNA T cell leukemia/lymphoma 6 (TCL6) and its underlying mechanism in HCC remain unclear. Herein, we analyzed the expression of TCL6 and elucidated its mechanistic involvement in HCC. Bioinformatics analyses indicated TCL6 was evidently downregulated in HCC tissues compared with normal controls. TCL6 was downregulated while microRNA‐106a‐5p (miR‐106a‐5p) was upregulated in HCC cell lines. Moreover, knockdown or overexpression of TCL6 significantly raised or diminished the expression level of miR‐106a‐5p in HCC cells, similar to the effect of miR‐106a‐5p on TCL6 expression. Functionally, TCL6 inhibited the proliferative, migratory, and invasive potentials of HCC cells as analyzed by cell counting kit‐8, scratch wound healing, and transwell assays, respectively. Conversely, miR‐106a‐5p exerted an opposite effect on the proliferative, migratory, and invasive potentials of HCC. RNA immune precipitation and luciferase reporter assays revealed TCL6 directly bound to miR‐106a‐5p and luciferase reporter assay verified phosphatase and tensin homolog (PTEN) was a target gene of miR‐106a‐5p. Mechanistically, TCL6 knockdown evidently reduced PTEN expression at both messenger RNA and protein levels, and miR‐106a‐5p inhibitor partially rescued this reduction effect in HCC cells. Additionally, western blot assays demonstrated miR‐106a‐5p downregulation or TCL6 overexpression promoted the protein level of PTEN, and suppressed the phosphorylation level of AKT, the protein level of phosphatidylinositol 3‐kinase (PI3K). Collectively, these results revealed TCL6 as a tumor‐suppressive lncRNA regulates PI3K/AKT signaling pathway via directly binding to miR‐106a‐5p in HCC. This mechanism provides a theoretical basis for HCC pathogenesis and a potential therapeutic strategy for HCC treatment.
The therapeutic effect of bone marrow–derived mesenchymal stem cells on osteoarthritis is improved by the activation of the KDM6A/SOX9 signaling pathway caused by exposure to hypoxia
Authors: Zhi Zhongzheng , Zhang Chenglin , Kang Jian , Wang Yingjie , Liu Jingdong , Wu Furong , Xu Guanghui
Published: February 2020

Abnormal expression of KDM6A and SOX9 is a key factor in the pathogenesis of osteoarthritis (OA). Cellular treatments of OA with articular cartilage chondrocytes (ACCs) and bone marrow mesenchymal stem cells (BMSCs) are promising, but their underlying mechanisms remain to be explored. The pellet size, weight and sulfated glycosaminoglycan/DNA content of ACCs were measured to evaluate the effect of BMSCs on the chondrogenic differentiation of SCCs. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to analyze the proliferation of ACCs cultured along or cocultured with BMSCs. Quantitative polymerase chain reaction (qPCR) was performed to evaluate the messenger RNA expression of KDM6A, SOX9, type2 collagen, and Aggrecan in ACCs and OA rats. Western blot and immunohistochemistry were performed to analyze the expression of KDM6A and SOX9 proteins. Bisulfite sequencing PCR was performed to assess the DNA methylation level of the SOX9 promoter. Flow cytometry was used to evaluate the apoptotic status of ACCs. The chondrogenic differentiation of ACCs was significantly enhanced by coculturing with BMSCs, especially under a hypoxic condition. The expression of KDM6A, SOX9, type2 collagen, and Aggrecan was remarkably elevated in ACCs cocultured with BMSCs. Also, the DNA methylation of SOX9 promoter was decreased in ACCs cocultured with BMSCs, along with notably reduced apoptosis. Moreover, ACCs cocultured with BMSCs could repair cartilage lesions and prevent the abnormal expression of KDM6A, SOX9, type2 collagen, and Aggrecan in OA rats. In this study, we cocultured ACCs with BMSCs and used them to treat OA rats. Our findings presented a mechanistic basis for explaining the therapeutic effect of BMSCs on OA treatment.
The Nrf2 activator MIND4‐17 protects retinal ganglion cells from high glucose‐induced oxidative injury
Authors: Chen Nan , Li Ya , Huang Nan , Yao Jin , Luo Wei‐Feng , Jiang Qin
Published: February 2020

Diabetic retinopathy (DR) is a leading cause of acquired blindness among adults. High glucose (HG) induces oxidative injury and apoptosis in retinal ganglion cells (RGCs), serving as a primary pathological mechanism of DR. MIND4‐17 activates nuclear‐factor‐E2‐related factor 2 (Nrf2) signaling via modifying one cysteine (C151) residue of Kelch‐like ECH‐associated protein 1 (Keap1). The current study tested its effect in HG‐treated primary murine RGCs. We show that MIND4‐17 disrupted Keap1–Nrf2 association, leading to Nrf2 protein stabilization and nuclear translocation, causing subsequent expression of key Nrf2 target genes, including heme oxygenase‐1 and NAD(P)H quinone oxidoreductase 1. Functional studies showed that MIND4‐17 pretreatment significantly inhibited HG‐induced cytotoxicity and apoptosis in primary murine RGCs. Reactive oxygen species production and oxidative injury in HG‐treated murine RGCs were attenuated by MIND4‐17. Nrf2 silencing (by targeted small interfering RNA) or knockout (by CRISPR/Cas9 method) abolished MIND4‐17‐induced RGC cytoprotection against HG. Additionally, Keap1 knockout or silencing mimicked and abolished MIND4‐17‐induced activity in RGCs. In vivo, MIND4‐17 intravitreal injection activated Nrf2 signaling and attenuated retinal dysfunction by light damage in mice. We conclude that MIND4‐17 activates Nrf2 signaling to protect murine RGCs from HG‐induced oxidative injury.
Protective Association Between Calcium Channel Blocker Use and Breast Cancer Recurrence in Postsurgical Women: A Population‐Based Case‐Control Study in Taiwan
Authors: Shih Jui‐Hu , Kao Li‐Ting , Chung Chi‐Hsiang , Liao Guo‐Shiou , Fann Li‐Yun , Chien Wu‐Chien , Li I‐Hsun
Published: February 2020

Neoadjuvant chemotherapy induces metastasis of residual breast cancers through activation of tumor‐associated macrophages. Previous studies have indicated that calcium channel blockers (CCBs) exert anti‐inflammatory and antimigratory effects on macrophages via attenuating Ca2+ entry into macrophages. However, no existing empirical research has addressed the relationship between previous CCB use and breast cancer recurrence. In this study, 4840 Taiwanese women aged ≥20 years with breast cancer who underwent breast surgery from January 1, 2007, to December 31, 2015, were enrolled. The date of cancer recurrence was defined as the index date. Logistic regression was performed to evaluate the relationship between previous CCB exposure and cancer recurrence among female patients who underwent surgery for breast cancer. After adjusting for demographic characteristics, comorbidities, and tumor‐node‐metastasis stage, the adjusted odds ratio (OR) for CCB exposure within 5 years before the index date in women with recurrence compared with nonrecurrent controls was 0.73 (95% confidence interval [CI], 0.53‐0.97). Further analysis revealed that the adjusted OR for CCB exposure between the surgery and index dates in women with recurrence relative to nonrecurrent controls was 0.72 (95%CI, 0.66‐0.95). In particular, prior CCB use was significantly associated with a lower risk (34%) of breast cancer recurrence among women 20 to 54 years old (OR, 0.66; 95%CI, 0.47‐0.83). This study uncovered a protective association between previous CCB use and breast cancer recurrence.
Construction of Z‐scheme Pt‐TiO2/(Er3+:Y3Al5O12@Ta2O5)/HAP and its application in sonocatalytic degradation of prometryn and disinfection of Escherichia coli
Authors: Li Guanshu , Cao Yuejiao , Yi Ludong , Wang Jun , Song Youtao
Published: February 2020

BACKGROUND

The recovery and reuse of sonocatalysts are the pivotal issues in the sonocatalytic degradation of organic pollutants. The use of some natural minerals as the carrier is not only beneficial to recycling of sonocatalysts, but also reduces the treatment costs of organic pollutants. Two kinds of hydroxyapatite (HAP), Ox Bone (OB)‐HAP and synthesized (Syn)‐HAP combine with the Pt‐TiO2/(Er3+:Y3Al5O12@Ta2O5) (P‐TET) composite, obtaining two Z‐scheme sonocatalysts, P‐TET/OB‐HAP and P‐TET/Syn‐HAP, respectively. The sonocatalytic activities of the prepared samples are investigated via degradation of prometryn and disinfection of Escherichia coli.

RESULTS

A series of characterizations showed that the Z‐scheme P‐TET/(OB or Syn)‐HAP sonocatalysts were prepared successfully. To evaluate their sonocatalytic activities, some influencing factors such as ultrasonic irradiation time, inorganic oxidants, used times and trapping agents on the sonocatalytic degradation prometryn were determined. The best degradation ratio (80.31% based on N computing and 85.07% based on S atom computing) of prometryn could be obtained for 10 mmol L−1 K2S2O8, 1.0 g L−1 P‐TET/OB‐HAP sonocatalyst and 150 min ultrasonic irradiation. The excellent sonocatalytic disinfection ratio (88.65%) of E. coli could also be obtained under 40 min ultrasound irradiation. Moreover, a possible mechanism on sonocatalytic degradation of prometryn was illustrated.

CONCLUSION

The treated bovine bone HAP was directly used as a carrier to combine with P‐TET to construct a novel Z‐scheme P‐TET/OB‐HAP sonocatalyst. The high degradation ratio of prometryn and disinfection ratio of E. coli showed that P‐TET/OB‐HAP could be a promising sonocatalyst for the degradation of organic pollutants and the disinfection of bacteria. © 2020 Society of Chemical Industry