bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic dust, causing both oxidative stress and Nrf2 activation, is phagocytized by bronchial epithelial cells
Authors: McGovern Toby , Farahnak Soroor , Chen Michael , Larsson Kjell , Martin James G. , Adner Mikael
Published: May 2019

Inhalation of organic dust (OD) from swine confinement facilities leads to pulmonary inflammation, airway hyperresponsiveness, and oxidative stress. In mice, pretreatment with a hydroxyl radical scavenger prevents airway inflammation and airway hyperresponsiveness (AHR) induced by OD exposure. We sought to determine a mechanism by which OD could induce oxidative stress in bronchial epithelial cells. Human bronchial epithelial cells (BEAS-2B or NHBE) were treated with various concentrations of OD, followed by evaluation of intracellular oxidative stress using 2′,7′–dichlorofluorescein diacetate (DCFDA). After stimulation with OD, gene expression of antioxidant genes was assessed by real-time quantitative PCR followed by quantification of Nrf2 nuclear translocation using a luciferase reporter assay. Phagocytic markers (CD36 and CD68) were analyzed by FACS. Cells were treated with an actin inhibitor, cytochalasin D, before OD exposure and evaluated for Nrf2 nuclear translocation and DCFDA. Mice were pretreated with sulforaphane, the Nrf2 activator, before OD exposure and evaluated for pulmonary inflammation and airway reactivity. OD induced a time- and concentration-dependent increase in DCFDA. mRNA expression levels of Nrf2-dependent genes and Nrf2 nuclear translocation were increased after OD exposure. OD exposure increased the expression of CD68 and CD36. Cytochalasin D prevented oxidative stress and Nrf2 nuclear translocation after OD. Pretreatment with sulforaphane prevented OD-induced inflammation and AHR while increasing the uptake of OD in bronchial epithelial cells. Bronchial epithelial cells can phagocytose OD, resulting in an increase in endogenous oxidative stress. Nrf2-dependent mechanisms mediate the antioxidant response to OD.
New mouse model of chronic kidney disease transitioned from ischemic acute kidney injury
Authors: Wei Jin , Zhang Jie , Wang Lei , Jiang Shan , Fu Liying , Buggs Jacentha , Liu Ruisheng
Published: May 2019

Acute kidney injury (AKI) significantly increases the risk of development of chronic kidney disease (CKD), which is closely associated with the severity of AKI. However, the underlying mechanisms for the AKI to CKD transition remain unclear. Several animal models with AKI to CKD transition have been generated and widely used in research; however, none of them exhibit the typical changes in glomerular filtration rate or plasma creatinine, the hallmarks of CKD. In the present study, we developed a novel model with a typical phenotype of AKI to CKD transition in C57BL/6 mice. In this model, life-threatening ischemia-reperfusion injury was performed in one kidney, whereas the contralateral kidney was kept intact to maintain animal survival; then, after 2 wk of recovery, when the renal function of the injured kidney restored above the survival threshold, the contralateral intact kidney was removed. Animals of this two-stage unilateral ischemia-reperfusion injury model with pedicle clamping of 21 and 24 min exhibited an incomplete recovery from AKI and subsequent progression of CKD with characteristics of a progressive decline in glomerular filtration rate, increase in plasma creatinine, worsening of proteinuria, and deleterious histopathological changes, including interstitial fibrosis and glomerulosclerosis. In conclusion, a new model of the AKI to CKD transition was generated in C57BL/6 mice.
Parallel modulation of interhemispheric inhibition and the size of a cortical hand muscle representation during active contraction
Authors: Turco Claudia V. , Fassett Hunter J. , Locke Mitchell B. , El-Sayes Jenin , Nelson Aimee J.
Published: May 2019

Interhemispheric inhibition (IHI) between motor cortexes is thought to suppress unwanted mirror movements during voluntary behaviors and can be assessed using paired-pulse transcranial magnetic stimulation (TMS). The magnitude of IHI may be related to the size of the cortical representation for a given muscle as a mechanism for facilitating unimanual control. To date, the relationship between IHI and cortical muscle representations remains unknown. Fifteen healthy, right-handed individuals participated in the present study. IHI was examined in the right first dorsal interosseous (FDI) muscle by delivering conditioning TMS to ipsilateral (right) primary motor cortex (M1) followed by a test TMS pulse to contralateral (left) M1. The size of the FDI representation in M1 was determined by delivering suprathreshold TMS over a 5 × 5-cm grid centered on the FDI motor hotspot of the left M1. Both IHI and cortical territory were obtained during three conditions: rest, contralateral (right) FDI contraction, and ipsilateral (left) FDI contraction. Results indicate a significant association between IHI and the size of the FDI representation only in the context of contraction and not when the FDI muscle was relaxed. Specifically, reduced IHI corresponded to larger cortical FDI representations during both contralateral and ipsilateral contraction. These data demonstrate that, for a muscle of the hand, the magnitude of IHI and the cortical territory are associated within the context of muscle contraction.

NEW & NOTEWORTHY This study provides evidence from noninvasive brain stimulation that communication between the motor cortexes of the two hemispheres plays a role in shaping the motor cortical map that outputs to a hand muscle during active contraction of that muscle. This relationship exists only when the hand muscle is contracted. The findings presented further our understanding of motor control during unilateral movement and may inform future research targeting clinical populations that exhibit impaired unilateral control.
Speed Control of PMSM Based on an Optimized ADRC Controller
Authors: Meng YiBo , Liu BingYou , Wang LiChao
Published: May 2019

Permanent‐magnet synchronous motor (PMSM) is a nonlinear, multivariate, strongly coupled system with uncertain external interference. A general control method cannot meet system requirements. This study proposes an optimal control strategy based on active disturbance rejection control (ADRC) to achieve high‐precision control of PMSM. First, interpolation fitting is used to construct a nonlinear function with improved continuity and derivative near the origin and segment points. Second, various components of active disturbance rejection control are constructed based on the new nonlinear function, which mainly improves the extended state observer and nonlinear state error feedback. Simulation results show that under similar parameters, the improved active disturbance rejection control has smaller overshoot, faster tracking capacity, and stronger anti‐interference capability compared with traditional active disturbance rejection control. Finally, the optimized active disturbance rejection control is used in the motion control system of PMSM. Experimental results show that the proposed optimal control strategy is simple and has good control performance.
Association of Lifestyle and Food Consumption with Bone Mineral Density among People Aged 50 Years and Above Attending the Hospitals of Kathmandu, Nepal
Authors: Chaudhary Narendra Kumar , Timilsena Mukti Nath , Sunuwar Dev Ram , Pradhan Pranil Man Singh , Sangroula Raj Kumar
Published: May 2019

Background. Bone mineral density (BMD) is the measure of the minerals, mostly calcium and phosphorous, contained in certain volume of bone to diagnose osteoporosis. The aim of the study was to find out the association of lifestyle and food consumption with BMD. Methods. An analytical cross-sectional study was conducted among 169 people of age 50 years and above who underwent Dual Energy X-Ray Absorptiometry (DEXA or DXA) scan in the hospitals of Kathmandu valley of Nepal. Food frequency questionnaire and 24-hour recall methods were followed. The DXA reports of the participants were observed to identify osteoporosis. Chi-square test, independent sample t-test, and binary logistic regression were applied to explore the association of BMD with different variables. Result. The prevalence of osteoporosis, osteopenia, and normal BMD was 37.3%, 38.5%, and 24.2%, respectively. The prevalence of osteoporosis increased with sex and age (AOR 3.339, CI: 1.240-8.995, p-value 0.017; AOR 3.756, CI: 1.745-8.085, p-value 0.001), respectively. Higher BMI was associated with lower odds of osteoporosis (AOR 0.428, CI: 0.209-0.877, p-value 0.020). Smoking had bad effect on the health of bone (AOR 3.848, CI: 1.179-12.558, p-value 0.026). Daily dietary calcium intake had negative association with osteoporosis with the p-value of 0.003; however, the daily consumption of vitamin D rich food had no association with osteoporosis. Conclusion. High prevalence of osteoporosis and osteopenia was found in older people. Osteoporosis was found to be significantly associated with sex, age, lower BMI, smoking habit, and daily calcium consumption. Further research can be conducted by making the relationship of calcium consumption with the numerical T-value of scanned body parts.
Features of Oxidative and Nitrosative Metabolism in Lung Diseases
Authors: Soodaeva Svetlana , Kubysheva Nailya , Klimanov Igor , Nikitina Lidiya , Batyrshin Ildar
Published: May 2019

Respiratory diseases are accompanied by intensification of free radical processes at different levels of the biological body organization. Simultaneous stress and suppression of various parts of antioxidant protection lead to the development of oxidative stress (OS) and nitrosative stress (NS). The basic mechanisms of initiation and development of the OS and NS in pulmonary pathology are considered. The antioxidant defense system of the respiratory tract is characterized. The results of the NS and OS marker study in various respiratory diseases are presented. It is shown that NS and OS are multilevel complex-regulated processes, existing and developing in inseparable connection with a number of physiological and pathophysiological processes. The study of NS and OS mechanisms contributes to the improvement of the quality of diagnosis and the development of therapeutic agents that act on different pathogenetic stages of the disease.
Dynamic Analysis of a Novel Rail‐Grinding Car Using Open‐Structured Abrasive Belt for High‐Speed Railways
Authors: Fan Wengang , Hou Guangyou , Wang Wenxi , Wu Yuefeng
Published: May 2019

Nowadays, applying rail grinding has been worldwide recognized as the routine maintenance approach to improving the wheel‐rail relationship, as well as extending the rail’s serving life. However, the traditional rail repair technology with the abrasive wheel or the milling cutter is getting harder to meet the increasing demand for high efficiency with high speed. In this paper, according to the engineering requirements and constraints, a new fast rail‐grinding car based on open‐structured belt grinding technology was designed for the corrugation treatment on high‐speed railways. A corresponding simulation model was established and its dynamic working performance was then assessed by SIMPACK software. Results of the four dynamic indices for both straight and curve tracks were within the limits, which had verified the design rationality of the new rail‐grinding car. Those dynamic indices are the lateral vibration acceleration, the vertical vibration acceleration, the axle transverse force, and the derailment coefficient.
Effects of High-Frequency Proprioceptive Training on Single Stance Stability in Older Adults: Implications for Fall Prevention
Authors: Riva Dario , Fani Mara , Benedetti Maria Grazia , Scarsini Angelo , Rocca Flavio , Mamo Carlo
Published: May 2019

Single-limb stance instability is a major risk factor for falls in older adults. Thus, improvement of stance stability could play an important role in fall prevention. This study aimed to determine whether high-frequency proprioceptive training (HPT) could significantly improve single stance stability (SSS) in older adults, by increasing proprioceptive control and optimizing the contribution of vision. Sixty-one subjects (30 men, 31 women) aged 65-85 years were investigated. The subjects were randomly assigned to three intervention groups, i.e., HPT, treadmill, and no intervention, stratifying by gender and proprioceptive control at baseline. Stability tests and HPT, consisting of 12 sessions (6 weeks), were performed with computerized postural stations. Pre-post analysis showed that HPT significantly improved SSS by increasing proprioceptive control (p<0.001) and postural control (p<0.01). The treadmill and no intervention groups did not show any significant change. The results showed that different levels of proprioceptive control may activate, inhibit, or minimize the stabilizing intervention of vision. Given that HPT significantly reduced ankle sprains and low back pain in professional athletes (previous study), we discuss the hypothesis that the risk of falls in older adults and the risk of recurrent injuries in athletes would have a common origin: lack of proprioceptive control consequent to reduced interaction with uneven ground. The findings suggest that HPT may be a powerful activator of refined proprioceptive control, which allows increased SSS, safer interaction with the ground, and mitigation of other risk factors.
Autophagy Dysfunction, Cellular Senescence, and Abnormal Immune-Inflammatory Responses in AMD: From Mechanisms to Therapeutic Potential
Authors: Wang Shoubi , Wang Xiaoran , Cheng Yaqi , Ouyang Weijie , Sang Xuan , Liu Jiahui , Su Yaru , Liu Ying , Li Chaoyang , Yang Liu , Jin Lin , Wang Zhichong
Published: May 2019

Age-related macular degeneration (AMD) is a blinding disease caused by multiple factors and is the primary cause of vision loss in the elderly. The morbidity of AMD increases every year. Currently, there is no effective treatment option for AMD. Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) is currently the most widely used therapy, but it only aims at neovascularization, which is an intermediate pathological phenomenon of wet AMD, not at the etiological treatment. Anti-VEGF therapy can only temporarily delay the degeneration process of wet AMD, and AMD is easy to relapse after drug withdrawal. Therefore, it is urgent to deepen our understanding of the pathophysiological processes underlying AMD and to identify integrated or new strategies for AMD prevention and treatment. Recent studies have found that autophagy dysfunction in retinal pigment epithelial (RPE) cells, cellular senescence, and abnormal immune-inflammatory responses play key roles in the pathogenesis of AMD. For many age-related diseases, the main focus is currently the clearing of senescent cells (SNCs) as an antiaging treatment, thereby delaying diseases. However, in AMD, there is no relevant antiaging application. This review will discuss the pathogenesis of AMD and how interactions among RPE autophagy dysfunction, cellular senescence, and abnormal immune-inflammatory responses are involved in AMD, and it will summarize the three antiaging strategies that have been developed, with the aim of providing important information for the integrated prevention and treatment of AMD and laying the ground work for the application of antiaging strategies in AMD treatment.
Novel TEM Microscopy and Electron Diffraction Techniques to Characterize Cultural Heritage Materials: From Ancient Greek Artefacts to Maya Mural Paintings
Authors: Nicolopoulos Stavros , Das Partha P. , Pérez Alejandro Gómez , Zacharias Nikolaos , Cuapa Samuel Tehuacanero , Alatorre Jesús Angel Arenas , Mugnaioli Enrico , Gemmi Mauro , Rauch Edgar F.
Published: May 2019

To understand in-depth material properties, manufacturing, and conservation in cultural heritage artefacts, there is a strong need for advanced characterization tools that enable analysis down to the nanometric scale. Transmission electron microscopy (TEM) and electron diffraction (ED) techniques, like 3D precession electron diffraction tomography and ASTAR phase/orientation mapping, are proposed to study cultural heritage materials at nanoscale. In this work, we show how electron crystallography in TEM helps to determine precise structural information and phase/orientation distribution of various pigments in cultural heritage materials from various historical periods like Greek amphorisks, Roman glass tesserae, and pre-Hispanic Maya mural paintings. Such TEM-based methods can be an alternative to synchrotron techniques and can allow distinguishing accurately different crystalline phases even in cases of identical or very close chemical compositions at the nanometric scale.
Attitude towards Antipsychotic Medications in Patients Diagnosed with Schizophrenia: A Cross-Sectional Study at Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia
Authors: Kassew Tilahun , Demilew Demeke , Birhanu Addis , Wonde Mesele , Liyew Biks , Shumet Shegaye
Published: May 2019

Background. Poor attitude towards antipsychotic drugs is high, and it is a factor for non-adherence to treatment. This increases the risk of relapse, associated healthcare utilization, and costs. This study aimed to assess attitude towards antipsychotic medication among patients with schizophrenia. Objectives. The aim of this institution based cross-sectional study was to assess attitude towards antipsychotic medications and associated factors among patients with schizophrenia who attend the outpatient clinics at Amanuel Mental Specialized Hospital, 2018. Methods. In a cross-sectional study, 393 schizophrenic patients from Amanuel Mental Specialized Hospital were recruited by a systematic random sampling technique. Drug Attitude Inventory (DAI-10) was used to assess attitude, experience, and belief about antipsychotics. Glasgow antipsychotic side effect scale modified version, positive and negative syndrome scale, and Birch wood’s insight scale for psychosis were the instruments used to assess the associated factors. Simple and multiple linear regression analysis models were fitted, and the adjusted unstandardized beta (β) coefficient at 95% confidence interval was used. Results. The mean score of attitude towards antipsychotic medications was 6.51 with standard deviation (SD) of 2.22. In multiple linear regression, positive symptoms (β= -0.07, 95% CI: (-0.09, -0.05)), negative symptoms (β= -0.04, 95% CI: (-0.06,-0.02)), shorter (≤5 years) duration of illness (β= -0.39, 95% CI: (-0.63, -0.15)), first generation antipsychotics (β = -0.35, 95% CI: (-0.55,-0.14)), having sedation (β= -0.28, 95% CI: (-0.52, -0.02)), and extra-pyramidal side effects (β= -0.34, 95% CI: (-0.59,-0.09)) were factors negatively associated with attitude towards antipsychotic medication treatment. Insight to illness (β= 0.24, 95% CI: (0.20, 0.27) was a factor positively associated with attitude towards antipsychotic medications. Conclusion. The result suggests that the mean score of participants’ attitude towards antipsychotic medications was good. Prevention of side effects particularly due to first generation antipsychotics is necessary.
Characterization of the Beekeeping Value Chain: Challenges, Perceptions, Limitations, and Opportunities for Beekeepers in Kayonza District, Rwanda
Authors: Mushonga Borden , Hategekimana Landouard , Habarugira Gervais , Kandiwa Erick , Samkange Alaster , Ernest Segwagwe Basiamisi Victor
Published: May 2019

A survey was undertaken to characterize the honey production value chain and identify the challenges, limitations, and opportunities for beekeepers in Kayonza District, Eastern Rwanda, in light of the stagnation of the apiculture industry. The majority (86%, n = 100) of the beekeepers were adult males. Most of the respondents (71%) lacked primary level education. The majority of the hives were made from hollow tree logs (40%), tree barks (12%), banana leaves/bark (11%), cow dung (8%), mud (7%), grass (6%), tree leaves (6%), and the rest (20%) were improved beehives, particularly Langstroth hives. The hive pests encountered were hive beetles (25%), small black ants (19%), wax moths (12%), lizards (8%), termites (7%), birds (6%), mites (3%), and mice (2%). Fifty-five percent of the respondents hung their hives on trees to prevent pest invasion with 95% effectiveness, 25% frequently smoked their hives with 85% effectiveness, 16% cleared the bushes around apiaries with 55% effectiveness, and 4% used traditional plant insect repellents with 35% effectiveness. Forty-one percent of the respondents lacked adequate information on beekeeping, 25% had inadequate time to work on apiaries, 24% had inadequate technical knowledge and implements, and 10% needed additional labour for managing apiaries. Based on the results of this study, beekeeping in Kayonza is still largely traditional, characterized by the use of antiquated production methods and underutilization of available marketing channels. Perceptions in the district are that beekeeping is for the poor and illiterate. Challenges and limitations of beekeeping in Kayonza District include lack of education, gender bias, pests and diseases, absconding and swarming of bees, high costs, and lack of modern apicultural equipment. However, the potential for developing beekeeping enterprise (opportunities) is immense given the abundance of wild bee populations, possibility of women participation, abundance of honey collection centres (market), and availability of technical support from Government and development agencies. In conclusion, this study advocates the need for intervention measures to educate and promote production and marketing of quality honey, tackle pest and disease for beekeepers and boost Rwanda’s apiculture industry.
MicroRNA-33-3p Regulates Vein Endothelial Cell Apoptosis in Selenium-Deficient Broilers by Targeting E4F1
Authors: Zhang Yiming , Wan Na , Pan Tingru , Hu Xueyuan , Liu Qingqing , Li Shu
Published: May 2019

Selenium (Se) is a type of nutrient element. The tissues of organisms can have pathological damage, including apoptosis, due to Se deficiency. Apoptosis is an important cell process and plays a key role in vascular disease and Se-deficient symptoms. In this study, the Se-deficient broiler model was duplicated, miR-33-3p in the vein was overexpressed in response to Se-deficiency, and miR-33-3p target gene E4F transcription factor 1 (E4F1) expression was also confirmed. We utilized ectopic miR-33-3p expression to validate its function for apoptosis. The results showed that miR-33-3p-targeted E4F1 are involved in the glucose-regulated protein 78- (GRP78-) induced endoplasmic reticulum stress (ERS) apoptosis pathway. We presumed that Se deficiency might trigger apoptosis via downregulating miR-33-3p. Interestingly, the miR-33-3p inhibitor and VER-155008 (GRP78 inhibitor) partly hindered the apoptosis caused by Se deficiency. Thus, the above information provides a new avenue toward understanding the mechanism of Se deficiency and reveals a novel apoptotic injury regulation model in vascular disease.
Finding Possible Precursors for the 2015 Cotopaxi Volcano Eruption Using Unsupervised Machine Learning Techniques
Authors: Anzieta Juan C. , Ortiz Hugo D. , Arias Gabriela L. , Ruiz Mario C.
Published: May 2019

Cotopaxi Volcano showed an increased activity since April 2015 and evolved into its eventual mild eruption in August 2015. In this work we use records from a broadband seismic station located at less than 4 km from the vent that encompass data from April to December of 2015, to detect and study low-frequency seismic events. We applied unsupervised learning schemes to group and identify possible premonitory low-frequency seismic families. To find these families we applied a two-stage process in which the events were first separated by their frequency content by applying the k-means algorithm to the spectral density vector of the signals and then were further separated by their waveform by applying Correntropy and Dynamic Time Warping. As a result, we found a particular family related to the volcano’s state of activity by exploring its time distribution and estimating its events’ locations.
Rapidity Dependent Transverse Momentum Spectra of Heavy Quarkonia Produced in Small Collision Systems at the LHC
Authors: Gao Li-Na , Liu Fu-Hu , Li Bao-Chun
Published: May 2019

The rapidity dependent transverse momentum spectra of heavy quarkonia (J/ψ and Υ mesons) produced in small collision systems such as proton-proton (pp) and proton-lead (p-Pb) collisions at center-of-mass energy (per nucleon pair) s (sNN) = 5-13 TeV are described by a two-component statistical model which is based on the Tsallis statistics and inverse power-law. The experimental data measured by the LHCb Collaboration at the Large Hadron Collider (LHC) are well fitted by the model results. The related parameters are obtained and the dependence of parameters on rapidity is analyzed.
Interaction Analysis of Collinear Two Cracks with Unequal Length under Uniaxial Traction
Authors: Yu Bin , Xi Jingyi , Chen Zhonghui , Zhang Lingfan
Published: May 2019

The interaction among different sizes of cracks in materials is one of the key factors leading to the damage of brittle materials. Based on the Kachanov method, the expressions for the stress intensity factors of two collinear cracks with unequal length were obtained and the interaction effect was analyzed. A compression test of a cement mortar specimen containing two cracks and numerical analysis using RFPA2D were performed. The results indicate that the crack interaction can almost be neglected when the crack distance reaches the length of the large crack; the two respective collinear cracks in the specimen grow and do not affect each other when the crack distance reaches the large crack length. The results of compression test and numerical analysis are both in agreement with the theoretical result.
Multiorgan Development of Oxidative and Nitrosative Stress in LPS-Induced Endotoxemia in C57Bl/6 Mice: DHE-BasedIn VivoApproach
Authors: Proniewski Bartosz , Kij Agnieszka , Sitek Barbara , Kelley Eric E. , Chlopicki Stefan
Published: May 2019

Detection of free radicals in tissues is challenging. Most approaches rely on incubating excised sections or homogenates with reagents, typically at supraphysiologic oxygen tensions, to finally detect surrogate, nonspecific end products. In the present work, we explored the potential of using intravenously (i.v.) injected dihydroethidine (DHE) to detect superoxide radical (O2∙-) abundancein vivoby quantification of the superoxide-specific DHE oxidation product, 2-hydroxyethidium (2-OH-E+), as well as ethidium (E+) and DHE in multiple tissues in a murine model of endotoxemia induced by lipopolysaccharide (LPS). LPS was injected intraperitoneally (i.p.), while DHE was delivered via the tail vein one hour before sacrifice. Tissues (kidney, lung, liver, and brain) were harvested and subjected to HPLC/fluorescent analysis of DHE and its monomeric oxidation products. In parallel, electron spin resonance (EPR) spin trapping was used to measure nitric oxide (∙NO) production in the aorta, lung, and liver isolated from the same mice. Endotoxemic inflammation was validated by analysis of plasma biomarkers. The concentration of 2-OH-E+varied in the liver, lung, and kidney; however, the ratios of 2-OH-E+/E+and 2-OH-E+/DHE were increased in the liver and kidney but not in the lung or the brain. An LPS-induced robust level of∙NO burst was observed in the liver, whereas the lung demonstrated a moderate yet progressive increase in the rate of∙NO production. Interestingly, endothelial dysfunction was observed in the aorta, as evidenced by decreased∙NO production 6 hours post-LPS injection that coincided with the inflammatory burden of endotoxemia (e.g. elevated serum amyloid A and prostaglandin E2). Combined, these data demonstrate that systemic delivery of DHE affords the capacity to specifically detect O2∙-productionin vivo. Furthermore, the ratio of 2-OH-E+/E+oxidation products in tissues provides a tool for comparative insight into the oxidative environments in various organs. Based on our findings, we demonstrate that the endotoxemic liver is susceptible to both O2∙--mediated and nonspecific oxidant stress as well as nitrosative stress. Oxidant stress in the lung was detected to a lesser extent, thus underscoring a differential response of liver and lung to endotoxemic injury induced by intraperitoneal LPS injection.
Study of Numerical Simulation during ECAP Processing of Can Based on Smooth Particle Hydrodynamics
Authors: Niu Xiaofeng , Wang Chenchen , Chan K. C. , Wang Han , Feng Shidong
Published: May 2019

ECAP (Equal Channel Angular Pressing) is a well‐known technique by which a specimen is pressed into an ECAP die to improve the mechanical properties by the nearly pure shear during the deformation process. In the ECAP processing of can, the specimen is canned with a protection material layer to avoid the cracking during deformation. At present, most simulation studies of ECAP are conducted based on the finite element method, in which large deformation can cause serious mesh distortion, resulting in a decrease of the simulation accuracy. In this study, based on SPH (Smooth Particle Hydrodynamics), we utilize the invalid particles and crack treatment techniques, building an ECAP mathematical model incorporating damage prediction, in order to simulate crack initiation and dynamic extension in the ECAP process. In simulation of pure magnesium during ECAP at room temperature using industrial pure iron as the canned material, the simulation results based on SPH method show that the plastic deformation of the pure magnesium specimen is homogeneous in both the vertical direction and the extrusion direction. The average equivalent strain value of the specimen in the major deformation area is 1.31, which is similar to the finite element simulation result in which the average equivalent strain value of the major deformation area is 1.24. From the damage perspective, the maximum damage values of the inside specimen obtained by the SPH method and the finite element method are both less than 0.16, with both values being far lower than the critical fracture accumulated damage value. The test results well match the simulation results.
Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal K+-Cl-Cotransporter KCC2
Authors: Tillman Luke , Zhang Jinwei
Published: May 2019

Chloride (Cl-) homeostasis is an essential process involved in neuronal signalling and cell survival. Inadequate regulation of intracellular Cl-interferes with synaptic signalling and is implicated in several neurological diseases. The main inhibitory neurotransmitter of the central nervous system isγ-aminobutyric acid (GABA). GABA hyperpolarises the membrane potential by activating Cl-permeableGABAAreceptor channels(GABAAR). This process is reliant on Cl-extruder K+-Cl-cotransporter 2 (KCC2), which generates the neuron’s inward, hyperpolarising Cl-gradient. KCC2 is encoded by the fifth member of the solute carrier 12 family (SLC12A5)and has remained a poorly understood component in the development and severity of many neurological diseases for many years. Recent advancements in next-generation sequencing and specific gene targeting, however, have indicated that loss of KCC2 activity is involved in a number of diseases including epilepsy and schizophrenia. It has also been implicated in neuropathic pain following spinal cord injury. Any variant ofSLC12A5that negatively regulates the transporter’s expression may, therefore, be implicated in neurological disease. A recent whole exome study has discovered several causative mutations in patients with epilepsy. Here, we discuss the implications of KCC2 in neurological disease and consider the evolving evidence for KCC2’s potential as a therapeutic target.
Flame-Retardant and Smoke Suppression Properties of Nano MgAl-LDH Coating on Bamboo Prepared by an In Situ Reaction
Authors: Yao Xiaoling , Du Chungui , Hua Yating , Zhang Jingjing , Peng Rui , Huang Qiuli , Liu Hongzhi
Published: May 2019

In recent years, bamboo has been widely used for building materials and household goods. However, bamboo is flammable, so a flame-retardant treatment for bamboo is urgently needed. In this work, nano MgAl-layered double hydroxide (MgAl-LDH) coated on bamboo, which was called MgAl-LB, was synthesized by an in situ one-step method. To determine the optimal in situ time, the effects of different reaction times on LDH growth on the bamboo surface and the flame retardancy of the MgAl-LBs were investigated. The SEM observations show that LDH growth on the surface of bamboo was basically saturated when the in situ reaction time was 24 h. Abrasion experiments show that MgAl-LDH coating has good abrasion resistance. The fire performance of the MgAl-LBs was evaluated by cone calorimeter tests, which indicated that the THR and TSP of the MgAl-LBs were significantly lower than those of untreated bamboo. Taking into account the energy consumption problem, determining the reaction time of 24 h is the optimal reaction time. Compared with untreated bamboo, the THR and TSP of MgAl-LB prepared at 24 h decreased by 33.3% and 88.9%, respectively.
Mitochondrial Entry of Cytotoxic Proteases: A New Insight into the Granzyme B Cell Death Pathway
Authors: Martinvalet Denis
Published: May 2019

The mitochondria represent an integration and amplification hub for various death pathways including that mediated by granzyme B (GB), a granule enzyme expressed by cytotoxic lymphocytes. GB activates the proapoptotic B cell CLL/lymphoma 2 (Bcl-2) family member BH3-interacting domain death agonist (BID) to switch on the intrinsic mitochondrial death pathway, leading to Bcl-2-associated X protein (Bax)/Bcl-2 homologous antagonist/killer- (Bak-) dependent mitochondrial outer membrane permeabilization (MOMP), the dissipation of mitochondrial transmembrane potential (ΔΨm), and the production of reactive oxygen species (ROS). GB can also induce mitochondrial damage in the absence of BID, Bax, and Bak, critical for MOMP, indicating that GB targets the mitochondria in other ways. Interestingly, granzyme A (GA), GB, and caspase 3 can all directly target the mitochondrial respiratory chain complex I for ROS-dependent cell death. Studies of ROS biogenesis have revealed that GB must enter the mitochondria for ROS production, making the mitochondrial entry of cytotoxic proteases (MECP) an unexpected critical step in the granzyme death pathway. MECP requires an intact ΔΨm and is mediated though Sam50 and Tim22 channels in a mtHSP70-dependent manner. Preventing MECP severely compromises GB cytotoxicity. In this review, we provide a brief overview of the canonical mitochondrial death pathway in order to put into perspective this new insight into the GB action on the mitochondria to trigger ROS-dependent cell death.
Mitochondrial Transfer of Wharton’s Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts
Authors: Lin Tsu-Kung , Chen Shang-Der , Chuang Yao-Chung , Lan Min-Yu , Chuang Jiin-Haur , Wang Pei-Wen , Hsu Te-Yao , Wang Feng-Sheng , Tsai Meng-Han , Huang Sheng-Teng , Wang Xiao-Wen , Tsai Po-Chin , Lin Hung-Yu , Liou Chia-Wei
Published: May 2019

Wharton’s jelly mesenchymal stem cells (WJMSCs) transfer healthy mitochondria to cells harboring a mitochondrial DNA (mtDNA) defect. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major subgroups of mitochondrial diseases, caused by the mt.3243A>G point mutation in the mitochondrial tRNALeu(UUR) gene. The specific aim of the study is to investigate whether WJMSCs exert therapeutic effect for mitochondrial dysfunction in cells of MELAS patient through donating healthy mitochondria. We herein demonstrate that WJMSCs transfer healthy mitochondria into rotenone-stressed fibroblasts of a MELAS patient, thereby eliminating mutation burden and rescuing mitochondrial functions. In the coculture system in vitro study, WJMSCs transferred healthy mitochondria to rotenone-stressed MELAS fibroblasts. By inhibiting actin polymerization to block tunneling nanotubes (TNTs), the WJMSC-conducted mitochondrial transfer was abrogated. After mitochondrial transfer, the mt.3243A>G mutation burden of MELAS fibroblasts was reduced to an undetectable level, with long-term retention. Sequencing results confirmed that the transferred mitochondria were donated from WJMSCs. Furthermore, mitochondrial transfer of WJMSCs to MELAS fibroblasts improves mitochondrial functions and cellular performance, including protein translation of respiratory complexes, ROS overexpression, mitochondrial membrane potential, mitochondrial morphology and bioenergetics, cell proliferation, mitochondrion-dependent viability, and apoptotic resistance. This study demonstrates that WJMSCs exert bioenergetic therapeutic effects through mitochondrial transfer. This finding paves the way for the development of innovative treatments for MELAS and other mitochondrial diseases.
How Well Does Diadochokinetic Task Performance Predict Articulatory Imprecision? Differentiating Individuals with Parkinson’s Disease from Control Subjects
Authors: Karlsson Fredrik , Hartelius Lena
Published: May 2019

Objective: To investigate whether syllables produced in an oral diadochokinetic (DDK) task may be quantified so that persons with Parkinson’s disease (PD) perceived to have reduced articulatory precision when reading may be correctly identified using that quantification. Patients and Methods: Syllable sequences from 38 speakers with PD and 38 gender- and age-matched control speakers (normal controls [NC]) were quantified acoustically and evaluated in terms of (1) the speakers’ ability to accurately predict speaker group membership (PD or NC) and (2) their ability to predict reduced/non-reduced articulatory precision. Results: A balanced accuracy of 80–93% in predicting speaker group membership was achieved. The best measures were related to the proportion of a syllable made up of a vowel, amplitude slope and syllable-to-syllable variation in duration and amplitude. The best material was that based on /ka/. Reduced articulatory precision was accurately predicted from DDK measures in 89% of the samples. Release-transient prominence and voicing during the onset of plosives were particularly strong predictors. Conclusions: DDK sequences can predict articulatory imprecision as observed in another speech task. The linking of performance across speech tasks probably requires measures of stability in syllable durations and amplitudes, as well as measures of subsyllabic acoustic features.
Semifluorinated Alkane Eye Drops in Chronic Ocular Graft-versus-Host Disease: A Prospective, Multicenter, Noninterventional Study
Authors: Eberwein Philipp , Krösser Sonja , Steven Philipp
Published: May 2019

Purpose: Ocular graft-versus-host disease (oGvHD) following allogeneic hematopoietic stem cell transplantation develops as severe dry eye disease (DED) and is initially treated with lubricants, although no clinical trials are available using artificial tears in oGvHD. This trial was set up to test perfluorohexyloctane (NovaTears®) as nonpreserved layer-forming agent for the treatment of DED in oGvHD. Methods: 25 patients with severe DED due to oGvHD received 1 drop perfluorohexyloctane 4 times daily during a prospective, multicenter, observational 12-week study on top of established topical therapy. Clinical parameters included Schirmer test, tear film breakup time, corneal staining, meibum secretion and ocular surface disease index. Adverse events, visual acuity and intraocular pressure were key safety parameters. Results: From 25 patients recruited, 23 presented for the second visit. Perfluorohexyloctane treatment did not lead to any changes in clinical or safety parameters but led to fast relief in symptoms in 57% of the patients. One adverse reaction occurred. Conclusions: This study showed no change in clinical signs in severe DED due to oGvHD, which was not unexpected due to the underlying pathomechanisms. However, the study showed improvement of symptoms in individual patients allowing application of perfluorohexyloctane as an additional symptomatic therapy in oGvHD.
Podocyte Injury in Autosomal Dominant Polycystic Kidney Disease
Authors: Cebeci Egemen , Ekinci Iskender , Gursu Meltem , Coskun Cihan , Karadag Serhat , Uzun Sami , Behlul Ahmet , Senel Tuba Elif , Kazancioglu Rumeyza , Ozturk Savas
Published: May 2019

Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is a tubulointerstitial disease. Different degrees of glomerular affection in ADPKD may affect the further course of disease in which it may hypothetically be secondary to the result of glomerular involvement causing podocyte injury. Our aim was to compare urinary excretion of podocin and podocalyxin, which are biomarkers of podocyte injury, and to assess their relationship with proteinuria and renal function in ADPKD. Methods: Fifty-six patients with ADPKD and 28 volunteers were enrolled to study. Podocin, podocalyxin protein levels, and proteinuria were measured in urine. Patients were categorized based on their estimated glomerular filtration rate (eGFR). Results: Patients with ADPKD had higher podocin and podocalyxin levels compared to the control group. The levels of podocin and podocalyxin were higher in ADPKD patients both with eGFR ≥60 mL/min/1.73 m2 and with eGFR <60 mL/min/1.73 m2 than in controls. The levels of podocin and podocalyxin were higher in ADPKD patients with eGFR <60 mL/min/1.73 m2 than in ADPKD patients with eGFR ≥60 mL/min/1.73 m2. Podocin and podocalyxin were negatively correlated with eGFR and positively correlated with urine protein to creatinine ratio in ADPKD patients. Conclusion: Urine biomarkers of podocytes injury were significantly higher in ADPKD patients even in the early stage of the disease than in the control group. It should be clarified whether these biomarkers can provide new prognostic parameters for disease surveillance.
Symptomatic Uncomplicated Diverticular Disease and Incidence of Unexpected Abscess during Sigmoidectomy: A Multicenter Prospective Observational Study
Authors: Mari Giulio M. , Crippa Jacopo , Borroni Giacomo , Cocozza Eugenio , Roscio Francesco , Scandroglio Ildo , Origi Matteo , Ferrari Giovanni , Forgione Antonello , Riggio Valentina , Pugliese Raffaele , Costanzi Andrea T.M. , Maggioni Dario ,   on behalf of the AIMS Academy Clinical Research Network
Published: May 2019

Background: Symptomatic uncomplicated diverticular disease can affect patients’ everyday routine. Considerable efforts have been made to identify clinical features that correlate to the severity of the disease. Unexpected intraoperative abscesses are reported in large retrospective series, showing how uncomplicated symptoms and presentations can underlie a complicated disease. The aim of this study was to investigate the incidence of pericolic or intramural abscess in patients undergoing elective sigmoidectomy for symptomatic uncomplicated diverticular disease and see if chronic symptoms correlate to the presence of an abscess. Methods: Between January 2016 and June 2018, we prospectively collected data of patients who were given indication to elective sigmoidectomy for symptomatic uncomplicated diverticular disease. Patients were divided into 3 groups: acute resolving, smoldering, and atypical according to a previously described classification of uncomplicated diverticular disease. Results: One hundred fifty-eight consecutive patients were enrolled in the study. The median age was 63 years (22– 88), and the mean body mass index was 26 (±7) kg/m2. There were 114 patients in the acute resolving group, 36 in the smoldering group, and 8 in the atypical group. An unexpected abscess was reported in 75 patients (47.5%) during surgery or pathological examination. The incidence of ­abscess was greater for patient in the smoldering group (p = 0.0243). Conclusion: Our series of patients affected by symptomatic uncomplicated diverticular disease showed an incidence of unexpected pericolic or intramural abscess of 47.5%. Patients affected by smoldering diverticular disease presented a greater abscess rate.
Clinical Manifestations, Immunological Characteristics and Genetic Analysis of Patients with Hyper-Immunoglobulin M Syndrome in Iran
Authors: Tafakori Delbari Mitra , Cheraghi Taher , Yazdani Reza , Fekrvand Saba , Delavari Samaneh , Azizi Gholamreza , Chavoshzadeh Zahra , Mahdaviani Seyed Alireza , Ahanchian Hamid , Khoshkhui Maryam , Behmanesh Fatemeh , Aleyasin Soheila , Esmaeilzadeh Hossein , Jabbari-Azad  Farahzad  , Fallahpour Morteza , Zamani Mohammadali , Madani Seyedeh Panid , Moazzami Bobak , Habibi Sima , Rezaei Arezou , Lotfalikhani Azadeh , Movahed Masoud , Shariat Mansoureh , Kalantari Arash , Babaei Delara , Darabi Mahshid , Parvaneh Nima , Rezaei Nima , Abolhassani Hassan , Aghamohammadi Asghar
Published: May 2019

Background: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM. Methods: Clinical and immunological data were collected from the 75 patients’ medical records diagnosed in Children’s Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing. Results: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients. Conclusion: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.
Pterostilbene Ameliorates Nephropathy Injury in Streptozotocin-Induced Diabetic Rats
Authors: Zhang Ying , Ren Shaoyu , Ji Ying , Liang Yafeng
Published: May 2019

Background: Our study investigated the therapeutic role and potential mechanisms of pterostilbene (PS) in diabetic nephropathy (DN) rats. Methods: DN models were established by high-fat diet after streptozotocin injection. A total of 50 Sprague-Dawley rats were randomly divided into control, DN, PS-treated groups (PS-H, PS-M, PS-L). PS was administered to rats by gavage for 8 weeks at 3 different doses (25, 10, and 5 mg/kg/day). The levels of oxidative stress activity (superoxide dismutase [SOD], malondialdehyde [MDA], glutathione peroxidase [GSH-PX]) and inflammatory factors (tumor necrosis factor [TNF]-α, interleukin (IL)-6, IL-1β, monocyte chemoattractant factor [MCP]-1) were detected by ­ELISA. TGF-β, Smad1, and fibronectin (FN) were measured through immunohistochemistry. The relative expressions of phospho-IκBα/IκBα, phospho-IκB kinases (IKK)β/IKKβ, phospho-nuclear factor-κB (NF-κB) p65/NF-κB p65 were detected by western blot. Results: Compared with DN group, the levels of TNF-α, IL-6, IL-1β, and MCP-1 were decreased in the PS-H group (p < 0.05). Meanwhile, the levels of SOD, MDA, GSH-PX improved in kidney and serum in PS-H groups (p< 0.05). PS also significantly decreased the level of phospho-NF-κB p65 and increased the levels of phospho- IKKβ and phospho-Iκ-Bα (p < 0.05). The results showed that PS treatment decreased TGF-β, Smad1, and FN expressions. Conclusion: PS had potential therapeutic effects on DN, which may be related to the regulation of NF-κB pathway.