bluuebunny/crossref_metadata_2025 huggingface dataset:
Mori Ramulus Inhibits Pancreatic β-Cell Apoptosis and Prevents Insulin Resistance by Restoring Hepatic Mitochondrial Function
Authors: Han Taewon , Ko Eun , Kim Minji , Choi Moonsung , Lee Changho , Kim In-Ho , Shin Sooim , Um Min Young
Published: June 2021

Type 2 diabetes mellitus is characterized by insulin resistance and pancreatic beta (β)-cell dysfunction. Accumulating evidence suggests that mitochondrial dysfunction may cause insulin resistance in peripheral tissues. As commercial hypoglycemic drugs have side effects, it is necessary to develop safe and effective natural compound-based hypoglycemic treatments. This study aimed to investigate the hypoglycemic effects of Mori Ramulus ethanol extract (ME) in a high-fat diet (HFD)-induced diabetes mouse model to decipher the underlying mechanisms focusing on apoptosis and mitochondrial function. ME significantly decreased tunicamycin-induced apoptotic cell death and increased insulin secretion following glucose stimulation in NIT-1 pancreatic β-cells. Tunicamycin-exposed NIT-1 pancreatic β-cells showed elevated reactive oxygen species levels and reduced mitochondrial membrane potential, which were reversed by ME treatment. ME inhibited the tunicamycin-induced apoptosis cascade in tunicamycin-exposed NIT-1 pancreatic β-cells. In HFD diabetic mice, the serum-free fatty acid and insulin levels decreased following a 15-week ME administration. Glucose and insulin tolerance tests showed that ME improved insulin sensitivity. Moreover, ME ameliorated pancreatic β-cell mass loss in diabetic mice. Finally, ME-treated HFD-fed mice showed improved hepatic mitochondrial function resulting in insulin sensitivity in target tissues. Thus, ME provides protection against pancreatic β-cell apoptosis and prevents insulin resistance by improving mitochondrial function.
Protective Effects of Oroxylin A on Retinal Ganglion Cells in Experimental Model of Anterior Ischemic Optic Neuropathy
Authors: Chien Jia-Ying , Lin Shu-Fang , Chou Yu-Yau , Huang Chi-Ying F. , Huang Shun-Ping
Published: June 2021

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute vision loss in older people, and there is no effective therapy. The effect of the systemic or local application of steroids for NAION patients remains controversial. Oroxylin A (OA) (5,7-dihydroxy-6-methoxyflavone) is a bioactive flavonoid extracted from Scutellariae baicalensis Georgi. with various beneficial effects, including anti-inflammatory and neuroprotective effects. A previous study showed that OA promotes retinal ganglion cell (RGC) survival after optic nerve (ON) crush injury. The purpose of this research was to further explore the potential actions of OA in ischemic injury in an experimental anterior ischemic optic neuropathy (rAION) rat model induced by photothrombosis. Our results show that OA efficiently attenuated ischemic injury in rats by reducing optic disc edema, the apoptotic death of retinal ganglion cells, and the infiltration of inflammatory cells. Moreover, OA significantly ameliorated the pathologic changes of demyelination, modulated microglial polarization, and preserved visual function after rAION induction. OA activated nuclear factor E2 related factor (Nrf2) signaling and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1 (HO-1) in the retina. We demonstrated that OA activates Nrf2 signaling, protecting retinal ganglion cells from ischemic injury, in the rAION model and could potentially be used as a therapeutic approach in ischemic optic neuropathy.
Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells
Authors: Barvitenko Nadezhda , Skverchinskaya Elisaveta , Lawen Alfons , Matteucci Elena , Saldanha Carlota , Uras Giuseppe , Manca Alessia , Aslam Muhammad , Pantaleo Antonella
Published: June 2021

Endothelial cells (ECs) are exposed to molecular dioxygen and its derivative reactive oxygen species (ROS). ROS are now well established as important signaling messengers. Excessive production of ROS, however, results in oxidative stress, a significant contributor to the development of numerous diseases. Here, we analyze the experimental data and theoretical concepts concerning positive pro-survival effects of ROS on signaling pathways in endothelial cells (ECs). Our analysis of the available experimental data suggests possible positive roles of ROS in induction of pro-survival pathways, downstream of the Gi-protein-coupled receptors, which mimics insulin signaling and prevention or improvement of the endothelial dysfunction. It is, however, doubtful, whether ROS can contribute to the stabilization of the endothelial barrier.
Coenzyme Q10 and Cardiovascular Diseases
Authors: Gutierrez-Mariscal Francisco M. , de la Cruz-Ares Silvia , Torres-Peña Jose D. , Alcalá-Diaz Juan F. , Yubero-Serrano Elena M. , López-Miranda José
Published: June 2021

Coenzyme Q10 (CoQ10), which plays a key role in the electron transport chain by providing an adequate, efficient supply of energy, has another relevant function as an antioxidant, acting in mitochondria, other cell compartments, and plasma lipoproteins. CoQ10 deficiency is present in chronic and age-related diseases. In particular, in cardiovascular diseases (CVDs), there is a reduced bioavailability of CoQ10 since statins, one of the most common lipid-lowering drugs, inhibit the common pathway shared by CoQ10 endogenous biosynthesis and cholesterol biosynthesis. Different clinical trials have analyzed the effect of CoQ10 supplementation as a treatment to ameliorate these deficiencies in the context of CVDs. In this review, we focus on recent advances in CoQ10 supplementation and the clinical implications in the reduction of cardiovascular risk factors (such as lipid and lipoprotein levels, blood pressure, or endothelial function) as well as in a therapeutic approach for the reduction of the clinical complications of CVD.
DHA and Its Elaborated Modulation of Antioxidant Defenses of the Brain: Implications in Aging and AD Neurodegeneration
Authors: Díaz Mario , Mesa-Herrera Fátima , Marín Raquel
Published: June 2021

DHA (docosahexaenoic acid) is perhaps the most pleiotropic molecule in nerve cell biology. This long-chain highly unsaturated fatty acid has evolved to accomplish essential functions ranging from structural components allowing fast events in nerve cell membrane physiology to regulation of neurogenesis and synaptic function. Strikingly, the plethora of DHA effects has to take place within the hostile pro-oxidant environment of the brain parenchyma, which might suggest a molecular suicide. In order to circumvent this paradox, different molecular strategies have evolved during the evolution of brain cells to preserve DHA and to minimize the deleterious effects of its oxidation. In this context, DHA has emerged as a member of the “indirect antioxidants” family, the redox effects of which are not due to direct redox interactions with reactive species, but to modulation of gene expression within thioredoxin and glutathione antioxidant systems and related pathways. Weakening or deregulation of these self-protecting defenses orchestrated by DHA is associated with normal aging but also, more worryingly, with the development of neurodegenerative diseases. In the present review, we elaborate on the essential functions of DHA in the brain, including its role as indirect antioxidant, the selenium connection for proper antioxidant function and their changes during normal aging and in Alzheimer’s disease.
Effects of Vitamin E and Coenzyme Q10 Supplementation on Oxidative Stress Parameters in Untrained Leisure Horses Subjected to Acute Moderate Exercise
Authors: Nemec Svete Alenka , Vovk Tomaž , Bohar Topolovec Mojca , Kruljc Peter
Published: June 2021

The effects of antioxidant supplements on exercise-induced oxidative stress have not been investigated in untrained leisure horses. We investigated the effects of 14-day supplementation with vitamin E (1.8 IU/kg/day), coenzyme Q10 (CoQ10; ubiquinone; 800 mg/day), and a combination of both (the same doses as in mono-supplementation) on the blood levels of CoQ10, vitamin E, and oxidative stress parameters in untrained leisure horses subjected to acute moderate exercise. Correlations between lipid peroxidation and muscle enzyme leakage were also determined. Forty client-owned horses were included in the study, with 10 horses in each of the antioxidant and placebo (paraffin oil) groups. Blood parameters were measured before supplementation, before and immediately after exercise, and after 24 h of rest. The differences in individual parameters between blood collection times and groups were analysed with linear mixed models (p ˂ 0.05). None of the supplemented antioxidants affected vitamin E and CoQ10 concentrations, oxidative stress parameters, or serum muscle enzymes. Lipid peroxidation occurred in horses supplemented with placebo and CoQ10 but not in horses supplemented with vitamin E or the combination of both antioxidants. These results suggest that vitamin E alone or in combination with CoQ10 prevented lipid peroxidation in untrained leisure horses subjected to acute moderate exercise.
Software Project Management Using Machine Learning Technique—A Review
Authors: Mahdi Mohammed Najah , Mohamed Zabil Mohd Hazli , Ahmad Abdul Rahim , Ismail Roslan , Yusoff Yunus , Cheng Lim Kok , Azmi Muhammad Sufyian Bin Mohd , Natiq Hayder , Happala Naidu Hushalini
Published: June 2021

Project management planning and assessment are of great significance in project performance activities. Without a realistic and logical plan, it isn’t easy to handle project management efficiently. This paper presents a wide-ranging comprehensive review of papers on the application of Machine Learning in software project management. Besides, this paper presents an extensive literature analysis of (1) machine learning, (2) software project management, and (3) techniques from three main libraries, Web Science, Science Directs, and IEEE Explore. One-hundred and eleven papers are divided into four categories in these three repositories. The first category contains research and survey papers on software project management. The second category includes papers that are based on machine-learning methods and strategies utilized on projects; the third category encompasses studies on the phases and tests that are the parameters used in machine-learning management and the final classes of the results from the study, contribution of studies in the production, and the promotion of machine-learning project prediction. Our contribution also offers a more comprehensive perspective and a context that would be important for potential work in project risk management. In conclusion, we have shown that project risk assessment by machine learning is more successful in minimizing the loss of the project, thereby increasing the likelihood of the project success, providing an alternative way to efficiently reduce the project failure probabilities, and increasing the output ratio for growth, and it also facilitates analysis on software fault prediction based on accuracy.
Thermal Stability Design of Asymmetric Support Structure for an Off-Axis Space Camera
Authors: Song Weiyang , Xie Peng , Liu Shuai , Xie Yunqiang
Published: June 2021

With the development of space optical remote sensing technology, especially off-axis space cameras, the thermal dimensional stability of the support structure has become increasingly demanding. However, the asymmetry of the camera structure has not been fully considered in the past design of the thermal stability of off-axis cameras. In order to solve this problem, a support structure with very low thermal deformation in the asymmetric direction is presented in this paper for an off-axis TMA camera. By means of the negative axial thermal expansion coefficient of carbon-fiber-reinforced plastics (CFRP), a composite laminate with near zero-expansion was obtained by adjusting the direction of fiber laying, and the asymmetric feature of the off-axis remote sensing camera structure was fully considered, thus enabling the support structure to have good thermal dimensional stability. We carried out a thermal load analysis and an optical analysis of the whole camera in the case of a temperature rise of 5 °C. The results show that the zero-expansion support structure has good thermal stability, and the thermal deformation in the asymmetric direction of the camera is obviously smaller than that of the isotropic laminate support structure. Compared with the isotropic support structure, the influence of thermal deformation on MTF is reduced from 10.43% to 2.61%. This study innovatively incorporates the asymmetry of the structure into the thermal sta-bility design of an off-axis TMA camera and provides a reference for the thermal stability design of other off-axis space cameras.
Towards a Fast, Open-Path Laser Hygrometer for Airborne Eddy Covariance Measurements
Authors: Witt Felix , Nwaboh Javis , Bohlius Henning , Lampert Astrid , Ebert Volker
Published: June 2021

Water vapor fluxes play a key role in the energy budget of the atmosphere, and better flux measurements are needed to improve our understanding of the formation of clouds and storms. Large-scale measurements of these fluxes are possible by employing the eddy correlation (EC) method from an aircraft. A hygrometer used for such measurements needs to deliver a temporal resolution of at least 10 Hz while reliably operating in the harsh conditions on the exterior of an aircraft. Here, we present a design concept for a calibration-free, first-principles, open-path dTDLAS hygrometer with a planar, circular and rotationally symmetric multipass cell with new, angled coupling optics. From our measurements, the uncertainty of the instrument is estimated to be below 4.5% (coverage factor k = 1). A static intercomparison between a dTDLAS prototype of the new optics setup and a traceable dew point mirror hygrometer was conducted and showed a systematic relative deviation of 2.6% with a maximal relative error of 2.2%. Combined with a precision of around 1 ppm H2O at tropospheric conditions, the newly designed setup fulfills the static precision and accuracy requirements of the proposed airborne EC hygrometer.
Measurements of N2, CO2, Ar, O2 and Air Pressure Broadening Coefficients of the HCl P(5) Line in the 1–0 Band Using an Interband Cascade Laser
Authors: Qu Zhechao , Nwaboh Javis A. , Li Gang , Werhahn Olav , Ebert Volker
Published: June 2021

We determine the CO2, N2, Ar, O2 and air pressure broadening coefficients of the H35Cl P(5) absorption line at 2775.77 cm−1 in the fundamental (1←0) band using a newly developed direct tunable diode laser absorption spectroscopy (dTDLAS)-based spectrometer employing a mid-IR interband cascade laser (ICL). For the first time, a reliable and consistent set of five different foreign pressure broadening coefficients for the same HCl P(5) line has been measured by a consistent metrological approach covering pressures from 100 to 600 hPa at temperatures of 294 and 295 K. The relative uncertainties of the stated CO2, N2, Ar, O2 and Air pressure broadening coefficients are in 1–3% range. The results are compared to previously available literature data—two broadening coefficients have been improved in accuracy and two have been determined for the first time in the sub 1000 hPa pressure range.
Binary-Like Topology Optimization of Piezoelectric Metamaterial Plate with Interface Circuits Using Extended Plane Wave Expansion Method
Authors: Chen Zhongsheng , Xiong Yeping , Wei Yongxiang
Published: June 2021

Piezoelectric metamaterial plate (PMP) is being investigated for structural vibration energy harvesting (SVEH), in which an interface circuit is often used. Thus, it is a challenge to perform bandgap optimization of such an elastic–electro–mechanical coupling system. This paper presents a binary-like topology optimization scheme by dividing the unit cell into identical pieces, where a {0, 1} matrix is optimized to indicate material distribution. Firstly, a unified motion equation is derived for the elastic plate and the piezoelectric patch, and an electromechanical coupling model is built for a self-powered synchronized charge extraction circuit. Then, an extended plane wave expansion method is presented to model the bandgap character of the PMP with interface circuits (PMPICs), and the numerical solution of the dispersion curves is derived based on the Bloch theorem. Next, an extended genetic algorithm is applied for the topology optimization of the PMPIC. In the end, numerical and finite element simulations are performed to validate the proposed method. The results demonstrate that both the structure and the circuit can be optimized simultaneously to obtain the maximum first-order bandgap at a given central frequency. Therefore, the proposed method should provide an effective solution for the topology optimization of a PMPIC for broadband SVEH.
Review of Hygroscopic Coating on Aluminum Fin Surface of Air Conditioning Heat Exchanger
Authors: He Song , Chen Wang , Yang Wansheng , Zhao Xudong
Published: June 2021

Air conditioning energy consumption accounts for most building energy consumption, indoor dehumidification is the main cause of air conditioning energy consumption. Optimize the dehumidification methods of air conditioning systems have great significance to the development of green buildings and people’s pursuit of comfort. Improvement of fins on air conditioning heat exchangers is a hot topic of current research and has achieved considerable results in terms of indoor dehumidification and energy saving compared to traditional air conditioners. This paper reviews two kinds of heat exchangers modified by coating, including desiccant-coated heat exchangers and hydrophobic/hydrophilic coated heat exchangers. For desiccant-coated heat exchangers, the preparation methods of advanced desiccant materials and the possibilities of using this material to achieve excellent energy efficiencies were presented, and the operating parameters that affect thermal performance and dehumidification are determined, including airflow temperature, air velocity, inlet air relative humidity, and regeneration temperature. For hydrophobic/hydrophilic coated heat exchangers, different kinds of hybrid hydrophobic-hydrophilic surfaces are highlighted for they are a high water droplet nucleation rate and surface heat transfer efficiency. In addition, the challenges and future works are explained at last. This paper will provide a valuable reference for the follow-up research, which will be helpful for indoor humidity control and reducing the energy consumption of air conditioning.
Knee Osteoarthritis Classification Using 3D CNN and MRI
Authors: Guida Carmine , Zhang Ming , Shan Juan
Published: June 2021

Osteoarthritis (OA) is the most common form of arthritis and can often occur in the knee. While convolutional neural networks (CNNs) have been widely used to study medical images, the application of a 3-dimensional (3D) CNN in knee OA diagnosis is limited. This study utilizes a 3D CNN model to analyze sequences of knee magnetic resonance (MR) images to perform knee OA classification. An advantage of using 3D CNNs is the ability to analyze the whole sequence of 3D MR images as a single unit as opposed to a traditional 2D CNN, which examines one image at a time. Therefore, 3D features could be extracted from adjacent slices, which may not be detectable from a single 2D image. The input data for each knee were a sequence of double-echo steady-state (DESS) MR images, and each knee was labeled by the Kellgren and Lawrence (KL) grade of severity at levels 0–4. In addition to the 5-category KL grade classification, we further examined a 2-category classification that distinguishes non-OA (KL ≤ 1) from OA (KL ≥ 2) knees. Clinically, diagnosing a patient with knee OA is the ultimate goal of assigning a KL grade. On a dataset with 1100 knees, the 3D CNN model that classifies knees with and without OA achieved an accuracy of 86.5% on the validation set and 83.0% on the testing set. We further conducted a comparative study between MRI and X-ray. Compared with a CNN model using X-ray images trained from the same group of patients, the proposed 3D model with MR images achieved higher accuracy in both the 5-category classification (54.0% vs. 50.0%) and the 2-category classification (83.0% vs. 77.0%). The result indicates that MRI, with the application of a 3D CNN model, has greater potential to improve diagnosis accuracy for knee OA clinically than the currently used X-ray methods.
Mini-Review: Recent Technologies of Electrode and System in the Enzymatic Biofuel Cell (EBFC)
Authors: A. Karim Nabila , Yang Hsiharng
Published: June 2021

Enzymatic biofuel cells (EBFCs) is one of the branches of fuel cells that can provide high potential for various applications. However, EBFC has challenges in improving the performance power output. Exploring electrode materials is one way to increase enzyme utilization and lead to a high conversion rate so that efficient enzyme loading on the electrode surface can function correctly. This paper briefly presents recent technologies developed to improve bio-catalytic properties, biocompatibility, biodegradability, implantability, and mechanical flexibility in EBFCs. Among the combinations of materials that can be studied and are interesting because of their properties, there are various nanoparticles, carbon-based materials, and conductive polymers; all three have the advantages of chemical stability and enhanced electron transfer. The methods to immobilize enzymes, and support and substrate issues are also covered in this paper. In addition, the EBFC system is also explored and developed as suitable for applications such as self-pumping and microfluidic EBFC.
kf Evaluation in GFRP Composites by Thermography
Authors: De Giorgi Marta , Nobile Riccardo , Palano Fania
Published: June 2021

Since the presence of a notch in a mechanical component causes a reduction in the fatigue strength, it is important to know the kf value for a given notch geometry and material. This parameter is fundamental in the fatigue design of aeronautical components that are mainly made of composites. kf is available in the literature for numerous types of notch but only for traditional materials such as metals. This paper presents a new practice, based on thermographic data, for the determination of the fatigue notch coefficient kf in composite notched specimens. The innovative aspect of this study is therefore to propose the application on composite materials of a new thermographic procedure to determine kf for several notch geometries: circular, U and V soft and severe notches. It was calculated, for each type of notch, as the ratio between the fatigue limits obtained on the cold and hot zone corresponding to the smooth and notched specimen, respectively. Consequently, this research activity provides, for the first time, a little database of kf for two particular typologies of composite materials showing a fast way to collect further values for different laminates and notch geometries.
Case Study—An Extreme Example of Soil–Structure Interaction and the Damage Caused by Works on Foundation Strengthening
Authors: Santrač Petar , Grković Slobodan , Kukaras Danijel , Đuric Neđo , Svilar Mila
Published: June 2021

This paper describes the works on foundation strengthening of the towers of the Cathedral of St. Theresa of Avila in Subotica and the damages caused by these works. Strengthening was performed by means of jacked-in piles and deep soil injection. The construction of the Cathedral began in 1773 and it lasted for several decades with frequent interruptions and changes to the project. The present appearance of the facade was created in 1912. According to historic data, several years after construction, the cracks appeared on the front facade. With time, these cracks became more pronounced, and in 2015, when the remediation project started, the total width of major cracks reached about 15 cm. The first contemporary attempt to repair the towers was made in 2017 by inserting piles beneath the foundations. These works were interrupted due to increased settlements and the appearance of new cracks. In the second attempt, the strengthening was performed by deep injection of soil with expansive resins. During these works, settlements and damages intensified even more, causing the works to be halted in 2018. Analysis of the whole structure and revaluation of all the results, obtained from continuous monitoring of settlements and crack widths from the previous period, led to the new remediation proposal. The imperative was to retain the original appearance of the Cathedral facades while performing the total reconstruction of the upper sections of the front facade. This implies that the overall weight of the reconstructed parts is to be decreased, while the strength is to be increased. Strong structural connections are planned, both among the two towers, and between the towers and the nave. These clear structural solutions will lead to reduced stresses within the existing brick walls, reduced contact soil pressures and ceasing of increased settlements and tilting of the Cathedral towers.
Stochastic PCA-Based Bone Models from Inverse Transform Sampling: Proof of Concept for Mandibles and Proximal Femurs
Authors: Pascoletti Giulia , Aldieri Alessandra , Terzini Mara , Bhattacharya Pinaki , Calì Michele , Zanetti Elisabetta M.
Published: June 2021

Principal components analysis is a powerful technique which can be used to reduce data dimensionality. With reference to three-dimensional bone shape models, it can be used to generate an unlimited number of models, defined by thousands of nodes, from a limited (less than twenty) number of scalars. The full procedure has been here described in detail and tested. Two databases were used as input data: the first database comprised 40 mandibles, while the second one comprised 98 proximal femurs. The “average shape” and principal components that were required to cover at least 90% of the whole variance were identified for both bones, as well as the statistical distributions of the respective principal components weights. Fifteen principal components sufficed to describe the mandibular shape, while nine components sufficed to describe the proximal femur morphology. A routine has been set up to generate any number of mandible or proximal femur geometries, according to the actual statistical shape distributions. The set-up procedure can be generalized to any bone shape given a sufficiently large database of the respective 3D shapes.
Linear Dynamic Analysis of Free-Piston Stirling Engines on Operable Charge Pressure and Working Frequency along with Experimental Verifications
Authors: Kim Dong-Jun , Sim Kyuho
Published: June 2021

This paper presents a linear dynamic analysis on operable charge pressure and working frequency of free-piston Stirling engines (FPSE) along with experimental verifications. The equations of motion of the FPSE are formulated as a 2-degree-of-freedom (DOF) vibration system of the power piston (PP) and displacer piston (DP), based on the state equation of ideal gas and the isothermal Stirling cycle model. The dynamic models of FPSE we considered are the 1-DOF simple vibration model of each piston and the 2-DOF root locus model of coupled pistons. We developed a test FPSE for verification of the dynamic models and conducted a series of experiments to measure the dynamic behaviors of PP and DP under varying charge pressures for various masses and stiffnesses of the PP. As a result, both prediction models showed good agreements with experimental results. The 1-DOF vibration model was found to be simple and effective for predicting the operating frequency and charge pressure of FPSE. The root locus method showed reasonable predictions with an operation criterion of the PP–DP phase angle of 90°. In addition, the FPSE was confirmed to operate in resonant oscillations when the DP–PP phase angle is 90°, based on analysis of the force vector diagram of the two pistons.
Evaluation of Sown Cover Crops and Spontaneous Weed Flora as a Potential Reservoir of Black-Foot Pathogens in Organic Viticulture
Authors: León Maela , Berbegal Mónica , Abad-Campos Paloma , Ramón-Albalat Antonio , Caffi Tito , Rossi Vittorio , Hasanaliyeva Gultakin , Noceto Pierre Antoine , Wipf Daniel , Širca Saša , Razinger Jaka , Fragnière Anne-Laure , Kehrli Patrik , Ranca Aurora , Petrescu Anamaria , Armengol Josep
Published: June 2021

(1) Background. An extensive survey of grapevine-sown cover crops and spontaneous weed flora was conducted from 2019 to 2020 in organic vineyards in six European countries (France, Italy, Romania, Slovenia, Spain, Switzerland). Our main objective was to detect and identify the presence of Cylindrocarpon-like asexual morphs species associated with black-foot disease on their roots. (2) Methods. Fungal isolations from root fragments were performed on culture media. Cylindrocarpon-like asexual morph species were identified by analyzing the DNA sequence data of the histone H3 (his3) gene region. In all, 685 plants belonging to different botanical families and genera were analyzed. Cylindrocarpon-like asexual morphs were recovered from 68 plants (9.9% of the total) and approximately 0.97% of the plated root fragments. (3) Results. Three fungal species (Dactylonectria alcacerensis, Dactylonectria torresensis, Ilyonectria robusta) were identified. Dactylonectria torresensis was the most frequent, and was isolated from many cover crop species in all six countries. A principal component analysis with the vineyard variables showed that seasonal temperatures and organic matter soil content correlated positively with Cylindrocarpon-like asexual morphs incidence. (4) Conclusions. The presence of Cylindrocarpon-like asexual morphs on roots of cover crops suggests that they can potentially act as alternative hosts for long-term survival or to increase inoculum levels in vineyard soils.
Gene Expression Profiles Associated with Radio-Responsiveness in Locally Advanced Rectal Cancer
Authors: Lee Jeeyong , Kwon Junhye , Kim DaYeon , Park Misun , Kim KwangSeok , Bae InHwa , Kim Hyunkyung , Kong JoonSeog , Kim Younjoo , Shin UiSup , Kim EunJu
Published: June 2021

LARC patients were sorted according to their radio-responsiveness and patient-derived organoids were established from the respective cancer tissues. Expression profiles for each group were obtained using RNA-seq. Biological and bioinformatic analysis approaches were used in deciphering genes and pathways that participate in the radio-resistance of LARC. Thirty candidate genes encoding proteins involved in radio-responsiveness–related pathways, including the immune system, DNA repair and cell-cycle control, were identified. Interestingly, one of the candidate genes, cathepsin E (CTSE), exhibited differential methylation at the promoter region that was inversely correlated with the radio-resistance of patient-derived organoids, suggesting that methylation status could contribute to radio-responsiveness. On the basis of these results, we plan to pursue development of a gene chip for diagnosing the radio-responsiveness of LARC patients, with the hope that our efforts will ultimately improve the prognosis of LARC patients.
Multispectral Assessment of Sweet Pepper (Capsicum annuum L.) Fruit Quality Affected by Calcite Nanoparticles
Authors: Vidak Monika , Lazarević Boris , Petek Marko , Gunjača Jerko , Šatović Zlatko , Budor Ivica , Carović-Stanko Klaudija
Published: June 2021

Sweet pepper (Capsicum annuum L.) is one of the most important vegetable crops in the world because of the nutritional value of its fruits and its economic importance. Calcium (Ca) improves the quality of sweet pepper fruits, and the application of calcite nanoparticles in agricultural practice has a positive effect on the morphological, physiological, and physicochemical properties of the whole plant. The objectives of this study were to investigate the effect of commercial calcite nanoparticles on yield, chemical, physical, morphological, and multispectral properties of sweet pepper fruits using a combination of conventional and novel image-based nondestructive methods of fruit quality analysis. In the field trial, two sweet pepper cultivars, i.e., Šorokšari and Kurtovska kapija, were treated with commercial calcite nanoparticles (at a concentration of 3% and 5%, calcite-based foliar fertilizer (positive control), and water (negative control) three times during vegetation). Sweet pepper fruits were harvested at the time of technological and physiological maturity. Significant differences were observed between pepper cultivars as well as between harvests times. In general, application of calcite nanoparticles reduced yield and increased fruit firmness. However, different effects of calcite nanoparticles were observed on almost all properties depending on the cultivar. In Šorokšari, calcite nanoparticles and calcite-based foliar fertilizers significantly increased N, P, K, Mg, Fe, Zn, Mn, and Cu at technological maturity, as well as P, Ca, Mg, Fe, Zn, Mn, Cu, and N at physiological maturity. However, in Kurtovska kapija, the treatments increased only Ca at technological maturity and only P at physiological maturity. The effect of treatments on fruit morphological properties was observed only at the second harvest. In Šorokšari, calcite nanoparticles (3% and 5%) increased the fruit length, minimal circle area, and minimal circle radius, and it decreased the fruit width and convex hull compared to the positive and negative controls, respectively. In Kurtovska kapija, calcite nanoparticles increased the fruit width and convex hull compared to the controls. At physiological maturity, lower anthocyanin and chlorophyll indices were found in Kurtovska kapija in both treatments with calcite nanoparticles, while in Šorokšari, the opposite effects were observed.
Review of Methodological Approaches to Human Milk Small Extracellular Vesicle Proteomics
Authors: Vahkal Brett , Kraft Jamie , Ferretti Emanuela , Chung Minyoung , Beaulieu Jean-François , Altosaar Illimar
Published: June 2021

Proteomics can map extracellular vesicles (EVs), including exosomes, across disease states between organisms and cell types. Due to the diverse origin and cargo of EVs, tailoring methodological and analytical techniques can support the reproducibility of results. Proteomics scans are sensitive to in-sample contaminants, which can be retained during EV isolation procedures. Contaminants can also arise from the biological origin of exosomes, such as the lipid-rich environment in human milk. Human milk (HM) EVs and exosomes are emerging as a research interest in health and disease, though the experimental characterization and functional assays remain varied. Past studies of HM EV proteomes have used data-dependent acquisition methods for protein detection, however, improvements in data independent acquisition could allow for previously undetected EV proteins to be identified by mass spectrometry. Depending on the research question, only a specific population of proteins can be compared and measured using isotope and other labelling techniques. In this review, we summarize published HM EV proteomics protocols and suggest a methodological workflow with the end-goal of effective and reproducible analysis of human milk EV proteomes.
Health Aspects, Growth Performance, and Meat Quality of Rabbits Receiving Diets Supplemented with Lettuce Fertilized with Whey Protein Hydrolysate Substituting Nitrate
Authors: Osman Ali , Imbabi Tharwat A. , El-Hadary Abdalla , Sabeq Islam Ibrahim , Edris Shimaa N. , Merwad Abdel-Rahaman , Azab Ehab , Gobouri Adil A. , Mohammadein Amaal , Sitohy Mahmoud
Published: June 2021

Lettuce (Lactuca sativa) was grown using a foliar spray with whey protein hydrolysate (WPH) as opposed to normal nitrate fertilization. Lettuce juice was prepared from lettuce cultivated without any fertilization, nitrate fertilization, or WPH. Sixty weaned, 4-week-old male V-line rabbits with an average 455 ± 6 g body weight were randomly divided into 4 groups (n = 15) and administered different lettuce juices. Rabbits administered WPH-fertilized lettuce showed significantly higher (n = 5, p < 0.05) body weight and carcass weight than those receiving nitrate-fertilized lettuce. Rabbits administered nitrate-fertilized lettuce were associated with significantly (p < 0.05) higher levels of liver enzyme activities (AST, ALT, and ALP), bilirubin (total, direct, and indirect), and kidney biomarkers (creatinine, urea, and uric acid). Rabbits administered WPH-fertilized lettuce avoided such increases and exhibited normal levels of serum proteins. Rabbits administered nitrate-fertilized lettuce manifested significantly (p < 0.05) lower RBCs and Hb levels than that of the other groups, while those receiving WPH-fertilized lettuce showed the highest levels. Liver and kidney sections of rabbits receiving WPH-fertilized lettuce witnessed the absence of the histopathological changes induced by feeding on nitrate-fertilized lettuce and produced higher quality meat. WPH-lettuce can substitute nitrate-fertilized lettuce in feeding rabbits for better performance and health aspects.
Beneficial Effects of Mineralocorticoid Receptor Pathway Blockade against Endothelial Inflammation Induced by SARS-CoV-2 Spike Protein
Authors: Jover Eva , Matilla Lara , Garaikoetxea Mattie , Fernández-Celis Amaya , Muntendam Pieter , Jaisser Frédéric , Rossignol Patrick , López-Andrés Natalia
Published: June 2021

Background: Vascular endothelial cells activation and dysfunction mediate inflammation and abnormal coagulation in COVID-19 patients. Mineralocorticoid receptor (MR) signaling and its downstream target Galectin-3 (Gal-3) are known to mediate cardiovascular inflammation and might be involved in the pathogenesis of COVID-19 complications. Accordingly, we aimed to investigate the potential beneficial effects of MR antagonism and Gal-3 inhibition on the inflammatory response induced by SARS-CoV-2 Spike protein in human aortic endothelial cells (HAECs). Methods: HAECs were treated with recombinant SARS-COV2 Spike (S) protein. MR antagonists (namely spironolactone and eplerenone) or the Gal-3 inhibitor G3P-01 were supplemented before and after S protein challenge. HAECs supernatants were assessed by ELISA or Western blotting. Results: HAECs treated with recombinant S protein resulted in enhanced secretion of inflammatory molecules (interleukin-6, monocyte chemoattractant protein-1, interleukin-18, interleukin-27, and interferon-γ) as well as in the thrombosis marker plasminogen activator inhibitor (PAI)-1. This was prevented and reversed by both MR antagonists and G3P-01. Conclusions: These findings indicate that MR/Gal-3 pathway blockade could be a promising option to reduce endothelial inflammation in SARS-CoV-2 infection.
A Rational Designed Novel Bispecific Antibody for the Treatment of GBM
Authors: Sun Rui , Zhou Yuexian , Han Lei , Pan Zhidi , Chen Jie , Zong Huifang , Bian Yanlin , Jiang Hua , Zhang Baohong , Zhu Jianwei
Published: June 2021

Epidermal growth factor receptor variant III (EGFRvIII) is highly and specifically expressed in a subset of lethal glioblastoma (GBM), making the receptor a unique therapeutic target for GBM. Recently, bispecific antibodies (BsAbs) have shown exciting clinical benefits in cancer immunotherapy. Here, we report remarkable results for GBM treatment with a BsAb constructed by the “BAPTS” method. The BsAb was characterized through LC/MS, SEC-HPLC, and SPR. Furthermore, the BsAb was evaluated in vitro for bioactivities through FACS, antigen-dependent T-cell-mediated cytotoxicity, and a cytokine secretion assay, as well as in vivo for antitumor activity and pharmacokinetic (PK) parameters through immunodeficient NOD/SCID and BALB/c mouse models. The results indicated that the EGFRvIII-BsAb eliminated EGFRvIII-positive GBM cells by recruiting and stimulating effector T cells secreting cytotoxic cytokines that killed GBM cells in vitro. The results demonstrated the antitumor potential and long circulation time of EGFRvIII-BsAb in NOD/SCID mice bearing de2–7 subcutaneously heterotopic transplantation tumors and BALB/c mice. In conclusion, our experiments in both in vitro and in vivo have shown the remarkable antitumor activities of EGFRvIII-BsAb, highlighting its potential in clinical applications for the treatment of GBM. Additional merits, including a long circulation time and low immunogenicity, have also made the novel BsAb a promising therapeutic candidate.
Novel Pharmaceutical Strategy for Selective Abrogation of TSP1-Induced Vascular Dysfunction by Decoy Recombinant CD47 Soluble Receptor in Prophylaxis and Treatment Models
Authors: Yao Molly , Sturdivant Jalicia , Ebrahimi Aren , Ganguly Samayita , Elbayoumi Tamer
Published: June 2021

Elevated thrombospondin 1 (TSP1) is a prevalent factor, via cognate receptor CD47, in the pathogenesis of cardiovascular conditions, including ischemia-reperfusion injury (IRI) and pulmonary arterial hypertension (PAH). Moreover, TSP1/CD47 interaction has been found to be associated with platelet hyperaggregability and impaired nitric oxide response, exacerbating progression in IRI and PAH. Pathological TSP1 in circulation arises as a target of our novel therapeutic approach. Our “proof-of-concept” pharmacological strategy relies on recombinant human CD47 peptide (rh-CD47p) as a decoy receptor protein (DRP) to specifically bind TSP1 and neutralize TSP1-impaired vasorelaxation, strongly implicated in IRI and PAH. The binding of rh-CD47p and TSP1 was first verified as the primary mechanism via Western blotting and further quantified with modified ELISA, which also revealed a linear molar dose-dependent interaction. Ex vivo, pretreatment protocol with rh-CD47p (rh-CD47p added prior to TSP1 incubation) demonstrated a prophylactic effect against TSP1-impairment of endothelium-dependent vasodilation. Post-treatment set-up (TSP1 incubation prior to rh-CD47p addition), mimicking pre-existing excessive TSP1 in PAH, reversed TSP1-inhibited vasodilation back to control level. Dose titration identified an effective molar dose range (approx. ≥1:3 of tTSP1:rh-CD47p) for prevention of/recovery from TSP1-induced vascular dysfunction. Our results indicate the great potential for proposed novel decoy rh-CD47p-therapy to abrogate TSP1-associated cardiovascular complications, such as PAH.
Surface Plasmon Resonance Assay for Label-Free and Selective Detection of HIV-1 p24 Protein
Authors: Sarcina Lucia , Mangiatordi Giuseppe Felice , Torricelli Fabrizio , Bollella Paolo , Gounani Zahra , Österbacka Ronald , Macchia Eleonora , Torsi Luisa
Published: June 2021

The early detection of the human immunodeficiency virus (HIV) is of paramount importance to achieve efficient therapeutic treatment and limit the disease spreading. In this perspective, the assessment of biosensing assay for the HIV-1 p24 capsid protein plays a pivotal role in the timely and selective detection of HIV infections. In this study, multi-parameter-SPR has been used to develop a reliable and label-free detection method for HIV-1 p24 protein. Remarkably, both physical and chemical immobilization of mouse monoclonal antibodies against HIV-1 p24 on the SPR gold detecting surface have been characterized for the first time. The two immobilization techniques returned a capturing antibody surface coverage as high as (7.5 ± 0.3) × 1011 molecule/cm2 and (2.4 ± 0.6) × 1011 molecule/cm2, respectively. However, the covalent binding of the capturing antibodies through a mixed self-assembled monolayer (SAM) of alkanethiols led to a doubling of the p24 binding signal. Moreover, from the modeling of the dose-response curve, an equilibrium dissociation constant KD of 5.30 × 10−9 M was computed for the assay performed on the SAM modified surface compared to a much larger KD of 7.46 × 10−5 M extracted for the physisorbed antibodies. The chemically modified system was also characterized in terms of sensitivity and selectivity, reaching a limit of detection of (4.1 ± 0.5) nM and an unprecedented selectivity ratio of 0.02.
Real-World fNIRS Brain Activity Measurements during Ashtanga Vinyasa Yoga
Authors: Dybvik Henrikke , Steinert Martin
Published: June 2021

Functional near-infrared spectroscopy (fNIRS) is often praised for its portability and robustness towards motion artifacts. While an increasing body of fNIRS research in real-world environments is emerging, most fNIRS studies are still conducted in laboratories, and do not incorporate larger movements performed by participants. This study extends fNIRS applications in real-world environments by conducting a single-subject observational study of a yoga practice with considerable movement (Ashtanga Vinyasa Yoga) in a participant’s natural environment (their apartment). The results show differences in cognitive load (prefrontal cortex activation) when comparing technically complex postures to relatively simple ones, but also some contrasts with surprisingly little difference. This study explores the boundaries of real-world cognitive load measurements, and contributes to the empirical knowledge base of using fNIRS in realistic settings. To the best of our knowledge, this is the first demonstration of fNIRS brain imaging recorded during any moving yoga practice. Future work with fNIRS should take advantage of this by accomplishing studies with considerable real-world movement.
Parieto-Occipital Alpha and Low-Beta EEG Power Reflect Sense of Agency
Authors: Bu-Omer Hani M. , Gofuku Akio , Sato Kenji , Miyakoshi Makoto
Published: June 2021

The sense of agency (SoA) is part of psychophysiological modules related to the self. Disturbed SoA is found in several clinical conditions, hence understanding the neural correlates of the SoA is useful for the diagnosis and determining the proper treatment strategies. Although there are several neuroimaging studies on SoA, it is desirable to translate the knowledge to more accessible and inexpensive EEG-based biomarkers for the sake of applicability. However, SoA has not been widely investigated using EEG. To address this issue, we designed an EEG experiment on healthy adults (n = 15) to determine the sensitivity of EEG on the SoA paradigm using hand movement with parametrically delayed visual feedback. We calculated the power spectral density over the traditional EEG frequency bands for ten delay conditions relative to no delay condition. Independent component analysis and equivalent current dipole modeling were applied to address artifact rejection, volume conduction, and source localization to determine the effect of interest. The results revealed that the alpha and low-beta EEG power increased in the parieto-occipital regions in proportion to the reduced SoA reported by the subjects. We conclude that the parieto-occipital alpha and low-beta EEG power reflect the sense of agency.