bluuebunny/crossref_metadata_2025 huggingface dataset:
Starting and Regulating Characteristics of Electric Pump Feed System for LRE under Different Schemes
Authors: Zhou Chuang , Yu Nanjia , Wang Jue , Cai Guobiao
Published: June 2022

Liquid rocket engines (LREs) are essential power sources for access to space. Electric pump feed systems have received noteworthy attention because of their high efficiency, convenient regulation, and simple structure. In this study, an oxidant feed system with two pumps in parallel was established. The centralized parameter method and the distributed parameter method were used for modeling. The dynamic characteristics of different starting schemes and regulating schemes were obtained. The results show that the asynchronous opening of two pumps led to a pressure peak from the second stage to the third stage. Under the low operating conditions, the pump speed of the asynchronous scheme was about 13,300 r/min, the pump speed of the synchronous scheme was about 12,100 r/min, and the pump speed of the joint adjustment scheme was about 24,800 r/min. The joint adjustment of pump speed and valve opening could increase the pump speed by a factor of one-third, while maintaining the efficiency at a high level. The optimal scheme could be selected according to a genetic algorithm-based calculation process, together with the curves of the flow rate and pressure with pump speed and valve opening. This study can contribute to the application of electric pumps for liquid rocket propulsion.
O-Band Multimode Interference Coupler Power Combiner Using Slot-Waveguide Structures
Authors: Khateeb Salman , Katash Netanel , Malka Dror
Published: June 2022

Photonic transmitters that operate with a high data transfer rate (over 150 Gb/s) at the O-band range (1260–1360 nm) require at least 100 milliwatts of power to overcome the power losses that are caused by using high-speed modulators. A laser with higher power can probably handle this requirement; however, for the transmitter system, this solution can be problematic due to the nonlinear effects that can happen, which may lead to high noise in the transmitter system. Thus, to solve this issue, we propose a new design of a 2 × 1 multimode interference (MMI) power combiner using silicon nitride (SiN) slot waveguide structures. The MMI power combiner and the SiN slot waveguide structures were optimized using the full-vectorial beam propagation method (FV-BPM) and the finite difference time domain (FDTD) method. After combining two sources, high efficiency was obtained of 94.8–97.6% from the total power after a short coupling length of 109.81 µm over the O-band range with a low back reflection of 44.94 dB. Thus, the proposed device can be very useful for combining two O-band sources to gain a higher power level, which can be utilized to improve performances in transmitter systems.
Evaluation of Internal Cracks in Turbine Blade Thermal Barrier Coating Using Enhanced Multi-Scale Faster R-CNN Model
Authors: Shi Licheng , Long Yun , Wang Yuzhang , Chen Xiaohu , Zhao Qunfei
Published: June 2022

Thermal Barrier Coatings (TBCs) have good performance in heat insulation during service on turbine blades. However, the accumulated residual stress will form cracks, which can easily lead to coating failure. To ensure safe operation, it is necessary to find a method that can evaluate the health of the coating. In this paper, a non-destructive evaluation technique based on Multi-Scale Enhanced-Faster R-CNN (MSE-Faster R-CNN) is proposed. Firstly, the Visual Geometry Group Network19 layer (VGG-19) was adopted as the baseline network to find the candidate crack Region of Interest (ROI). Considering the influence of the crack on the surroundings, the ROI was expanded to obtain the context information. Secondly, a multi-scale Faster R-CNN detector was used to refine the candidate regions, and provided a comprehensive feature for better crack detection. Finally, a fusion lifetime prediction model was proposed to estimate the remaining lifetime of the TBC. Extensive experiments were conducted to evaluate the performance of the proposed method. The results demonstrated that the proposed method can accurately locate (0.898) and detect (0.806) the cracks in different scales, and the lifetime estimation result reached the best level (Root Mean Square Error (RMSE) = 2.7); there wasas also an acceptable time cost (1.63 s), and all detection conditions of the error rates were below 15%, achieving the best results among the state-of-art methods.
Theoretical Zero-Thickness Broadband Holograms Based on Acoustic Sieve Metasurfaces
Authors: Tian Ye , Zuo Shuyu , Lv Qian , Yin Guanjun , Guo Jianzhong
Published: June 2022

Acoustic holography is an essential tool for controlling sound waves, generating highly complex and customizable sound fields, and enabling the visualization of sound fields. Based on acoustic sieve metasurfaces (ASMs), this paper proposes a theoretical design approach for zero-thickness broadband holograms. The ASM is a zero-thickness rigid screen with a large number of small holes that allow sound waves to pass through and produce the desired real image in the target plane. The hole arrangement rules are determined using a genetic algorithm and the Rayleigh–Sommerfeld theory. Because the wave from a hole has no extra phase or amplitude modulation, the intractable modulation dispersion can be physically avoided, allowing the proposed ASM-based hologram to potentially function in any frequency band as long as the condition of paraxial approximation is satisfied. Using a numerical simulation based on the combination of the finite element method (FEM) and the boundary element method (BEM), this research achieves broadband holographic imaging with a good effect. The proposed theoretical zero-thickness broadband hologram may provide new possibilities for acoustic holography applications.
Triaxial Compression Fracture Characteristics and Constitutive Model of Frozen–Thawed Fissured Quasi-Sandstone
Authors: Xie Yi , Ren Jianxi , Caoxi Tailang , Chen Xu , Yun Mengchen
Published: June 2022

The artificial frozen wall crossing the water-rich sand layer is prone to failure during thawing. To study the loading fracture characteristics and damage evolution of single-fissured sandstone after thawing, quasi-sandstones with prefabricated single fissure at different angles were prepared using the sandstone of the Luohe Formation as the original rock to conduct freeze–thaw tests with various temperature differences, and triaxial compression tests were performed on the samples. Based on the distribution theory of rock micro-element strength and static elastic modulus, a damage constitutive model of single-fissured quasi-sandstone under freezing–thawing and confining pressure was established. The results show that with the decrease in freezing temperature, the amount of flake spalling on the sample surface increases, and the frost-heaving cracks of quasi-sandstone become more numerous and longer, which makes the single-fissured quasi-sandstone tend to have a more complex tensile–shear hybrid failure than a shear failure. Moreover, with the increase in fissure angle, the absolute value of the freezing temperature required to produce frost-heaving cracks increases. An S-shaped damage evolution curve corresponds to each stage of triaxial compression of single-fissured quasi-sandstone. With the decrease in freezing temperature, the strength of rock after thawing decreases, and the brittleness characteristics strengthen.
A Clutter Suppression Method Based on LSTM Network for Ground Penetrating Radar
Authors: Geng Jianrong , He Juan , Ye Hongxia , Zhan Bin
Published: June 2022

It is critical to estimate and eliminate the wavelets of ground penetrating radar (GPR), so as to optimally compensate the energy attenuation and phase distortion. This paper presents a new wavelet extraction method based on a two-layer Long Short-Term Memory (LSTM) network. It only uses several random A-scan echoes (i.e., single channel detection echo sequence) to accurately predict the wavelet of any scene. The layered detection scenes with objects buried in different region are set for the 3D Finite-Difference Time-Domain simulator to generate radar echoes as a dataset. Additionally, the simulation echoes of different scenes are used to test the performance of the neural network. Multiple experiments indicate that the trained network can directly predict the wavelets quickly and accurately, although the simulation environment becomes quite different. Moreover, the measured data collected by the Qingdao Radio Research Institute radar and the unmanned aerial vehicle ground penetrating radar are used for test. The predicted wavelets can perfectly offset the original data. Therefore, the presented LSTM network can effectively predict the wavelets and their tailing oscillations for different detection scenes. The LSTM network has obvious advantages compared with other wavelet extraction methods in practical engineering.
A Study of Eye-Tracking Gaze Point Classification and Application Based on Conditional Random Field
Authors: Bai Kemeng , Wang Jianzhong , Wang Hongfeng , Chen Xinlin
Published: June 2022

The head-mounted eye-tracking technology is often used to manipulate the motion of servo platform in remote tasks, so as to achieve visual aiming of servo platform, which is a highly integrated human-computer interaction effect. However, it is difficult to achieve accurate manipulation for the uncertain meanings of gaze points in eye-tracking. To solve this problem, a method of classifying gaze points based on a conditional random field is proposed. It first describes the features of gaze points and gaze images, according to the eye visual characteristic. An LSTM model is then introduced to merge these two features. Afterwards, the merge features are learned by CRF model to obtain the classified gaze points. Finally, the meaning of gaze point is classified for target, in order to accurately manipulate the servo platform. The experimental results show that the proposed method can classify more accurate target gaze points for 100 images, the average evaluation values Precision = 86.81%, Recall = 86.79%, We = 86.79%, these are better than relevant methods. In addition, the isolated gaze points can be eliminated, and the meanings of gaze points can be classified to achieve the accuracy of servo platform visual aiming.
An Online Detection Method for Coal Dry Screening Based on Image Processing and Fractal Analysis
Authors: He Deyi , Liu Chusheng
Published: June 2022

In coal dry screening, online detection for screening efficiency is a significant challenge. Notwithstanding, the method of image processing is strenuous to implement in this field due to the complex surface texture of shattered coal. This method identifies the fractal phenomenon before and after coal screening is discovered for the indirect detection of screening efficiency. For better fractal dimension distribution, an image denoising and filter method for wiping off the coal image surface texture is applied. Additionally, an enhanced Kirsch edge-detection algorithm is employed to obtain coal particle edges. Furthermore, the relation between fractal dimension and screening efficiency is presented by using the box-counting method. In this research, we skilfully transform the tough problem of image detection for particle size distribution into the calculation of the fractal dimension of the coal-edge image, and closely associate the fractal dimension with screening efficiency. With this method, it will be easier to predict the screening efficiency in real-time.
The Role of Splitting Phenomenon under Fracture of Low-Carbon Microalloyed X80 Pipeline Steels during Multiple Charpy Impact Tests
Authors: Kantor Matvey Matveevich , Vorkachev Konstantin Grigorievich , Bozhenov Vyacheslav Aleksandrovich , Solntsev Konstantin Aleksandrovich
Published: June 2022

The ambiguity of the splitting effect on X80 low-carbon microalloyed pipeline steels’ tendency towards brittle fracture prompted an experimental study of impact toughness scattering based on multiple Charpy impact tests in a temperature range from 20 °C to −100 °C. A fractographic analysis of a large number of fractured samples was carried out. The relationships between impact toughness, deformability and splitting characteristics were studied. A number of common features of three X80 low-carbon microalloyed pipeline steel fractures were revealed. It was experimentally established that the reason for the scattering of the impact toughness values during completely ductile fracture of specimens, as well as during fracture accompanied by the splitting formation, is the local inhomogeneity of plastic properties. The higher the susceptibility to the formation of splits for a particular steel, the lower the impact toughness. Using the electron backscatter diffraction (EBSD) technique, an uneven distribution of local plasticity in the plastic zone of impact-fractured specimens was established. A comparative analysis of specimens with equal impact toughness values at different test temperatures makes it possible to identify the mechanism of negative splitting influence compensation by the increased plasticity of certain specimen.
Determinants of Remanufacturing Adoption for Circular Economy: A Causal Relationship Evaluation Framework
Authors: Khan Shahbaz , Ali Sadia Samar , Singh Rubee
Published: June 2022

Organizations are transforming their linear models into circular models in order to become more sustainable. Remanufacturing is an essential element of the circular model; thus, there is an urgent need to adopt remanufacturing. It can offer organizations economic and environmental advantages and facilitate the transition to a circular economy (CE). Several aspects are crucial to the use of remanufacturing methods in order to transition to the CE. Therefore, in this study, we aimed to develop a framework for investigating the causal relationship among determinants of adopting remanufacturing processes for the circular economy. Through an integrated approach comprising a literature review and the Modified Delphi Method, we identified ten remanufacturing adoption determinants. The causal relationship among these determinants was established using the DEMATEL method. Furthermore, we classified these determinants into cause and effect groups. Five determinants, “consumer preferences”, “remanufacturing adoption framework”, “market opportunities”, “management commitment”, and “preferential tax policies”, belong to the cause group, and the remaining five belong to the effect group based on the effect score. To implement remanufacturing processes and transition to a circular economy, it is necessary to pay greater attention to these identified determinants, especially those that belong to the cause group. The outcomes of this study may aid management and policy makers in formulating strategies for effectively implementing remanufacturing methods within their organizations.
Editorial for the Special Issue “Atmospheric Radon Measurements, Control, Mitigation and Management”
Authors: Alexandra Cucoş (Dinu)
Published: June 2022

The Special Issue of the open-access journal Atmosphere addresses the issue of “Atmospheric Radon Measurements, Control, Mitigation and Management”, based on the global need for better management of radon and indoor air pollutants inside buildings, based on reliable research experience [...]
Software Defects Prediction Based on Hybrid Beetle Antennae Search Algorithm and Artificial Bee Colony Algorithm with Comparison
Authors: Zhang Ya , Li Tong , Li Zhen , Wu Yu-Mei , Miao Hong
Published: June 2022

Software defects are problems in software that destroy normal operation ability and reflect the quality of the software. Software fault can be predicted by the software reliability model. In this paper, the hybrid algorithm is applied to parameter estimation in software defect prediction. As a biological heuristic algorithm, BAS (Beetle Antennae Search Algorithm) has fast convergence speed and is easy to implement. ABC (Artificial Bee Colony Algorithm) is better in optimization and has strong robustness. In this paper, the BAS-ABC hybrid algorithm is proposed by mixing the two algorithms and the goal of the proposed method is to improve the convergence and stability of the algorithm. Five datasets were used to carry out the experiments, and the data results showed that the hybrid algorithm was more accurate than the single algorithm, with stronger convergence and stability, so it was more suitable for parameter estimation of the software reliability model. Meanwhile, this paper implemented the comparison between hybrid BAS + ABC and hybrid PSO + SSA, and the result shows that BAS + ABC has better performance both in convergence and stability. The comparison result shows the strong ability in estimation and prediction of software defects hybrid BAS and ABC.
Numerical Processes for Approximating Solutions of Nonlinear Equations
Authors: Regmi Samundra , Argyros Ioannis K. , George Santhosh , Argyros Christopher I.
Published: June 2022

In this article, we present generalized conditions of three-step iterative schemes for solving nonlinear equations. The convergence order is shown using Taylor series, but the existence of high-order derivatives is assumed. However, only the first derivative appears on these schemes. Therefore, the hypotheses limit the utilization of the schemes to operators that are at least nine times differentiable, although the schemes may converge. To the best of our knowledge, no semi-local convergence has been given in the setting of a Banach space. Our goal is to extend the applicability of these schemes in both the local and semi-local convergence cases. Moreover, we use our idea of recurrent functions and conditions only on the derivative or divided differences of order one that appear in these schemes. This idea can be applied to extend other high convergence multipoint and multistep schemes. Numerical applications where the convergence criteria are tested complement this article.
Feature Papers in Sensory Analysis of Beverages
Authors: Vázquez-Araújo Laura
Published: June 2022

Sensory science is a young discipline that has proven to be very useful for the food and beverage industry, not only to guarantee the quality of the organoleptic properties of raw materials and processed foods/beverages, but also to increase the probability of the success of new developments, to understand consumer response and detect potential consumer niches, and to monitor competitors [...]
A Pilot Randomized Controlled Clinical Trial Comparing Piezo Versus Conventional Rotary Surgery for Removal of Impacted Mandibular Third Molars
Authors: Saraiva Amaral Joana , Marto Carlos , Farias João , Alves Pereira Daniela , Ermida Jorge , Banaco Álvaro , Campos Felino António , Caramelo Francisco , Matos Sérgio
Published: June 2022

Background: The extraction of impacted mandibular third molars is a frequent dental surgery, interfering with patients’ quality of life. Ultrasonic surgery is an alternative to osteotomy with conventional rotary instruments. This study compares postoperative signals and symptoms after extracting impacted mandibular third molars using ultrasonic surgery or conventional rotary osteotomy. Methods: A pilot randomized controlled clinical trial was conducted. Thirty patients were randomly divided into the test group (ultrasonic technique) and a control group (conventional rotatory technique). All surgeries were timed. Swelling parameters, trismus and paraesthesia were evaluated on the day of surgery and the third, fifth and seventh postoperative days. Intraoperative bleeding was evaluated during surgery. Postoperative pain was evaluated daily by the patient through a visual analogue scale and the number of ingested analgesics. Results: Pain, swelling and trismus present beneficial results with the ultrasonic technique but without statistical significance. Intraoperative bleeding was significantly lower with ultrasonic surgery (t(28) = 3.258; p = 0.003). Operating time was significantly higher in extractions involving osteotomy and cutting crown and roots either with the conventional technique (p = 0.020) or ultrasonic technique (p = 0.039). Regardless of the surgical difficulty, no statistically significant results were detected between techniques regarding the procedure duration. Conclusions: The beneficial postoperative signs and symptoms make ultrasonic surgery a favourable therapeutic option, especially when the integrity of noble anatomical structures is the most important risk factor. Further studies with larger samples are needed to support the use of piezosurgery as a valid option for impacted mandibular third molar extraction.
Evolvability in the Cephalothoracic Structural Complexity of Aegla araucaniensis (Crustacea: Decapoda) Determined by a Developmental System with Low Covariational Constraint
Authors: Barría Erwin M. , Benítez Hugo A. , Hernández Cristián E.
Published: June 2022

The integration of complex structures is proportional to the intensity of the structural fusion; its consequences are better known than the covariational effects under less restrictive mechanisms. The synthesis of a palimpsest model based on two early parallel pathways and a later direct pathway explains the cephalothoracic complexity of decapod crustaceans. Using this model, we tested the evolvability of the developmental modularity in Aegla araucaniensis, an anomuran crab with an evident adaptive sexual dimorphism. The asymmetric patterns found on the landmark configurations suggest independent perturbations of the parallel pathways in each module and a stable asymmetry variance near the fusion by canalization of the direct pathway, which was more intense in males. The greater covariational flexibility imposed by the parallel pathways promotes the expression of gonadic modularity that favors the reproductive output in females and agonistic modularity that contributes to mating success in males. Under these divergent expressions of evolvability, the smaller difference between developmental modularity and agonistic modularity in males suggests higher levels of canalization due to a relatively more intense structural fusion. We conclude that: (1) the cephalothorax of A. araucaniensis is an evolvable structure, where parallel pathways promote sexual disruptions in the expressions of functional modularity, which are more restricted in males, and (2) the cephalothoracic palimpsest of decapods has empirical advantages in studying the developmental causes of evolution of complex structures.
Response of Cyanic and Acyanic Lettuce Cultivars to an Increased Proportion of Blue Light
Authors: Cammarisano Laura , Körner Oliver
Published: June 2022

Indoor crop cultivation systems such as vertical farms or plant factories necessitate artificial lighting. Light spectral quality can affect plant growth and metabolism and, consequently, the amount of biomass produced and the value of the produce. Conflicting results on the effects of the light spectrum in different plant species and cultivars make it critical to implement a singular lighting solution. In this study we investigated the response of cyanic and acyanic lettuce cultivars to an increased proportion of blue light. For that, we selected a green and a red leaf lettuce cultivar (i.e., ‘Aquino’, CVg, and ‘Barlach’, CVr, respectively). The response of both cultivars to long-term blue-enriched light application compared to a white spectrum was analyzed. Plants were grown for 30 days in a growth chamber with optimal environmental conditions (temperature: 20 °C, relative humidity: 60%, ambient CO2, photon flux density (PFD) of 260 µmol m−2 s−1 over an 18 h photoperiod). At 15 days after sowing (DAS), white spectrum LEDs (WW) were compared to blue-enriched light (WB; λPeak = 423 nm) maintaining the same PFD of 260 µmol m−2 s−1. At 30 DAS, both lettuce cultivars adapted to the blue light variant, though the adaptive response was specific to the variety. The rosette weight, light use efficiency, and maximum operating efficiency of PSII photochemistry in the light, Fv/Fm’, were comparable between the two light treatments. A significant light quality effect was detected on stomatal density and conductance (20% and 17% increase under WB, respectively, in CVg) and on the modified anthocyanin reflectance index (mARI) (40% increase under WB, in CVr). Net photosynthesis response was generally stronger in CVg compared to CVr; e.g., net photosynthetic rate, Pn, at 1000 µmol m−2 s−1 PPFD increased from WW to WB by 23% in CVg, compared to 18% in CVr. The results obtained suggest the occurrence of distinct physiological adaptive strategies in green and red pigmented lettuce cultivars to adapt to the higher proportion of blue light environment.
Effects of Dominance and Sprint Interval Exercise on Testosterone and Cortisol Levels in Strength-, Endurance-, and Non-Training Men
Authors: Zurek Grzegorz , Danek Natalia , Żurek Alina , Nowak-Kornicka Judyta , Żelaźniewicz Agnieszka , Orzechowski Sylwester , Stefaniak Tadeusz , Nawrat Magdalena , Kowal Marta
Published: June 2022

The aim of the study was to investigate the response of testosterone and cortisol to sprint interval exercises (SIEs) and to determine the role of dominance. The experiment was conducted in a group of 96 men, divided into endurance-training, strength-training, and non-training groups. Participants performed SIEs consisting of 5 × 10-s all-out bouts with a 50-s active recovery. Using the passive drool method, testosterone and cortisol concentrations were measured in saliva samples at rest at 10 min pre and 12 min post exercise. Participants’ heart rate (HR) was measured during the whole exercise. Dominance was assessed by the participants before the study; the rating of perceived exertion (RPE) was measured immediately after each bout. The study showed that those who trained in endurance and strength sports had significantly lower mean HRs after five acute 10-s interval bouts than those in the non-training group (p = 0.006 and p = 0.041, respectively). Dominance has an inverse relation to changes in HR; however, it has no relation to hormone response. No significant differences were observed in testosterone and cortisol changes in the endurance-training, strength-training, and non-training groups after SIE (p > 0.05), which may indicate that the exercise volume was too low.
Mammalian Melatonin Agonist Pharmaceuticals Stimulate Rhomboid Proteins in Plants
Authors: Erland Lauren A. E. , Dumigan Christopher R. , Forsyth Jillian A. , Frolova Liubov , Yasunaga Adam B. , Pun Winnie , Li Isaac T. S. , Deyholos Michael K. , Murch Susan J.
Published: June 2022

Melatonin is a human neurotransmitter and plant signalling metabolite that perceives and directs plant metabolism. The mechanisms of melatonin action in plants remain undefined. We hypothesized that roots have a melatonin-specific receptor and/or transporter that can respond to melatonin-mediating pharmaceuticals. To test this hypothesis Arabidopsis seedlings were grown with melatonin pharmaceutical receptor agonists: ramelteon and tasimelteon, and/or antagonists: luzindole and 4-P-PDOT. Ramelteon was found both to mimic and competitively inhibit melatonin metabolism in plants. Due to the higher selectivity of ramelteon for the MT1 receptor type in humans, a sequence homology search for MT1 in Arabidopsis identified the rhomboid-like protein 7 (RBL7). In physiological studies, Arabidopsis rbl7 mutants were less responsive to ramelteon and melatonin. Quantum dot visualizations of the effects of ramelteon on melatonin binding to root cell membranes revealed a potential mechanism. We propose that RBL7 is a melatonin-interacting protein that directs root architecture and growth in a mechanism that is responsive to environmental factors.
Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Promote Angiogenesis in Ischemic Stroke Mice via Upregulation of MiR-21-5p
Authors: Hu Hui , Hu Xiaowei , Li Lin , Fang Yan , Yang Yan , Gu Jingjing , Xu Jiadong , Chu Lisheng
Published: June 2022

Exosomes derived from bone mesenchymal stem cells (BMSC-Exos) are one of the main factors responsible for the therapeutic effects of BMSCs. The study aimed to investigate whether BMSC-Exos could promote angiogenesis in ischemic stroke mice via miR-21-5p. In ischemic stroke mice, the therapeutic effects of BMSC-Exos were evaluated by neurological functions and infarct volume. Microvessel density was detected by BrdU/vWF immunofluorescence staining. In in vitro experiments, the proangiogenic effects of BMSC-Exos were assessed via proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). The miR-21-5p inhibitor was transfected into BMSCs using Lipofectamine 2000. miR-21-5p expression was detected by qRT-PCR. The expression levels of VEGF, VEGFR2, Ang-1, and Tie-2 were determined by Western blot. BMSC-Exos significantly improved neurological functions and reduced infarct volume, upregulated microvessel density, and miR-21-5p expression after cerebral ischemia. In vitro assays revealed that BMSC-Exos enhanced HUVECs functions including proliferation, migration, and tube formation. BMSC-Exos increased the expression levels of VEGF, VEGFR2, Ang-1, and Tie-2. However, the proangiogenic effects of BMSC-Exos on HUVECs were reversed by the miR-21-5p inhibitor. These results suggest that BMSC-Exos could promote angiogenesis via miR-21-5p upregulation, making them an attractive treatment strategy for stroke recovery.
In Silico Discovery and Optimisation of a Novel Structural Class of Hsp90 C-Terminal Domain Inhibitors
Authors: Zajec Živa , Dernovšek Jaka , Gobec Martina , Tomašič Tihomir
Published: June 2022

Hsp90 is a promising target for the development of novel agents for cancer treatment. The N-terminal Hsp90 inhibitors have several therapeutic limitations, the most important of which is the induction of heat shock response, which can be circumvented by targeting the allosteric binding site on the C-terminal domain (CTD) of Hsp90. In the absence of an Hsp90—CTD inhibitor co-crystal structure, the use of structure-based design approaches for the Hsp90 CTD is difficult and the structural diversity of Hsp90 CTD inhibitors is limited. In this study, we describe the discovery of a novel structural class of Hsp90 CTD inhibitors. A structure-based virtual screening was performed by docking a library of diverse compounds to the Hsp90β CTD binding site. Three selected virtual hits were tested in the MCF-7 breast cancer cell line, with compound TVS-23 showing antiproliferative activity with an IC50 value of 26.4 ± 1.1 µM. We report here the optimisation, synthesis and biological evaluation of TVS-23 analogues. Several analogues showed significantly enhanced antiproliferative activities in MCF-7 breast cancer and SK-N-MC Ewing sarcoma cell lines, with 7l being the most potent (IC50 = 1.4 ± 0.4 µM MCF-7; IC50 = 2.8 ± 0.4 µM SK-N-MC). The results of this study highlight the use of virtual screening to expand the structural diversity of Hsp90 CTD inhibitors and provide new starting points for further development.
Improvement of Biomass and Phycoerythrin Production by a Strain of Rhodomonas sp. Isolated from the Tunisian Coast of Sidi Mansour
Authors: Derbel Hana , Elleuch Jihen , Tounsi Latifa , Nicolo Marco Sebastiano , Rizzo Maria Giovanna , Michaud Philippe , Fendri Imen , Abdelkafi Slim
Published: June 2022

Microalgae are photoautotrophic microorganisms known as producers of a large variety of metabolites. The taxonomic diversity of these microorganisms has been poorly explored. In this study, a newly isolated strain was identified based on the 18S rRNA encoding gene. The phylogenetic analysis showed that the isolated strain was affiliated with the Rhodomonas genus. This genus has greatly attracted scientific attention according to its capacity to produce a large variety of metabolites, including phycoerythrin. Growth and phycoerythrin production conditions were optimized using a Plackett–Burman design and response surface methodology. An expression profile analysis of the cpeB gene, encoding the beta subunit of phycoerythrin, was performed by qRT-PCR under standard and optimized culture conditions. The optimization process showed that maximum cell abundance was achieved under the following conditions: CaCl2 = 2.1328 g/L, metal solution = 1 mL/L, pH = 7 and light intensity = 145 μmol photons/m2/s, whereas maximum phycoerythrin production level occurred when CaCl2 = 1.8467 g/L, metal solution = 1 mL/L, pH = 7 and light intensity = 157 μmol/m2/s. In agreement, positive transcriptional regulation of the cpeB gene was demonstrated using qRT-PCR. This study showed the successful optimization of abiotic conditions for highest growth and phycoerythrin production, making Rhodomonas sp. suitable for several biotechnological applications.
Modeling the Competition between Misfolded Aβ Conformers That Produce Distinct Types of Amyloid Pathology in Alzheimer’s Disease
Authors: Xu Guilian , Fromholt Susan , Borchelt David R.
Published: June 2022

The amyloid pathology characteristic of Alzheimer’s disease (AD) can be broadly classified as either fibrillary amyloid or diffuse amyloid. Fibrillary amyloid is found in cored-neuritic deposits, fibrillar deposits, and vascular deposits, and binds strongly to the amyloid revealing dyes Thioflavin-S or Congo Red. Diffuse amyloid can appear as wispy dispersed deposits or compact tufted deposits dispersed in neuropil, and binds amyloid dyes weakly if at all. In AD brains, both types of pathology are detected. Homogenates from AD brains, or the brains of transgenic mice modeling AD-amyloidosis, have been used to seed pathology in vulnerable host transgenic models. These studies suggest that pathologies may arise from distinct conformers or strains of misfolded Aβ, similar to propagating prions. Using Aβ strains sourced from four different AD-amyloidosis models, we injected pathological seeds into the brains of newborn mice from three different transgenic hosts with distinctive Aβ pathologies. Two of the seeding sources were from mice that primarily develop cored-neuritic Aβ deposits (cored strain) while the other two seeding sources were from mice that develop diffuse Aβ deposits (diffuse strain). These seeds were injected into host APP mice in which the resident strain was either diffuse or cored-neuritic pathology. Seeding-homogenates were injected into the brains of newborn mice to initiate propagation as early as possible. Depending upon the level of transgene expression in the host, we show that the injected strains of misfolded Aβ from the seeding homogenate were able to outcompete the resident strain of the APP host model. In serial passaging experiments, it appeared that the diffuse strain was more easily propagated than the cored strain. Collectively, our studies align with the idea that different types of Aβ pathology in AD brains arise from different populations of Aβ conformers that compete to populate the brain.
Compositional Bias of Intrinsically Disordered Proteins and Regions and Their Predictions
Authors: Zhao Bi , Kurgan Lukasz
Published: June 2022

Intrinsically disordered regions (IDRs) carry out many cellular functions and vary in length and placement in protein sequences. This diversity leads to variations in the underlying compositional biases, which were demonstrated for the short vs. long IDRs. We analyze compositional biases across four classes of disorder: fully disordered proteins; short IDRs; long IDRs; and binding IDRs. We identify three distinct biases: for the fully disordered proteins, the short IDRs and the long and binding IDRs combined. We also investigate compositional bias for putative disorder produced by leading disorder predictors and find that it is similar to the bias of the native disorder. Interestingly, the accuracy of disorder predictions across different methods is correlated with the correctness of the compositional bias of their predictions highlighting the importance of the compositional bias. The predictive quality is relatively low for the disorder classes with compositional bias that is the most different from the “generic” disorder bias, while being much higher for the classes with the most similar bias. We discover that different predictors perform best across different classes of disorder. This suggests that no single predictor is universally best and motivates the development of new architectures that combine models that target specific disorder classes.
Cysteine Oxidation Promotes Dimerization/Oligomerization of Circadian Protein Period 2
Authors: Baidanoff Fernando Martin , Trebucq Laura Lucía , Plano Santiago Andrés , Eaton Phillip , Golombek Diego Andrés , Chiesa Juan José
Published: June 2022

The molecular circadian clock is based on a transcriptional/translational feedback loop in which the stability and half-life of circadian proteins is of importance. Cysteine residues of proteins are subject to several redox reactions leading to S-thiolation and disulfide bond formation, altering protein stability and function. In this work, the ability of the circadian protein period 2 (PER2) to undergo oxidation of cysteine thiols was investigated in HEK-293T cells. PER2 includes accessible cysteines susceptible to oxidation by nitroso cysteine (CysNO), altering its stability by decreasing its monomer form and subsequently increasing PER2 homodimers and multimers. These changes were reversed by treatment with 2-mercaptoethanol and partially mimicked by hydrogen peroxide. These results suggest that cysteine oxidation can prompt PER2 homodimer and multimer formation in vitro, likely by S-nitrosation and disulphide bond formation. These kinds of post-translational modifications of PER2 could be part of the redox regulation of the molecular circadian clock.
The Current Status of Molecular Biomarkers for Inflammatory Bowel Disease
Authors: Alghoul Zahra , Yang Chunhua , Merlin Didier
Published: June 2022

Diagnosis and prognosis of inflammatory bowel disease (IBD)—a chronic inflammation that affects the gastrointestinal tract of patients—are challenging, as most clinical symptoms are not specific to IBD, and are often seen in other inflammatory diseases, such as intestinal infections, drug-induced colitis, and monogenic diseases. To date, there is no gold-standard test for monitoring IBD. Endoscopy and imaging are essential diagnostic tools that provide information about the disease’s state, location, and severity. However, the invasive nature and high cost of endoscopy make it unsuitable for frequent monitoring of disease activity in IBD patients, and even when it is possible to replace endoscopy with imaging, high cost remains a concern. Laboratory testing of blood or feces has the advantage of being non-invasive, rapid, cost-effective, and standardizable. Although the specificity and accuracy of laboratory testing alone need to be improved, it is increasingly used to monitor disease activity or to diagnose suspected IBD cases in combination with endoscopy and/or imaging. The literature survey indicates a dearth of summarization of biomarkers for IBD testing. This review introduces currently available non-invasive biomarkers of clinical importance in laboratory testing for IBD, and discusses the trends and challenges in the IBD biomarker studies.
Comparative Adverse Kidney Outcomes in Women Receiving Raloxifene and Denosumab in a Real-World Setting
Authors: Chen Hsin-Wei , Hsu Chien-Ning , Lee Yueh-Ting , Fu Chung-Ming , Wang Shih-Wei , Huang Chiang-Chi , Li Lung-Chih
Published: June 2022

Both osteoporosis and kidney diseases are common and intercorrelate to increase morbidity and mortality in elderly women. This study aimed to compare adverse kidney outcome between women initiated with denosumab and a matched group of raloxifene initiators using propensity score matching methods in a large healthcare delivery system in Taiwan. The risks of adverse kidney outcomes were estimated using Cox proportional hazard regression and the change in kidney function over time was analyzed using the linear mixed model. A total of 9444 (4722 in each group) women were identified who matched the inclusion criteria between January 2003 and December, 2018. Denosumab use was significantly associated with higher risk of eGFR decline ≥ 30% from baseline than raloxifene use (aHR: 1.26; 95% CI: 1.16–1.36, p < 0.0001). The mean change in eGFR over time was 1.24 mL/min/1.73 m2 per year in the denosumab group and 0.45 mL/min/1.73 m2 per year in the raloxifene group (p = 0.0004). However, the risks of acute kidney injury (10.53%) and chronic dialysis (0.66%) in this study cohort were not significantly different for the two anti-osteoporosis treatments. Close monitoring of the residual kidney function and treatment effect is needed in those with denosumab.
High-Density Lipoprotein Changes in Alzheimer’s Disease Are APOE Genotype-Specific
Authors: Hong Brian V. , Zheng Jingyuan , Agus Joanne K. , Tang Xinyu , Lebrilla Carlito B. , Jin Lee-Way , Maezawa Izumi , Erickson Kelsey , Harvey Danielle J. , DeCarli Charles S. , Mungas Dan M. , Olichney John M. , Farias Sarah T. , Zivkovic Angela M.
Published: June 2022

High-density lipoproteins (HDL) play a critical role in cholesterol homeostasis. Apolipoprotein E (APOE), particularly the E4 allele, is a significant risk factor for Alzheimer’s disease but is also a key HDL-associated protein involved in lipid transport in both the periphery and central nervous systems. The objective was to determine the influence of the APOE genotype on HDL function and size in the context of Alzheimer’s disease. HDL from 194 participants (non-demented controls, mild cognitive impairment, and Alzheimer’s disease dementia) were isolated from the plasma. The HDL cholesterol efflux capacity (CEC), lecithin-cholesterol acyltransferase (LCAT) activity, and particle diameter were measured. Neuropsychological test scores, clinical dementia rating, and magnetic resonance imaging scores were used to determine if cognition is associated with HDL function and size. HDL CEC and LCAT activity were reduced in APOE3E4 carriers compared to APOE3E3 carriers, regardless of diagnosis. In APOE3E3 carriers, CEC and LCAT activity were lower in patients. In APOE3E4 patients, the average particle size was lower. HDL LCAT activity and particle size were positively correlated with the neuropsychological scores and negatively correlated with the clinical dementia rating. We provide evidence for the first time of APOE genotype-specific alterations in HDL particles in Alzheimer’s disease and an association between HDL function, size, and cognitive function.
Mitochondrial Ribosome Dysfunction in Human Alveolar Type II Cells in Emphysema
Authors: Karim Loukmane , Lin Chih-Ru , Kosmider Beata , Criner Gerard , Marchetti Nathaniel , Bolla Sudhir , Bowler Russell , Bahmed Karim
Published: June 2022

Pulmonary emphysema is characterized by airspace enlargement and the destruction of alveoli. Alveolar type II (ATII) cells are very abundant in mitochondria. OXPHOS complexes are composed of proteins encoded by the mitochondrial and nuclear genomes. Mitochondrial 12S and 16S rRNAs are required to assemble the small and large subunits of the mitoribosome, respectively. We aimed to determine the mechanism of mitoribosome dysfunction in ATII cells in emphysema. ATII cells were isolated from control nonsmokers and smokers, and emphysema patients. Mitochondrial transcription and translation were analyzed. We also determined the miRNA expression. Decreases in ND1 and UQCRC2 expression levels were found in ATII cells in emphysema. Moreover, nuclear NDUFS1 and SDHB levels increased, and mitochondrial transcribed ND1 protein expression decreased. These results suggest an impairment of the nuclear and mitochondrial stoichiometry in this disease. We also detected low levels of the mitoribosome structural protein MRPL48 in ATII cells in emphysema. Decreased 16S rRNA expression and increased 12S rRNA levels were observed. Moreover, we analyzed miR4485-3p levels in this disease. Our results suggest a negative feedback loop between miR-4485-3p and 16S rRNA. The obtained results provide molecular mechanisms of mitoribosome dysfunction in ATII cells in emphysema.
Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice
Authors: Zhang Jia-He , Tasaki Takashi , Tsukamoto Manabu , Wang Ke-Yong , Kubo Kin-ya , Azuma Kagaku
Published: June 2022

The hippocampus plays an important role in maintaining normal cognitive function and is closely associated with the neuropathogenesis of dementia. Wnt signaling is relevant to neuronal development and maturation, synaptic formation, and plasticity. The role of Wnt10a in hippocampus-associated cognition, however, is largely unclear. Here, we examined the morphological and functional alterations in the hippocampus of Wnt10a-knockout (Wnt10a-/-) mice. Neurobehavioral tests revealed that Wnt10a-/- mice exhibited spatial memory impairment and anxiety-like behavior. Immunostaining and Western blot findings showed that the protein expressions of β-catenin, brain-derived neurotrophic factor, and doublecortin were significantly decreased and that the number of activated microglia increased, accompanied by amyloid-β accumulation, synaptic dysfunction, and microglia-associated neuroinflammation in the hippocampi of Wnt10a-/- mice. Our findings revealed that the deletion of Wnt10a decreased neurogenesis, impaired synaptic function, and induced hippocampal neuroinflammation, eventually leading to hippocampal neurodegeneration and memory deficit, possibly through the β-catenin signaling pathway, providing a novel insight into preventive approaches for hippocampus-dependent cognitive impairment.
Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury
Authors: Wu Siyu , García-Rama Concepción , Romero-Ramírez Lorenzo , de Munter Johannes P. J. M. , Wolters Erik Ch. , Kramer Boris W. , Mey Jörg
Published: June 2022

The bile acid tauroursodeoxycholic acid (TUDCA) reduces cell death under oxidative stress and inflammation. Implants of bone marrow-derived stromal cells (bmSC) are currently under investigation in clinical trials of spinal cord injury (SCI). Since cell death of injected bmSC limits the efficacy of this treatment, the cytoprotective effect of TUDCA may enhance its benefit. We therefore studied the therapeutic effect of TUDCA and its use as a combinatorial treatment with human bmSC in a rat model of SCI. A spinal cord contusion injury was induced at thoracic level T9. Treatment consisted of i.p. injections of TUDCA alone or in combination with one injection of human bmSC into the cisterna magna. The recovery of motor functions was assessed during a surveillance period of six weeks. Biochemical and histological analysis of spinal cord tissue confirmed the anti-inflammatory activity of TUDCA. Treatment improved the recovery of autonomic bladder control and had a positive effect on motor functions in the subacute phase, however, benefits were only transient, such that no significant differences between vehicle and TUDCA-treated animals were observed 1–6 weeks after the lesion. Combinatorial treatment with TUDCA and bmSC failed to have an additional effect compared to treatment with bmSC only. Our data do not support the use of TUDCA as a treatment of SCI.