bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Excitation Estimation for Ocean Wave Energy Generators Based on Extended Kalman Filtering
Authors: Zhang Yuchen , Zhang Zhenquan , Wang Jun , Qin Jian , Huang Shuting , Xue Gang , Liu Yanjun
Published: February 2024

Wave energy generation methods have significant energy costs. The implementation of sophisticated control techniques in wave energy generators can lower the cost of power generation by optimizing the energy recovered from wave energy converters (WECs). To determine control inputs, most control systems rely on knowledge of the wave excitation force, including information on past, present, and future excitation forces. For the excitation of WEC devices, wave excitation force can only be inferred and predicted because it is an unmeasurable quantity. One of the more widely used observers in wave excitation estimates at the moment is the Kalman filter, but its use is primarily restricted to linear Kalman filtering. The mooring system is an integral component of floating wave energy producers. The mooring force of the device is actually nonlinear; however, the majority of current studies on excitation estimates for wave energy producers based on Kalman filter methods employ an ideal motion model based on the linearization of the mooring force. This paper, in an attempt to make things more realistic, creates a WEC system with highly nonlinear mooring forces, suggests a way to build a wave excitation force estimator for a nonlinear WEC system using the extended Kalman filtering method, and assesses the impact of various factors, such as measurement noise, random phase, and the number of equal-energy methods dividing the frequency, on the accuracy of the wave excitation force estimate.
Celerity of Ice Breakup Front in the Regulated Peace River, Canada, and Implications for the Recharge of the Peace–Athabasca Delta
Authors: Beltaos Spyros
Published: February 2024

Timely release of flow from upstream hydropower generation facilities on the Peace River can enhance potential ice-jam flooding near the drying Peace–Athabasca Delta (PAD), a Ramsar wetland of international importance and homeland to Indigenous Peoples. An important consideration in deciding whether and when to commence a release is the celerity of the breakup front as it advances along the Peace River. Relevant historical data for a key stretch of the river are analyzed to determine average celerities, which can vary by an order of magnitude from year to year. Seven breakup events are identified that might have been candidates for a release, and the predictability of associated celerities is explored in terms of antecedent hydroclimatic variables, including cumulative winter snowfall, snow water equivalent on 1 April, ice cover thickness, coldness of the winter, and freezeup level. It is shown that celerity can be predicted to within a factor of two or less, with the freezeup level giving the best results. Three of the seven “promising” events culminated in PAD floods and were associated with the three highest celerities. The empirical findings are shown to generally align with physical understanding of breakup driving and resisting factors.
Water Balance Characteristics of the Salix Shelterbelt in the Kubuqi Desert
Authors: Han Qingchi , Sun Kai , Wang Haichao , Pei Zhiyong , Chen Hongwei , Yang Jianjun , Sun Xiaotian
Published: February 2024

Water shortages are the main factor restricting the survival and construction of shelterbelts in sandy areas. Comprehensive analysis of the water balance characteristics of forest stands is crucial for scientifically understanding and regulating the water supply of shelterbelts in sandy areas and formulating appropriate vegetation cultivation and restoration strategies. We simultaneously monitored outer-forest precipitation, canopy interception, stemflow, throughfall, forest transpiration, understory evapotranspiration, and soil moisture content changes in the Salix forest in the Kubuqi Desert during the main growing season (June–October) of 2022. The results showed that the total evapotranspiration of the forest was 185.62 mm, and the components and their proportions of precipitation during the same period were as follows: forest floor evapotranspiration, 94.43 mm (35.88%); stand transpiration, 68.34 mm (25.97%); and canopy interception, 22.85 mm (8.68%). Based on the water balance of the 0–60 cm soil layer and by integrating the changes in soil water storage and the influence of external water transport, the net runoff of the forestland was calculated to be approximately 77.58 mm; that is, the water balance requirements for growth were met. In the future, appropriate irrigation and supplementation can be carried out in June and July to ensure healthier growth in the shelterbelt, and plant photosynthesis and internal physiology can be further studied for cultivation in other desert areas.
Assessing the Interactive Effects of High Salinity and Stocking Density on the Growth and Stress Physiology of the Pacific White Shrimp Litopenaeus vannamei
Authors: Liu Fei , Sun Jinfeng , Long Jinnan , Sun Lichao , Liu Chang , Wang Xiaofan , Zhang Long , Hao Pengyuan , Wang Zhongkai , Cui Yanting , Wang Renjie , Li Yuquan
Published: February 2024

This study was conducted to evaluate the effects of high salinity combined with stocking density on Litopenaeus vannamei. Three salinity gradients, namely, 28 g/L, 36 g/L, and 44 g/L, and two stocking densities, namely, 300 and 600 shrimp/m3, were used to analyze the synergistic effect of high salinity and stocking density on the growth performance, digestibility, and energy budgets of L. vannamei. The experimental testing period lasted 45 days. The research results showed that a salinity level of 36 g/L was the most suitable salinity level for shrimp growth under both high and low stocking densities. The body weight, specific growth rate, and relative weight gain of the shrimp in the 36 g/L salinity group were significantly higher than those in the other two salinity groups under both high and low stocking densities. The high-density farming group with 600 shrimp/m3 exhibited a significant inhibition of shrimp growth compared to the low-density group under the same salinity conditions. The activities of amylase, lipase, and protease in the high-density-group shrimp gradually decreased with an increase in salinity, and the three digestive enzymes had the same overall effect of changing trends. This indicates that under high-density farming conditions, the increase in salinity is not conducive to the digestive function of shrimps. At the same time, the proportion of respiratory energy to feeding energy gradually decreased in the high-density group and with the increase in salinity. However, under the same salinity conditions, the higher the stocking density, the higher the energy consumed by respiration compared to the low-density group. In addition, the expression of the growth-related gene’s small nuclear ribonucleoprotein polypeptide G (SNRPG) under high stocking density was significantly lower than that in the low-density group at a salinity of 28 g/L, and ribosomal protein L7 (RPL7) expression was also significantly lower under high stocking density than that in the low-density group at a salinity of 44 g/L. The expression levels of molting-related genes retinoid X receptor (RXR), ecdysone receptor (ECR), and ecdysone-induced protein 75 (E75) were significantly higher in the 36 g/L salinity group compared with the other two salinity groups under high-stocking-density treatment. The findings indicate that the synergistic effects of salinity and stocking density have a significant impact on the growth of L. vannamei, and excessive salinity would inhibit its growth in the process of high-density culturing.
Effect of Dissolved Carbon Dioxide on Cavitation in a Circular Orifice
Authors: Safaei Sina , Mehring Carsten
Published: February 2024

In this work, we investigate the effect of dissolved gas concentration on cavitation inception and cavitation development in a transparent sharp-edged orifice, similar to that previously analyzed by Nurick in the context of liquid injectors. The working liquid is water, and carbon dioxide is employed as a non-condensable dissolved gas. Cavitation inception points are determined for different dissolved gas concentration levels by measuring wall-static pressures just downstream of the orifice contraction and visually observing the onset of a localized (vapor) bubble cloud formation and collapse. Cavitation onset correlates with a plateau in wall-static pressure measurements as a function of a cavitation number. An increase in the amount of dissolved carbon dioxide is found to increase the cavitation number at which the onset of cavitation occurs. The transition from cloud cavitation to extended-sheet or full cavitation along the entire orifice length occurs suddenly and is shifted to higher cavitation numbers with increasing dissolved gas content. Volume flow rate measurements are performed to determine the change in the discharge coefficient with the cavitation number and dissolved gas content for the investigated cases. CFD analyses are carried out based on the cavitation model by Zwart et al. and the model by Yang et al. to account for non-condensable gases. Discharge coefficients obtained from the numerical simulations are in good agreement with experimental values, although they are slightly higher in the cavitating case. The earlier onset of fluid cavitation (i.e., cavitation inception at higher cavitation numbers) with increasing dissolved carbon dioxide content is not predicted using the employed numerical model.
Evaluation of Arabica Coffee Fermentation Using Machine Learning
Authors: Rocha Renata A. R. , Cruz Marcelo A. D. da , Silva Lívia C. F. , Costa Gisele X. R. , Amaral Laurence R. , Bertarini Pedro L. L. , Gomes Matheus S. , Santos Líbia D.
Published: February 2024

This study explores the variances in the organic, chemical, and sensory attributes of fermented coffee beans, specifically examining how post-harvest processes influence cup quality. Coffee fruits from the Catuaí IAC-144 variety were processed using both natural coffee (NC) and pulped coffee (PC) methods. The fruits were then subjected to self-induced anaerobic fermentation (SIAF) using one of the following fermentation methods: solid-state fermentation (SSF) or submerged fermentation (SMF). Within these methods, either spontaneous fermentation (SPF) or starter culture fermentation (SCF) was applied. Each method was conducted over periods of 24, 48, and 72 h. For this purpose, two-hundred-liter bioreactors were used, along with two control treatments. Numerous parameters were monitored throughout the fermentation process. A comprehensive chemical profiling and sensory analysis, adhering to the guidelines of the Specialty Coffee Association, were conducted to evaluate the influence of these fermentation processes on the flavor, aroma, and body characteristics of the coffee beverage across multiple dimensions. Data analysis and predictive modeling were performed using machine learning techniques. This study found that NC exhibited a higher production of acids (citric, malic, succinic, and lactic) compared to PC, resulting in distinct chemical and sensory profiles. The decision tree showed that fructose and malic and succinic acids were identified as the main factors enhancing sensory notes during cupping. SMF promoted higher concentrations of lactic acid, while SSF led to increased ethanol content. Consequently, the SIAF process enhances the sensory quality of coffee, adding value to the product by generating diverse sensory profiles.
Food Safety and Management System Audits in Food Retail Chain Stores in Greece
Authors: Psomatakis Michalis , Papadimitriou Konstantinos , Souliotis Andreas , Drosinos Eleftherios H. , Papadopoulos Georgios
Published: February 2024

The present study aimed to assess the performance of food safety management systems in food retail stores via audits to reveal potential areas of improvement and to find out possible corrective actions to suggest to the top management. Two cycles of on-site audits took place in 106 stores to assess the requirements and hygiene conditions. After the first cycle of audits, improvements were suggested to the top management, and a second cycle of audits took place after a reasonable time. In the checklist, we recorded the temperatures of retail refrigerators and the scores from the inspection of hygiene and HACCP documentation. In the A′ audit, the percentage of stores that had higher temperatures than the critical limits was equal to 51%, and those temperatures occurred in the refrigerators for salads, followed by the refrigerators for deli meat, yogurts and desserts. In the B′ audit, only the refrigerators for salads exhibited percentages that were statistically significant lower (p-value < 0.05), and the stores were improved after the audit. High percentages of high-scoring stores were observed in the A′ and B′ audit in the inspection of HACCP documentation, although there was not a statistically significant improvement observed (p-value > 0.05). In the hygiene inspection, statistically significant improvement with 95% confidence appeared for “Refrigerator’s products appearance”, “Storage cleanliness”, and “Grocery shelf cleanliness”. The highest number of non-conformities without statistically significant improvement was found for “Checking temperatures of the receiving products” and “Labeling of fruit store products”, with the percentages being lower than 15% in both of the audit cycles. Many employees of the stores did not check and record the temperatures of receiving products from suppliers. In addition, the storage of spoiled products beneath fresh products for selling in the same refrigerator is not a good practice. Greater efforts must be made by top management and employees to maintain and distribute food products in the best and safest possible hygiene conditions.
Influence of Dietary Fibre and Protein Fractions on the Trace Element Bioaccessibility of Turnip Tops (Brassica rapa) Growing under Mediterranean Conditions
Authors: Cámara-Martos Fernando
Published: February 2024

The objective of this work was to study the influence of three dietary fibre fractions (pectin, gum arabic and cellulose) and three protein fractions (casein, lactalbumin and soy) on the trace element bioaccessibility (Fe, Mn, Ni, Se and Zn) of turnip tops (B. rapa subsp. Rapa) growing under Mediterranean conditions. Then, it aimed to promote the use of this vegetable not only for direct fresh consumption but also as a main ingredient in the development of food mixtures. The results showed that soluble fibre fractions, such as pectin and gum arabic, can enhance the bioaccessibility of trace elements, such as Fe, Mn, Se and Zn. This effect was not proved for cellulose (an insoluble fibre fraction), in which, at best, no bioaccessibility effect was observed. Regarding the protein fractions, with the exception of Se, caseins and lactalbumin had a neutral effect on improving the trace element bioaccessibility. This did not hold true for soy protein, in which a considerable improvement in the bioaccessibility of Fe, Mn, Se and Zn was determined.
Effect of Konjac Glucomannan on Structure, Physicochemical Properties, and In Vitro Digestibility of Yam Starch during Extrusion
Authors: Hao Mengshuang , Zhu Xiaopei , Ji Xiaolong , Shi Miaomiao , Yan Yizhe
Published: February 2024

In this study, the effect of konjac glucomannan (KGM, 0–5%) on the structure, physicochemical properties, and in vitro digestibility of extruded yam starch (EYS) was investigated. The EYS became rougher on the surface and the particle size increased as observed using scanning electron microscopy and particle size analysis. X-ray diffraction and Raman results revealed that the relative crystallinity (18.30% to 22.30%) of EYS increased, and the full width at half maxima at 480 cm−1 decreased with increasing KGM content, indicating the increment of long-range and short-range ordered structure. Differential scanning calorimetry and rheological results demonstrated that KGM enhanced thermal stability and the gel strength of EYS due to enhanced interaction between KGM and YS molecules. Additionally, a decrease in the swelling power and viscosity of EYS was observed with increased KGM content. The inclusion of KGM in the EYS increased the resistant starch content from 11.89% to 43.51%. This study provides a dual-modified method using extrusion and KGM for modified YS with high thermal stability, gel strength, and resistance to digestion.
Milk Whey Protein Fibrils—Effect of Stirring and Heating Time
Authors: Rathod Gunvantsinh , Amamcharla Jayendra
Published: February 2024

Milk whey proteins, which are derived from skim milk through membrane filtration, exhibit valuable functional properties when transformed into a fibrillar form. This conversion enhances their suitability for various applications, including thickening, gelling, emulsification, and foaming. However, reported fibrillation methods have longer heating times, which may not be economical for the dairy industry. To address these challenges, the current study was undertaken with the objective of reducing the time required for fibril formation. In this study, 2% milk whey protein isolate (mWPI) solution at pH 2 was heated with static and stirring heating conditions at 80 °C for 20 h to convert milk whey proteins into fibrils. Fibrils were observed using the thioflavin T value, transmission electron microscopy, Tricine SDS-PAGE, rheology, and protein oxidation. Results suggest that stirring heating conditions with 14 h heating time produced fibrils with good morphology compared to static heating, showing a 6 h reduction compared to an earlier reported 80 °C for 20 h heating time. Also, stirring heating produced a uniform and homogeneous fibril solution compared to the static heating method. Gentle stirring during heating can also help to scale up fibril production in an industrial setup. The fibrillation method with processing intervention will help to produce fibrils with enhanced functionality at the pilot and industrial scales.
Fabrication of Sodium Trimetaphosphate-Based PEDOT:PSS Conductive Hydrogels
Authors: Reynolds Madelyn , Stoy Lindsay M. , Sun Jindi , Opoku Amponsah Prince Emmanuel , Li Lin , Soto Misael , Song Shang
Published: February 2024

Conductive hydrogels are highly attractive for biomedical applications due to their ability to mimic the electrophysiological environment of biological tissues. Although conducting polymer polythiophene-poly-(3,4-ethylenedioxythiophene) (PEDOT) and polystyrene sulfonate (PSS) alone exhibit high conductivity, the addition of other chemical compositions could further improve the electrical and mechanical properties of PEDOT:PSS, providing a more promising interface with biological tissues. Here we study the effects of incorporating crosslinking additives, such as glycerol and sodium trimetaphosphate (STMP), in developing interpenetrating PEDOT:PSS-based conductive hydrogels. The addition of glycerol at a low concentration maintained the PEDOT:PSS conductivity with enhanced wettability but decreased the mechanical stiffness. Increasing the concentration of STMP allowed sufficient physical crosslinking with PEDOT:PSS, resulting in improved hydrogel conductivity, wettability, and rheological properties without glycerol. The STMP-based PEDOT:PSS conductive hydrogels also exhibited shear-thinning behaviors, which are potentially favorable for extrusion-based 3D bioprinting applications. We demonstrate an interpenetrating conducting polymer hydrogel with tunable electrical and mechanical properties for cellular interactions and future tissue engineering applications.
Engineering Geological and Geophysical Investigations to Characterise the Unstable Rock Slope of the Sopu Promontory (Gozo, Malta)
Authors: Pistillo Davide , Colica Emanuele , D’Amico Sebastiano , Farrugia Daniela , Feliziani Federico , Galone Luciano , Iannucci Roberto , Martino Salvatore
Published: February 2024

Different engineering geological and geophysical investigations were performed at the Sopu promontory in the island of Gozo (Malta), involved in an impressive lateral spreading process due to the superimposition of a stiff limestone (ULC) on a ductile clay (BC). The applied techniques include: traditional geological and engineering geological surveys, unmanned aerial vehicles (UAV) survey, electrical resistivity tomography (ERT) survey, ground-penetrating radar (GPR) investigations, single-station seismic ambient noise measurements, and array seismic ambient noise measurements. The integration of the obtained results allowed us to reconstruct a subsoil model of the promontory that includes features related to the local geology of the slope and to the landslide process, as well as to define a conceptual model that describes the main evolution phases of the expansion process. The presence of back-tilted rock blocks with no features of polarization of Rayleigh waves evidenced the different failure mechanism of the rigid UCL plateau at the Sopu promontory with respect to the Selmun promontory, located in the close island of Malta, where the lateral spreading due to the same geological setting tends to produce unstable rock blocks with a toppling mechanism. This result encourages further future observations and analyses of this topic.
Performing Distinction in Big Banana: Culture at the Margins of Visibility
Authors: Teruel Andrea Martinez
Published: February 2024

Central American writers have perceptively engaged with the concept of world literature from their minor positionality. For instance, as implied in the mocking undertone of its title, Roberto Quesada’s Big Banana (2000) deals with being at the edge of the periphery, following a Honduran migrant in the Latin American community in New York. Quesada explores how the protagonist channels his “deseo de mundo”, to use Mariano Siskind’s words, into a strategy of performing distinction to carve out a place for himself in a cosmopolitan society. Compounding “banana republic”—an expression coined by O. Henry, inspired by Honduras—with “The Big Apple”, Big Banana’s title underscores the book’s play with cultural registers and national and worldly identities. The growing scholarship on Central American and U.S. Central American literature has analyzed the novel through the lens of coloniality, the limits of solidarity, the experience of the Central American diaspora, and as “denuncia social”. My article instead traces how cultural productions acquire different valences each time they cross the center–periphery border in the performance of distinction that Big Banana and its protagonist carry out in response to their doubly peripheral position. In other words, this essay is concerned with the novel’s problematic instrumentalization of Western hegemonic culture—both highbrow and commercial popular culture—to make claims of worldliness and carve a space for itself in world literary circuits.
Family in Crisis: Do Halfway Houses Perform Better Than Families with Expressed Emotion toward Patients with Schizophrenia? A Direct Adjusted Comparison
Authors: Ferentinos Panagiotis , Douki Stamatina , Yotsidi Vasiliki , Kourkouni Eleni , Dragoumi Dimitra , Smyrnis Nikolaos , Douzenis Athanasios
Published: February 2024

Expressed emotion (EE) toward patients with schizophrenia is typically reported to be lower in psychiatric halfway houses than in families. This is the first study directly comparing EE between these settings and investigating the pathways mediating EE differences. We included 40 inpatients in halfway houses and 40 outpatients living with their families and recorded 22 psychiatric nurses’ and 56 parents’ EE, respectively, through Five Minutes Speech Samples. Each inpatient was rated by 2–5 nurses and each outpatient by 1–2 parents. As EE ratings had a multilevel structure, generalized linear mixed models were fitted, adjusting for patient-related confounders and caregiver demographics. Mediatory effects were investigated in multilevel structural equation models. Outpatients were younger, less chronic, and better educated, with higher negative symptoms and perceived criticism than inpatients. Nurses were younger and better educated than parents. Before adjustment, EE rates were equally high across settings. After adjusting for patient-related confounders, emotional overinvolvement was significantly higher in parents. However, after also adjusting for caregiver demographics, only criticism was significantly higher in nurses. Patients’ age, negative symptoms, and perceived criticism and caregivers’ age and sex significantly mediated EE group differences. Our findings highlight pathways underlying EE differences between halfway houses and families and underscore the importance of staff and family psychoeducation.
Assessment, Treatment, and Follow-Up of Phlebitis Related to Peripheral Venous Catheterisation: A Delphi Study in Spain
Authors: Torné-Ruiz Alba , Reguant Mercedes , Sanromà-Ortiz Montserrat , Piriz Marta , Roca Judith , García-Expósito Judith
Published: February 2024

Background: Phlebitis related to peripheral venous catheters (PVCs) is a common complication in patients who require these devices and can have important consequences for the patients and the healthcare system. The management and control of the PVC-associated complications is related to nursing competency. The present study aims to determine, at the national level in Spain, the consensus on the assessment, treatment, and follow-up of PVC-related phlebitis and the importance of the actions taken. Method: A three-round Delphi technique was used with clinical care nurses who are experts in the field of in-hospital intravenous treatment in Spain. For this, an online questionnaire was developed with three open-ended questions on the dimensions of phlebitis assessment, treatment, and follow-up. For the statistical analysis of the results, frequencies and percentages were used to determine consensus, and the measures of central tendency (mean, standard deviation, and the coefficient of variation) were used to rank importance. The coefficient of variation was set as acceptable at ≤30%. Results: The final sample was 27 expert nurses. At the conclusion of round 3, actions were ranked according to their importance, with six items included in the PVC-related phlebitis assessment (symptomatology/observation, redness, the Maddox scale, induration, temperature, and pain), two in treatment (catheter removal, pentosan polysulphate sodium ointment + application of cold), and just one in follow-up (general monitoring + temperature control). Conclusions: There is a major disparity in relation to the PVC-related phlebitis assessment, treatment, and follow-up actions. More clinical studies are therefore needed to minimise the complications associated with the use of PVCs, given their impact on the quality of care and patient safety and their economic cost.
Making Use of Averaging Methods in MODELLER for Protein Structure Prediction
Authors: Rosignoli Serena , Lustrino Elisa , Di Silverio Iris , Paiardini Alessandro
Published: February 2024

Recent advances in protein structure prediction, driven by AlphaFold 2 and machine learning, demonstrate proficiency in static structures but encounter challenges in capturing essential dynamic features crucial for understanding biological function. In this context, homology-based modeling emerges as a cost-effective and computationally efficient alternative. The MODELLER (version 10.5, accessed on 30 November 2023) algorithm can be harnessed for this purpose since it computes intermediate models during simulated annealing, enabling the exploration of attainable configurational states and energies while minimizing its objective function. There have been a few attempts to date to improve the models generated by its algorithm, and in particular, there is no literature regarding the implementation of an averaging procedure involving the intermediate models in the MODELLER algorithm. In this study, we examined MODELLER’s output using 225 target-template pairs, extracting the best representatives of intermediate models. Applying an averaging procedure to the selected intermediate structures based on statistical potentials, we aimed to determine: (1) whether averaging improves the quality of structural models during the building phase; (2) if ranking by statistical potentials reliably selects the best models, leading to improved final model quality; (3) whether using a single template versus multiple templates affects the averaging approach; (4) whether the “ensemble” nature of the MODELLER building phase can be harnessed to capture low-energy conformations in holo structures modeling. Our findings indicate that while improvements typically fall short of a few decimal points in the model evaluation metric, a notable fraction of configurations exhibit slightly higher similarity to the native structure than MODELLER’s proposed final model. The averaging-building procedure proves particularly beneficial in (1) regions of low sequence identity between the target and template(s), the most challenging aspect of homology modeling; (2) holo protein conformations generation, an area in which MODELLER and related tools usually fall short of the expected performance.
mRNA Delivery: Challenges and Advances through Polymeric Soft Nanoparticles
Authors: Yousefi Adlsadabad Samaneh , Hanrahan John W. , Kakkar Ashok
Published: February 2024

Single-stranded messenger ribonucleic acid (mRNA) plays a pivotal role in transferring genetic information, and tremendous effort has been devoted over the years to utilize its transcription efficacy in therapeutic interventions for a variety of diseases with high morbidity and mortality. Lipid nanocarriers have been extensively investigated for mRNA delivery and enabled the rapid and successful development of mRNA vaccines against SARS-CoV-2. Some constraints of lipid nanocarriers have encouraged the development of alternative delivery systems, such as polymer-based soft nanoparticles, which offer a modular gene delivery platform. Such macromolecule-based nanocarriers can be synthetically articulated for tailored parameters including mRNA protection, loading efficacy, and targeted release. In this review, we highlight recent advances in the development of polymeric architectures for mRNA delivery, their limitations, and the challenges that still exist, with the aim of expediting further research and the clinical translation of such formulations.
Saturation Transfer Difference NMR and Molecular Docking Interaction Study of Aralkyl-Thiodigalactosides as Potential Inhibitors of the Human-Galectin-3 Protein
Authors: Hőgye Fanni , Farkas László Bence , Balogh Álex Kálmán , Szilágyi László , Alnukari Samar , Bajza István , Borbás Anikó , Fehér Krisztina , Illyés Tünde Zita , Timári István
Published: February 2024

Human Galectin-3 (hGal-3) is a protein that selectively binds to β-galactosides and holds diverse roles in both normal and pathological circumstances. Therefore, targeting hGal-3 has become a vibrant area of research in the pharmaceutical chemistry. As a step towards the development of novel hGal-3 inhibitors, we synthesized and investigated derivatives of thiodigalactoside (TDG) modified with different aromatic substituents. Specifically, we describe a high-yielding synthetic route of thiodigalactoside (TDG); an optimized procedure for the synthesis of the novel 3,3′-di-O-(quinoline-2-yl)methyl)-TDG and three other known, symmetric 3,3′-di-O-TDG derivatives ((naphthalene-2yl)methyl, benzyl, (7-methoxy-2H-1-benzopyran-2-on-4-yl)methyl). In the present study, using competition Saturation Transfer Difference (STD) NMR spectroscopy, we determined the dissociation constant (Kd) of the former three TDG derivatives produced to characterize the strength of the interaction with the target protein (hGal-3). Based on the Kd values determined, the (naphthalen-2-yl)methyl, the (quinolin-2-yl)methyl and the benzyl derivatives bind to hGal-3 94, 30 and 24 times more strongly than TDG. Then, we studied the binding modes of the derivatives in silico by molecular docking calculations. Docking poses similar to the canonical binding modes of well-known hGal-3 inhibitors have been found. However, additional binding forces, cation–π interactions between the arginine residues in the binding pocket of the protein and the aromatic groups of the ligands, have been established as significant features. Our results offer a molecular-level understanding of the varying affinities observed among the synthesized thiodigalactoside derivatives, which can be a key aspect in the future development of more effective ligands of hGal-3.
Polyphenolic Characterization and Anti-Inflammatory Effect of In Vitro Digested Extracts of Echinacea purpurea L. Plant Parts in an Inflammatory Model of Human Colon Cells
Authors: Ávila-Gálvez María Ángeles , Giménez-Bastida Juan Antonio , Karadeniz Bulent , Romero-Reyes Salvador , Espín Juan Carlos , Pelvan Ebru , González-Sarrías Antonio
Published: February 2024

Echinacea purpurea L. (EP) preparations are globally popular herbal supplements known for their medicinal benefits, including anti-inflammatory activities, partly related to their phenolic composition. However, regarding their use for the management of inflammation-related intestinal diseases, the knowledge about the fate of orally ingested constituents throughout the human gastrointestinal tract and the exposition of in vitro digested extracts in relevant inflammatory models are unknown. This study investigated for the first time the impact of in vitro gastrointestinal digestion (INFOGEST) on the phenolic composition and anti-inflammatory properties of EP extracts from flowers (EF), leaves (EL), and roots (ER) on IL-1β-treated human colon-derived CCD-18Co cells. Among the seven hydroxycinnamic acids identified using HPLC-UV-MS/MS, chicoric and caftaric acids showed the highest concentrations in EL, followed by EF and ER, and all extracts exerted significant reductions in IL-6, IL-8, and PGE2 levels. After digestion, despite reducing the bioaccessibility of their phenolics, the anti-inflammatory effects were preserved for digested EL and, to a lesser extent, for EF, but not for digested ER. The lower phenolic content in digested EF and ER could explain these findings. Overall, this study emphasizes the potential of EP in alleviating intestinal inflammatory conditions and related disorders.
High Stretch Associated with Mechanical Ventilation Promotes Piezo1-Mediated Migration of Airway Smooth Muscle Cells
Authors: Luo Mingzhi , Gu Rong , Wang Chunhong , Guo Jia , Zhang Xiangrong , Ni Kai , Liu Lei , Pan Yan , Li Jingjing , Deng Linhong
Published: February 2024

Ventilator-induced lung injury (VILI) during mechanical ventilation (MV) has been attributed to airway remodeling involving increased airway smooth muscle cells (ASMCs), but the underlying mechanism is not fully understood. Thus, we aimed to investigate whether MV-associated high stretch (>10% strain) could modulate mechanosensitive Piezo1 expression and thereby alter cell migration of ASMCs as a potential pathway to increased ASMCs in VILI. C57BL/6 mice and ASMCs were subjected to MV at high tidal volume (VT, 18 mL/kg, 3 h) and high stretch (13% strain, 0.5 Hz, 72 h), respectively. Subsequently, the mice or cells were evaluated for Piezo1 and integrin mRNA expression by immunohistochemical staining and quantitative PCR (qPCR), and cell migration and adhesion by transwell and cell adhesion assays. Cells were either treated or not with Piezo1 siRNA, Piezo1-eGFP, Piezo1 knockin, Y27632, or blebbistatin to regulate Piezo1 mRNA expression or inhibit Rho-associated kinase (ROCK) signaling prior to migration or adhesion assessment. We found that expression of Piezo1 in in situ lung tissue, mRNA expression of Piezo1 and integrin αVβ1 and cell adhesion of ASMCs isolated from mice with MV were all reduced but the cell migration of primary ASMCs (pASMCs) isolated from mice with MV was greatly enhanced. Similarly, cell line mouse ASMCs (mASMCs) cultured in vitro with high stretch showed that mRNA expression of Piezo1 and integrin αVβ1 and cell adhesion were all reduced but cell migration was greatly enhanced. Interestingly, such effects of MV or high stretch on ASMCs could be either induced or abolished/reversed by down/up-regulation of Piezo1 mRNA expression and inhibition of ROCK signaling. High stretch associated with MV appears to be a mechanical modulator of Piezo1 mRNA expression and can, thus, promote cell migration of ASMCs during therapeutic MV. This may be a novel mechanism of detrimental airway remodeling associated with MV, and, therefore, a potential intervention target to treat VILI.
Noise Stress Abrogates Structure-Specific Endonucleases within the Mammalian Inner Ear
Authors: Guthrie O’neil W.
Published: February 2024

Nucleotide excision repair (NER) is a multistep biochemical process that maintains the integrity of the genome. Unlike other mechanisms that maintain genomic integrity, NER is distinguished by two irreversible nucleolytic events that are executed by the xeroderma pigmentosum group G (XPG) and xeroderma pigmentosum group F (XPF) structure-specific endonucleases. Beyond nucleolysis, XPG and XPF regulate the overall efficiency of NER through various protein–protein interactions. The current experiments evaluated whether an environmental stressor could negatively affect the expression of Xpg (Ercc5: excision repair cross-complementing 5) or Xpf (Ercc4: excision repair cross-complementing 4) in the mammalian cochlea. Ubiquitous background noise was used as an environmental stressor. Gene expression levels for Xpg and Xpf were quantified from the cochlear neurosensory epithelium after noise exposure. Further, nonlinear cochlear signal processing was investigated as a functional consequence of changes in endonuclease expression levels. Exposure to stressful background noise abrogated the expression of both Xpg and Xpf, and these effects were associated with pathological nonlinear signal processing from receptor cells within the mammalian inner ear. Given that exposure to environmental sounds (noise, music, etc.) is ubiquitous in daily life, sound-induced limitations to structure-specific endonucleases might represent an overlooked genomic threat.
Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia
Authors: Cruz-Miranda Gabriela Marisol , Olarte-Carrillo Irma , Bárcenas-López Diego Alberto , Martínez-Tovar Adolfo , Ramírez-Bello Julian , Ramos-Peñafiel Christian Omar , García-Laguna Anel Irais , Cerón-Maldonado Rafael , May-Hau Didier , Jiménez-Morales Silvia
Published: February 2024

Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein–protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.
Genome-Wide Characterization and Phylogenetic and Stress Response Expression Analysis of the MADS-Box Gene Family in Litchi (Litchi chinensis Sonn.)
Authors: Yang Jie , Chen Rong , Liu Wei , Xiang Xu , Fan Chao
Published: February 2024

The MADS-box protein is an important transcription factor in plants and plays an important role in regulating the plant abiotic stress response. In this study, a total of 94 MADS-box genes were predicted in the litchi genome, and these genes were widely distributed on all the chromosomes. The LcMADS-box gene family was divided into six subgroups (Mα, Mβ, Mγ, Mδ, MIKC, and UN) based on their phylogenetical relationships with Arabidopsis, and the closely linked subgroups exhibited more similarity in terms of motif distribution and intron/exon numbers. Transcriptome analysis indicated that LcMADS-box gene expression varied in different tissues, which can be divided into universal expression and specific expression. Furthermore, we further validated that LcMADS-box genes can exhibit different responses to various stresses using quantitative real-time PCR (qRT-PCR). Moreover, physicochemical properties, subcellular localization, collinearity, and cis-acting elements were also analyzed. The findings of this study provide valuable insights into the MADS-box gene family in litchi, specifically in relation to stress response. The identification of hormone-related and stress-responsive cis-acting elements in the MADS-box gene promoters suggests their involvement in stress signaling pathways. This study contributes to the understanding of stress tolerance mechanisms in litchi and highlights potential regulatory mechanisms underlying stress responses.
Role of Spexin in White Adipose Tissue Thermogenesis under Basal and Cold-Stimulated Conditions
Authors: Gambaro Sabrina E. , Zubiría María G. , Giordano Alejandra P. , Castro Patricia F. , Garraza Carolina , Harnichar Alejandro E. , Alzamendi Ana , Spinedi Eduardo , Giovambattista Andrés
Published: February 2024

Spexin (SPX) is a novel adipokine that plays an emerging role in metabolic diseases due to its involvement in carbohydrate homeostasis, weight loss, appetite control, and gastrointestinal movement, among others. In obese patients, SPX plasma levels are reduced. Little is known about the relationship between SPX and white adipose tissue (WAT) thermogenesis. Therefore, the aim of the present study was to evaluate the role of SPX in this process. C57BL/6J male mice were treated or not with SPX for ten days. On day 3, mice were randomly divided into two groups: one kept at room temperature and the other kept at cold temperature (4 °C). Caloric intake and body weight were recorded daily. At the end of the protocol, plasma, abdominal (epididymal), subcutaneous (inguinal), and brown AT (EAT, IAT, and BAT, respectively) depots were collected for measurements. We found that SPX treatment reduced Uncoupling protein 1 levels in WAT under both basal and cold conditions. SPX also reduced cox8b and pgc1α mRNA levels and mitochondrial DNA, principally in IAT. SPX did not modulate the number of beige precursors. SPX decreased spx levels in IAT depots and galr2 in WAT depots. No differences were observed in the BAT depots. In conclusion, we showed, for the first time, that SPX treatment in vivo reduced the thermogenic process in subcutaneous and abdominal AT, being more evident under cold stimulation.
Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy
Authors: Agafonova Aleksandra , Cosentino Alessia , Romano Ivana Roberta , Giurdanella Giovanni , D’Angeli Floriana , Giuffrida Rosario , Lo Furno Debora , Anfuso Carmelina Daniela , Mannino Giuliana , Lupo Gabriella
Published: February 2024

The blood–retinal barrier (BRB) is strongly compromised in diabetic retinopathy (DR) due to the detachment of pericytes (PCs) from retinal microvessels, resulting in increased permeability and impairment of the BRB. Western blots, immunofluorescence and ELISA were performed on adipose mesenchymal stem cells (ASCs) and pericyte-like (P)-ASCs by co-cultured human retinal endothelial cells (HRECs) under hyperglycemic conditions (HG), as a model of DR. Our results demonstrated that: (a) platelet-derived growth factor receptor (PDGFR) and its activated form were more highly expressed in monocultured P-ASCs than in ASCs, and this expression increased when co-cultured with HRECs under high glucose conditions (HG); (b) the transcription factor Nrf2 was more expressed in the cytoplasmic fraction of ASCs and in the P-ASC nuclear fraction, under normal glucose and, even more, under HG conditions; (c) cytosolic phospholipase A2 activity and prostaglandin E2 release, stimulated by HG, were significantly reduced in P-ASCs co-cultured with HRECs; (d) HO-1 protein content was significantly higher in HG-P-ASCs/HRECs than P-ASCs/HRECs; and (e) VEGF-A levels in media from HG-co-cultures were reduced in P-ASCs/HRECs with respect to ASCs/HRECs. The data obtained highlighted the potential of autologous differentiated ASCs in future clinical applications based on cell therapy to counteract the damage induced by DR.
Post-Transplant Cyclophosphamide Combined with Brilliant Blue G Reduces Graft-versus-Host Disease without Compromising Graft-versus-Leukaemia Immunity in Humanised Mice
Authors: Cuthbertson Peter , Button Amy , Sligar Chloe , Elhage Amal , Vine Kara , Watson Debbie , Sluyter Ronald
Published: February 2024

Allogeneic haematopoietic stem cell transplantation (HSCT) leads to the establishment of graft-versus-leukaemia (GVL) immunity, but in many cases also results in the development of graft-versus-host disease (GVHD). This study aimed to determine if P2X7 antagonism using Brilliant Blue G (BBG) could improve the beneficial effects of post-transplant cyclophosphamide (PTCy) in a humanised mouse model of GVHD, without comprising GVL immunity. NOD.Cg-Prkdcscid Il2rgtm1Wjl (NSG) mice were injected with human peripheral blood mononuclear cells (PBMCs) (Day 0), then with cyclophosphamide (33 mg/kg) on Days 3 and 4, and with BBG (50 mg/kg) (or saline) on Days 0–10. PTCy with BBG reduced clinical GVHD development like that of PTCy alone. However, histological analysis revealed that the combined treatment reduced liver GVHD to a greater extent than PTCy alone. Flow cytometric analyses revealed that this reduction in liver GVHD by PTCy with BBG corresponded to an increase in human splenic CD39+ Tregs and a decrease in human serum interferon-γ concentrations. In additional experiments, humanised NSG mice, following combined treatment, were injected with human THP-1 acute myeloid leukaemia cells on Day 14. Flow cytometric analyses of liver CD33+ THP-1 cells showed that PTCy with BBG did not mitigate GVL immunity. In summary, PTCy combined with BBG can reduce GVHD without compromising GVL immunity. Future studies investigating P2X7 antagonism in combination with PTCy may lead to the development of novel treatments that more effectively reduce GVHD in allogeneic HSCT patients without promoting leukaemia relapse.