bluuebunny/crossref_metadata_2025 huggingface dataset:
Strength–Plasticity Relationship and Intragranular Nanophase Distribution of Hybrid (GNS + SiCnp)/Al Composites Based on Heat Treatment
Authors: Zhang Jiajia , Qian Mingfang , Jia Zhenggang , Zhang Xuexi , Li Aibin , Wang Guisong , Geng Lin
Published: May 2024

The distribution of reinforcements and interfacial bonding state with the metal matrix are crucial factors in achieving excellent comprehensive mechanical properties for aluminum (Al) matrix composites. Normally, after heat treatment, graphene nanosheets (GNSs)/Al composites experience a significant loss of strength. Here, better performance of GNS/Al was explored with a hybrid strategy by introducing 0.9 vol.% silicon carbide nanoparticles (SiCnp) into the composite. Pre-ball milling of Al powders and 0.9 vol.% SiCnp gained Al flakes that provided a large dispersion area for 3.0 vol.% GNS during the shift speed ball milling process, leading to uniformly dispersed GNS for both as-sintered and as-extruded (0.9 vol.% SiCnp + 3.0 vol.% GNS)/Al. High-temperature heat treatment at 600 °C for 60 min was performed on the as-extruded composite, giving rise to intragranular distribution of SiCnp due to recrystallization and grain growth of the Al matrix. Meanwhile, nanoscale Al4C3, which can act as an additional reinforcing nanoparticle, was generated because of an appropriate interfacial reaction between GNS and Al. The intragranular distribution of both nanoparticles improves the Al matrix continuity of composites and plays a key role in ensuring the plasticity of composites. As a result, the work hardening ability of the heat-treated hybrid (0.9 vol.% SiCnp + 3.0 vol.% GNS)/Al composite was well improved, and the tensile elongation increased by 42.7% with little loss of the strength. The present work provides a new strategy in achieving coordination on strength–plasticity of Al matrix composites.
High-Performance Materials Improve the Early Shrinkage, Early Cracking, Strength, Impermeability, and Microstructure of Manufactured Sand Concrete
Authors: Zhang Mingming , Gao Shan , Liu Tong , Guo Shuyu , Zhang Shuotian
Published: May 2024

The poor early shrinkage and cracking performances of manufactured sand concrete, waste powder concrete, and recycled aggregate concrete are the main difficulties in engineering applications. To solve these problems, early shrinkage and cracking, strength, and impermeability tests were performed on high-volume stone powder manufactured sand concrete mixed with fly ash and slag powder (FS), a shrinkage-reducing agent (SRA), polyvinyl alcohol (PVA) fibers, and a superabsorbent polymer (SAP). Furthermore, the microstructures and pore structures of these concretes were revealed using nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM). The results showed that the mixture of FS, SRA, PVA fibers, and SAP could effectively inhibit the shrinkage strain and cracking area of the concrete. The effect of the SAP on reducing the early shrinkage of the concrete is the greatest, and the shrinkage strain can be reduced by 76.49%. The PVA fibers had the most obvious effect on inhibiting the early cracking of the concrete, and the total cracking area was reduced by 66.91%. Significantly, the incorporation of the FS can improve the particle gradation and the pore structure and improve its compactness. The PVA fibers not only provide good carriers for cement-based materials but also enhance the bonding force between the particles inside the concrete, filling the pores inside the concrete, inhibiting the loss of water, and reducing the generation of internal microcracks. The FS and PVA can reduce the shrinkage and cracking risk and improve the strength and impermeability of the concrete. Although the SRA and SAP can reduce the shrinkage and cracking risks, it will lead to a significant decrease in the later strength and impermeability. The main reason is that the SRA leads to an increase in micropores in the matrix and microcracks near the aggregate, which are not conducive to the development of the strength and penetration resistance of the MS. Similarly, the SAP can promote the rapid formation of ettringite (Aft) at an early age and improve the early shrinkage, early cracking, and early strength of the concrete. However, with an increase in age, the residual pores, after SAP dehydration, will cause the deterioration of the concrete pore structure, resulting in the deterioration of the strength and impermeability.
Investigation of the Strain–Stress Field in Nanoscale Multilayer Systems by the Phase Plane Method
Authors: Belous Dmitrii , Badalyan Anna , Khomenko Alexei , Goncharov Alexander
Published: May 2024

This paper presents the results of the study of stress relaxation fields, deformation, and temperature of the system of nanostructured multilayer coatings. In the work, a nonlinear relationship between strain and stress was used to take into account nonlinear effects in the mechanism of nanostructure formation. The paper assumes that a friction surface is provided by the self-organization of shear components: both stress and strain on the one hand, and temperature on the other. The studied objects are described in the adiabatic approximation, taking into account the fact of the evolution of stresses and strains. With the help of phase portraits of the system, the dependence of the deformation processes on the stresses arising in the system without coating and with coating is shown. It is shown that the rate of change of deformation depends on the characteristics of the mechanical impact on the coating and on the amount of stress and deformation. A conclusion is drawn regarding the transition process in the presence of two regions (Hooke and plastic deformation) in the corresponding phase portrait of the strain–stress field of the system. The results of the work can be used to determine the effective parameters of a coating in the analysis of experimental time dependences of stresses.
Detailed Investigation of the Eddy Current and Core Losses in Coaxial Magnetic Gears through a Two-Dimensional Analytical Model
Authors: Nikolarea Nikolina , Tzouganakis Panteleimon , Gakos Vasilios , Papalexis Christos , Tsolakis Antonios , Spitas Vasilios
Published: May 2024

This work introduces a 2D model that calculates power losses in coaxial magnetic gears (CMGs). The eddy current losses of the magnets are computed analytically, whereas the core losses of the ferromagnetic segments are computed using an analytical–finite element hybrid model. The results were within 1.51% and 3.18% of those obtained from an FEA for the eddy current and core losses in the CMG for an indicative inner rotor speed of 2500 rpm. In addition, the significance of the circumferential magnet segmentation is demonstrated in the CMGs. Furthermore, a parametric investigation of the efficiency of the system for different applied external loads is carried out. Finally, a mesh sensitivity analysis is performed, along with the computation of the average power losses throughout one full period, resulting in an at least 80% reduction in computational costs with a negligible effect on accuracy. The developed model could be a valuable tool for the minimization of power losses in CMGs since it combines high accuracy with a low computational cost.
An Improved Method to Compute the Mutual Capacitance between Interdigital Transducers in Radio Frequency Surface Acoustic Wave Filters
Authors: Zou Yali , Yang Xinyu , Luo Ping , Liu Yuhao
Published: May 2024

This paper proposes an improved method to calculate the mutual capacitance between interdigital transducer (IDT) electrodes to enhance the accuracy of the traditional coupling-of-modes (COM) model, which is commonly used to simulate surface acoustic wave (SAW) filters and duplexers. In this method, the boundary element method (BEM) is adopted to obtain the capacitance per unit length in a layered medium, while the partial capacitance (PC) method is used to derive the effective relative permittivity of the multi-layered IDT. Numerical results from commercially available software are provided for comparison with the results calculated using the proposed method. The consistent results verify the validity and accuracy of this method, which also demonstrates significantly faster calculation speed compared to commercially available software. Precise electrical response prediction of a dual-mode SAW (DMS) filter can be achieved by applying this method to the COM model, and this ultra-fast calculation method can also be included in filter design optimization.
Impact of Various Essential Oils on the Development of Pathogens of the Fusarium Genus and on Health and Germination Parameters of Winter Wheat and Maize
Authors: Danielewicz Jakub , Grzanka Monika , Sobiech Łukasz , Jajor Ewa , Horoszkiewicz Joanna , Korbas Marek , Blecharczyk Andrzej , Stuper-Szablewska Kinga , Matysiak Kinga
Published: May 2024

Currently, researchers are looking for ways to replace synthetic pesticides with substances of natural origin. Essential oils are produced by plants, among other things, to protect against pathogens, which is why there is interest in their use as fungicides. This experiment assessed the composition of essential oils from a commercial source, their impact on the development of mycelium of pathogens of the Fusarium genus, and the possibility of using them as a pre-sowing treatment. Grains of winter wheat (Triticum aestivum L.) and corn (Zea mays L.) were inoculated with a suspension of mycelium and spores of fungi of the Fusarium genus and then soaked in solutions containing oils of sage (Salvia officinalis L.), cypress (Cupressus sempervirens L.), cumin (Cuminum cyminum L.), and thyme (Thymus vulgaris L.). The obtained results indicate that thyme essential oil had the strongest effect on limiting the development of Fusarium pathogens and seedling infection, but at the same time it had an adverse effect on the level of germination and seedling development of the tested plants. The remaining essential oils influenced the mentioned parameters to varying degrees. Selected essential oils can be an alternative to synthetic fungicides, but they must be selected appropriately.
Novel 9-Methylanthracene Derivatives as p53 Activators for the Treatment of Glioblastoma Multiforme
Authors: Feng Yuxin , Wang Yingjie , Li Xiaoxue , Sun Ziqiang , Qiang Sihan , Wang Hongbo , Liu Yi
Published: May 2024

Glioblastoma multiforme, a highly aggressive and lethal brain tumor, is a substantial clinical challenge and a focus of increasing concern globally. Hematological toxicity and drug resistance of first-line drugs underscore the necessity for new anti-glioma drug development. Here, 43 anthracenyl skeleton compounds as p53 activator XI-011 analogs were designed, synthesized, and evaluated for their cytotoxic effects. Five compounds (13d, 13e, 14a, 14b, and 14n) exhibited good anti-glioma activity against U87 cells, with IC50 values lower than 2 μM. Notably, 13e showed the best anti-glioma activity, with an IC50 value up to 0.53 μM, providing a promising lead compound for new anti-glioma drug development. Mechanistic analyses showed that 13e suppressed the MDM4 protein expression, upregulated the p53 protein level, and induced cell cycle arrest at G2/M phase and apoptosis based on Western blot and flow cytometry assays.
Opportunities, Challenges, and Scientific Progress in Hemp Crops
Authors: Kaminski Kacper Piotr , Hoeng Julia , Goffman Fernando , Schlage Walter K. , Latino Diogo
Published: May 2024

The resurgence of cannabis (Cannabis sativa L.) has been propelled by changes in the legal framework governing its cultivation and use, increased demand for hemp-derived products, and studies recognizing the industrial and health benefits of hemp. This has led to the creation of novel high-cannabidiol, low-Δ9-tetrahydrocannabinol varieties, enabling hemp crop expansion worldwide. This review elucidates the recent implications for hemp cultivation in Europe, with a focus on the legislative impacts on the cultivation practices, prospective breeding efforts, and dynamic scientific landscape surrounding this crop. We also review the current cultivars’ cannabinoid composition of the European hemp market and its major differences with that of the United States.
Molecular and Therapeutic Roles of Non-Coding RNAs in Oral Cancer—A Review
Authors: Umapathy Vidhya Rekha , Natarajan Prabhu Manickam , Swamikannu Bhuminathan
Published: May 2024

Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs’ potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study.
Differing Within-Household Food Security Statuses Are Associated with Varied Maternal Mental Health Outcomes
Authors: Liebe Rachel A. , Holmes Chanit’a , Misyak Sarah A.
Published: May 2024

Household food insecurity is not necessarily equally experienced by all household members, with mothers often changing their intake first when food resources are limited. The purpose of this study was to understand the association between maternal mental health and intrahousehold differences in food security statuses. A cross-sectional survey was administered to Virginia mothers with low income (August–October 2021), assessing validated measures of food security, mental and physical health and related factors. Participants (n = 570) were grouped according to the food security status of adults and children within the household. Linear regression was used to assess the outcomes of interest by group and controlled for key demographic variables. Mothers in households with any food insecurity reported worse overall mental health and used 3–4 more food coping strategies than households experiencing food security (p < 0.05). Only mothers in households where adults experienced food insecurity reported significantly greater anxiety and depressive symptoms (61.5 and 58.1, respectively) compared to households experiencing food security (55.7 and 52.4, p < 0.001). While any experience of household food insecurity is associated with worse maternal mental health, there were differences by the within-household food security status. Future research should explore screening measures that capture specific household members’ food security to connect households with available resources.
Cholesterol-Lowering Bioactive Foods and Nutraceuticals in Pediatrics: Clinical Evidence of Efficacy and Safety
Authors: Fogacci Federica , ALGhasab Naif Saad , Di Micoli Valentina , Giovannini Marina , Cicero Arrigo Francesco Giuseppe
Published: May 2024

Long-term exposure to even slightly elevated plasma cholesterol levels significantly increases the risk of developing cardiovascular disease. The latest evidence recommends an improvement in plasma lipid levels, even in children who are not affected by severe hypercholesterolemia. The risk–benefit profile of pharmacological treatments in pediatric patients with moderate dyslipidemia is uncertain, and several cholesterol-lowering nutraceuticals have been recently tested. In this context, the available randomized clinical trials are small, short-term and mainly tested different types of fibers, plant sterols/stanols, standardized extracts of red yeast rice, polyunsaturated fatty acids, soy derivatives, and some probiotics. In children with dyslipidemia, nutraceuticals can improve lipid profile in the context of an adequate, well-balanced diet combined with regular physical activity. Of course, they should not be considered an alternative to conventional lipid-lowering drugs when necessary.
The Effect of 14-Day Consumption of Hydrogen-Rich Water Alleviates Fatigue but Does Not Ameliorate Dyspnea in Long-COVID Patients: A Pilot, Single-Blind, and Randomized, Controlled Trial
Authors: Tan Yineng , Xie Yixun , Dong Gengxin , Yin Mingyue , Shang Zhangyuting , Zhou Kaixiang , Bao Dapeng , Zhou Junhong
Published: May 2024

(1) Background: Hydrogen (H2) may be a potential therapeutic agent for managing Long COVID symptoms due to its antioxidant and anti-inflammatory properties. However, more scientific literature is needed to describe the effects of H2 administration on treating symptoms. A study aimed to investigate the impact of hydrogen-rich water (HRW) administration on the fatigue and dyspnea of Long-COVID patients for 14 consecutive days. (2) Methods: In this randomized, single-blind, placebo-controlled study, 55 participants were recruited, and 23 of them were excluded. A total of 32 eligible participants were randomized into a hydrogen-rich water (HRW) group (n = 16) and a placebo water (PW) group (n = 16) in which they were instructed to consume hydrogen-rich water or placebo water for 14 days, respectively. The participants completed the Fatigue Severity Scale (FSS), Six-Minute Walk Test (6MWT), 30 s Chair Stand Test (30s-CST), Modified Medical Research Council Dyspnea Rating Scale (mMRC), Pittsburgh Sleep Quality Index (PSQI), and depression anxiety stress scale (DASS-21) before and after the intervention. A linear mixed-effects model was used to analyze the effects of HRW. Cohen’s d values were used to assess the effect size when significance was observed. The mean change with 95% confidence intervals (95% CI) was also reported. (3) Results: The effects of HRW on lowering FSS scores (p = 0.046, [95% CI = −20.607, −0.198, d = 0.696] and improving total distance in the 6WMT (p < 0.001, [95% CI = 41.972, 61.891], d = 1.010), total time for the 30s-CST (p = 0.002, [95% CI = 1.570, 6.314], d = 1.190), and PSQI scores (p = 0.012, [95% CI = −5.169, 0.742], d = 1.274) compared to PW were of a significantly moderate effect size, while there was no significant difference in mMRC score (p = 0.556) or DASS-21 score (p > 0.143). (4) Conclusions: This study demonstrates that HRW might be an effective strategy for alleviating fatigue and improving cardiorespiratory endurance, musculoskeletal function, and sleep quality. Still, it does not ameliorate dyspnea among Long-COVID patients.
Association between Dietary Patterns during Pregnancy and Children’s Neurodevelopment: A Birth Cohort Study
Authors: Ouyang Jiajun , Cai Wenjin , Wu Penggui , Tong Juan , Gao Guopeng , Yan Shuangqin , Tao Fangbiao , Huang Kun
Published: May 2024

Background: Research studies have showed that maternal diet may influence fetal neurodevelopment, but most studies have only assessed single nutrients or food groups. Objective: To investigate the impact of maternal prenatal dietary patterns during pregnancy on child neurodevelopment. Methods: Study participants were obtained from the China National Birth Cohort. The Ages and Stages Questionnaire, Third Edition, was used to assess children’s neurodevelopment at 36 months old. Maternal antenatal dietary data were collected over three trimesters using food frequency questionnaires. Five distinct maternal dietary patterns throughout pregnancy were identified by principal component analysis, namely protein- and micronutrient-rich dietary patterns, low-iron dietary patterns, pasta as the staple food dietary patterns, iron-rich dietary patterns, tubers, fruits, and baked food dietary patterns. Group-based trajectory modeling was performed for dietary patterns present in all three periods. Multiple linear regression models were used for statistical analysis. Results: Children of mothers who followed a high protein- and micronutrient-rich dietary pattern trajectory during pregnancy presented better neurodevelopment, including higher gross motor and problem-solving scores. Furthermore, it was observed that children born of women with low-iron dietary patterns had poorer neurodevelopment. In detail, children born to mothers with a low-iron dietary pattern during the first trimester had lower problem-solving scores, while to those who were exposed to a low-iron dietary pattern in the second and third trimesters had lower gross motor scores. Additionally, children with mothers who had a low-iron dietary pattern in the third trimester had lower communication scores. Conclusions: A nutrition-balanced protein- and micronutrient-rich dietary pattern and adequate iron dietary pattern for mothers throughout pregnancy may be beneficial to children’s neurodevelopment.
The Accumulative Effect of Multiple Postnatal Risk Factors with the Risk of Being Overweight/Obese in Late Childhood
Authors: Wu Ting , Liao Zijun , Wang Jing , Liu Mengjiao
Published: May 2024

Most past studies focused on the associations of prenatal risk factors with the risks of childhood overweight/obesity. Instead, more postnatal risk factors are modifiable, with less knowledge of their cumulative effects on childhood obesity. We analyzed data of 1869 children in an Australian birth cohort. Key postnatal risk factors included: maternal and paternal overweight/obesity during the child’s infancy, tobacco exposure, low family socioeconomic score, breastfeeding duration < 6 months, early introduction of solid foods, and rapid weight gain during infancy. The risk score was the sum of the number of risk factors. The primary outcome is overweight/obesity in late childhood (11–12 years); secondary outcomes are high-fat mass index (FMI), body fat percentage (BF%), and waist-to-height ratio (WHtR). Poisson regression models were used in the analyses. Children with higher risk scores had higher risks of overweight/obesity (p-for-trends < 0.001). After adjusting covariates, compared with those with 0–1 risk factors, children with 4–6 risk factors had 4.30 (95% confidence interval: 2.98, 6.21) times higher risk of being overweight/obesity; the relative risks for high FMI, BF%, and WHtR were 7.31 (3.97, 13.45), 4.41 (3.00, 6.50), and 6.52 (3.33, 12.74), respectively. Our findings highlighted that multiple postnatal risk factors were associated with increased risks of being overweight/obesity in late childhood.
Bioelectrical Impedance Vector Analysis, Nutritional Ultrasound®, and Handgrip Strength as Innovative Methods for Monitoring Critical Anorexia Nervosa Physical Recovery: A Pilot Study
Authors: Romero-Márquez Jose M. , Novo-Rodríguez María , Novo-Rodríguez Cristina , Siles-Guerrero Víctor , Herrera-Montes Isabel , Navarro-Pelayo Francisco Garzón , López-de-la-Torre-Casares Martín , Muñoz-Garach Araceli
Published: May 2024

Eating disorders (EDs) manifest as persistent disruptions in eating habits or related behaviors, significantly impacting physical health and psychosocial well-being. Nutritional assessment in ED patients is crucial for monitoring treatment efficacy. While dual-energy X-ray absorptiometry (DEXA) remains standard, interest in alternative methods such as bioelectrical impedance vector analysis (BIVA) and Nutritional Ultrasound® (NU) has risen due to their affordability and portability. Additionally, hand dynamometry offers a user-friendly approach to assessing grip strength (HGS), indicative of nutritional status. A prospective study was carried out to evaluate the utility of BIVA, NU®, and HGS in 43 female AN patients. Measurements were taken at baseline and hospital discharge. A total of 41 patients completed the study. After the intervention, numerous BIVA-related parameters such as fat (3.5 ± 2 kg vs. 5.3 ± 2.7 kg, p < 0.001) and free fat mass (33.9 ± 3.8 kg vs. 37.5 ± 4.1 kg, p < 0.001) were partially restored. Similarly, Nutritional Ultrasound® showed promising results in assessing body composition changes such as total abdominal fat tissue (0.5 ± 0.3 cm vs. 0.9 ± 0.3 cm, p < 0.05). In the same way, rectus femoris cross-sectional area values correlated with clinical outcomes such as free fat mass (0.883, p < 0.05) and appendicular muscle mass (0.965, p < 0.001). HGS reached the normality percentile after the intervention (21.6 ± 9.1 kg vs. 25.9 ± 12.3 kg, p < 0.05), demonstrating a significant association between grip strength and body composition parameters such as free fat mass (0.658, p < 0.001) and appendicular muscle mass (0.482, p < 0.001). Incorporating BIVA-, NU®-, and HGS-enhanced nutritional assessment into the treatment of AN patients offers cost-effective, portable, and non-invasive alternatives to DEXA. These techniques offer valuable insights into changes in body composition and nutritional status, which, in turn, facilitate treatment monitoring and contribute to improved patient outcomes.
Unveiling the Multifaceted Capabilities of Endophytic Aspergillus flavus Isolated from Annona squamosa Fruit Peels against Staphylococcus Isolates and HCoV 229E—In Vitro and In Silico Investigations
Authors: Fathallah Noha , Elkady Wafaa M. , Zahran Sara A. , Darwish Khaled M. , Elhady Sameh S. , Elkhawas Yasmin A.
Published: May 2024

Recently, there has been a surge towards searching for primitive treatment strategies to discover novel therapeutic approaches against multi-drug-resistant pathogens. Endophytes are considered unexplored yet perpetual sources of several secondary metabolites with therapeutic significance. This study aims to isolate and identify the endophytic fungi from Annona squamosa L. fruit peels using morphological, microscopical, and transcribed spacer (ITS-rDNA) sequence analysis; extract the fungus’s secondary metabolites by ethyl acetate; investigate the chemical profile using UPLC/MS; and evaluate the potential antibacterial, antibiofilm, and antiviral activities. An endophytic fungus was isolated and identified as Aspergillus flavus L. from the fruit peels. The UPLC/MS revealed seven compounds with various chemical classes. The antimicrobial activity of the fungal ethyl acetate extract (FEA) was investigated against different Gram-positive and Gram-negative standard strains, in addition to resistant clinical isolates using the agar diffusion method. The CPE-inhibition assay was used to identify the potential antiviral activity of the crude fungal extract against low pathogenic human coronavirus (HCoV 229E). Selective Gram-positive antibacterial and antibiofilm activities were evident, demonstrating pronounced efficacy against both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). However, the extract exhibited very weak activity against Gram-negative bacterial strains. The ethyl acetate extract of Aspergillus flavus L exhibited an interesting antiviral activity with a half maximal inhibitory concentration (IC50) value of 27.2 µg/mL against HCoV 229E. Furthermore, in silico virtual molecular docking-coupled dynamics simulation highlighted the promising affinity of the identified metabolite, orienting towards three MRSA biotargets and HCoV 229E main protease as compared to reported reference inhibitors/substrates. Finally, ADME analysis was conducted to evaluate the potential oral bioavailability of the identified metabolites.
Genotoxic and Anti-Genotoxic Potential of Hydrosols from Water–Steam Distillation of Oil-Bearing Roses Rosa centifolia L. and Rosa gallica L. from Bulgaria
Authors: Gateva Svetla , Jovtchev Gabriele , Angelova Tsveta , Gerasimova Tsvetelina , Dobreva Ana , Mileva Milka
Published: May 2024

Rosa centifolia L. and Rosa gallica L. (Rosaceae) are grown as raw materials for valuable essential oils and hydrosols. There are scarce data about the biological activities and the genoprotective potential of the hydrosols of these roses. The aim of the study was to provide information on their cytotoxic/genotoxic activity and anti-cytotoxic/anti-genotoxic capacity against mutagenic N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). The evaluation was performed using classical tests for chromosomal aberrations and micronuclei in the higher plant Hordeum vulgare and human lymphocyte test systems. The experimental schemes included combined hydrosol and mutagen treatment. Both hydrosols (6, 14, 20%) had no cytotoxic effect on barley and showed low genotoxicity in both test systems as the injuries were enhanced to a lesser extent compared to the controls. Lymphocytes were more susceptible than H. vulgare. Under the conditions of combined treatment, it was found that the two hydrosols possessed good anti-cytotoxic and anti-genotoxic potential against MNNG. Both rose products exerted genoprotective potential to a similar extent, decreasing the frequencies of aberrations in chromosomes and micronuclei to a significant degree in both types of cells when non-toxic concentrations of hydrosols were applied before MNNG. This was performed both with and without any inter-treatment time. The observed cytoprotective/genoprotective potential suggests that these hydrosols are promising for further application in phytotherapy and medicine.
Small Molecule Drugs Targeting Viral Polymerases
Authors: Palazzotti Deborah , Sguilla Martina , Manfroni Giuseppe , Cecchetti Violetta , Astolfi Andrea , Barreca Maria Letizia
Published: May 2024

Small molecules that specifically target viral polymerases—crucial enzymes governing viral genome transcription and replication—play a pivotal role in combating viral infections. Presently, approved polymerase inhibitors cover nine human viruses, spanning both DNA and RNA viruses. This review provides a comprehensive analysis of these licensed drugs, encompassing nucleoside/nucleotide inhibitors (NIs), non-nucleoside inhibitors (NNIs), and mutagenic agents. For each compound, we describe the specific targeted virus and related polymerase enzyme, the mechanism of action, and the relevant bioactivity data. This wealth of information serves as a valuable resource for researchers actively engaged in antiviral drug discovery efforts, offering a complete overview of established strategies as well as insights for shaping the development of next-generation antiviral therapeutics.
Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues
Authors: Fedorovskiy Artem G. , Antropov Denis N. , Dome Anton S. , Puchkov Pavel A. , Makarova Daria M. , Konopleva Maria V. , Matveeva Anastasiya M. , Panova Eugenia A. , Shmendel Elena V. , Maslov Mikhail A. , Dmitriev Sergey E. , Stepanov Grigory A. , Markov Oleg V.
Published: May 2024

Over the past decade, mRNA-based therapy has displayed significant promise in a wide range of clinical applications. The most striking example of the leap in the development of mRNA technologies was the mass vaccination against COVID-19 during the pandemic. The emergence of large-scale technology and positive experience of mRNA immunization sparked the development of antiviral and anti-cancer mRNA vaccines as well as therapeutic mRNA agents for genetic and other diseases. To facilitate mRNA delivery, lipid nanoparticles (LNPs) have been successfully employed. However, the diverse use of mRNA therapeutic approaches requires the development of adaptable LNP delivery systems that can control the kinetics of mRNA uptake and expression in target cells. Here, we report effective mRNA delivery into cultured mammalian cells (HEK293T, HeLa, DC2.4) and living mouse muscle tissues by liposomes containing either 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) or the newly applied 1,30-bis(cholest-5-en-3β-yloxycarbonylamino)-9,13,18,22-tetraaza-3,6,25,28-tetraoxatriacontane tetrahydrochloride (2X7) cationic lipids. Using end-point and real-time monitoring of Fluc mRNA expression, we showed that these LNPs exhibited an unusually delayed (of over 10 h in the case of the 2X7-based system) but had highly efficient and prolonged reporter activity in cells. Accordingly, both LNP formulations decorated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) provided efficient luciferase production in mice, peaking on day 3 after intramuscular injection. Notably, the bioluminescence was observed only at the site of injection in caudal thigh muscles, thereby demonstrating local expression of the model gene of interest. The developed mRNA delivery systems hold promise for prophylactic applications, where sustained synthesis of defensive proteins is required, and open doors to new possibilities in mRNA-based therapies.
Integrating Clopidogrel’s First-Pass Effect in a Joint Semi-Physiological Population Pharmacokinetic Model of the Drug and Its Inactive Carboxylic Acid Metabolite
Authors: Pejčić Zorica , Topić Vučenović Valentina , Miljković Branislava , Vučićević Katarina M.
Published: May 2024

Clopidogrel (CLO), a pro-drug for preventing thrombotic events, undergoes rapid absorption and extensive metabolism, with approximately 85–90% converted to an inactive carboxylic acid metabolite (CLO-CA) and the remaining to an active thiol (CLO-TH). Few pharmacokinetic models for the drug and its metabolites exist, with most focusing on CLO-TH. Although CLO-CA is inactive, its predominant (compared to its parent drug and metabolites) presence in plasma underscores the importance of characterizing its formation and pharmacokinetic profile. This study aimed to characterize the process of the absorption of CLO and its conversion to CLO-CA via developing a population pharmacokinetic model. Individual participants’ data from two bioequivalence studies were utilized. Extensive blood samples were collected at predetermined intervals, including 841 concentrations of CLO and 1149 of CLO-CA. A nonlinear, mixed-effects modelling approach using NONMEM® software (v 7.5) was applied. A one-compartment model was chosen for CLO, while a two-compartment proved optimal for CLO-CA. Absorption from the depot compartment was modeled via two transit compartments, incorporating transit rate constants (Ktr). A semi-physiological model explained the first-pass effect of CLO, integrating a liver compartment. The estimated mean transit times (MTTs) for the studies were 0.470 and 0.410 h, respectively. The relative bioavailability for each study’s generic medicine compared to the reference were 1.08 and 0.960, respectively. Based on the estimated parameters, the fractions metabolized to inactive metabolites (FiaM_st1 and FiaM_st2) were determined to be 87.27% and 86.87% for the two studies, respectively. The appropriateness of the final model was confirmed. Our model offers a robust framework for elucidating the pharmacokinetic profiles of CLO and CLO-CA.
Comparative Study of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy and the Loop Electrosurgical Excision Procedure for the Treatment of Cervical High-Grade Squamous Intraepithelial Lesions
Authors: Wang Xiaoyun , Xu Xiaoming , Ma Yaxi , Tang Yixin , Huang Zheng
Published: May 2024

The loop electrosurgical excision procedure (LEEP) is a common treatment for cervical intraepithelial neoplasia (CIN). Photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) is a non-invasive modality that has been used for treating precancerous diseases and HPV infections. This comparative study evaluated the efficacy and safety of ALA PDT and the LEEP in the treatment of cervical high-grade squamous intraepithelial lesions (HSILs). Patient records were reviewed and HSIL patients with HPV infections (24–51 years old) who underwent PDT or LEEP treatment were selected. Efficacy was analyzed blindly based on HPV-DNA, cytology, and colposcopy-directed biopsy obtained at 6 months after treatment. Treatment-related discomfort and side effects were also analyzed. Cure rates of 88.1% and 70.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. HPV-negative conversion rates of 81.0% and 62.0% were achieved for the PDT group and LEEP group (p < 0.05), respectively. The overall lesion remission rate of the PDT group was 19% higher than that of the LEEP group. The incidence of side effects was much lower in the PDT group. These results show that ALA PDT is a feasible non-invasive treatment for cervical HSIL.
Formulation of Ascorbic Acid and Betaine-based Therapeutic Deep Eutectic System for Enhanced Transdermal Delivery of Ascorbic Acid
Authors: Song Ji-Eun , Jun Seung-Hyun , Ryoo Joo-Yeon , Kang Nae-Gyu
Published: May 2024

L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems.
Polymer Matrix and Manufacturing Methods in Solid Dispersion System for Enhancing Andrographolide Solubility and Absorption: A Systematic Review
Authors: Tipduangta Pratchaya , Chansakaow Sunee , Tansakul Pimpimon , Meungjai Rungarun , Dilokthornsakul Piyameth
Published: May 2024

Background: Andrographolide (ADG) has poor aqueous solubility and low bioavailability. This study systematically reviews the use of solid dispersion (SD) techniques to enhance the solubility and absorption of ADG, with a focus on the methods and polymers utilized. Methodology: We searched electronic databases including PubMed, Web of Science, Scopus®, Embase and ScienceDirect Elsevier® up to November 2023 for studies on the solubility or absorption of ADG in SD formulations. Two reviewers independently reviewed the retrieved articles and extracted data using a standardized form and synthesized the data qualitatively. Results: SD significantly improved ADG solubility with up to a 4.7-fold increase and resulted in a decrease in 50% release time (T1/2) to less than 5 min. SD could also improve ADG absorption, as evidenced by higher Cmax and AUC and reduced Tmax. Notably, Soluplus-based SDs showed marked solubility and absorption enhancements. Among the five SD techniques (rotary evaporation, spray drying, hot-melt extrusion, freeze drying and vacuum drying) examined, spray drying emerged as the most effective, enabling a one-step process without the need for post-milling. Conclusions: SD techniques, particularly using Soluplus and spray drying, effectively enhance the solubility and absorption of ADG. This insight is vital for the future development of ADG-SD matrices.
Development of a Web Application for Simulating Plasma Drug Concentrations in Patients with Zolpidem Intoxication
Authors: Cha Hwa Jun , Han Sungpil , Pak Kwan Cheol , Kim Hyungsub
Published: May 2024

Zolpidem is a widely prescribed hypnotic Z-drug used to treat short-term insomnia. However, a growing number of individuals intentionally overdose on these drugs. This study aimed to develop a predictive tool for physicians to assess patients with zolpidem overdose. A population pharmacokinetic (PK) model was established using digitized data obtained from twenty-three healthy volunteers after a single oral administration of zolpidem. Based on the final PK model, a web application was developed using open-source R packages such as rxode2, nonmem2rx, and shiny. The final model was a one-compartment model with first-order absorption and elimination with PK parameters, including clearance (CL, 16.9 L/h), absorption rate constant (Ka, 5.41 h−1), volume of distribution (Vd, 61.7 L), and lag time (ALAG, 0.394 h). Using the established population PK model in the current study, we developed a web application that enables users to simulate plasma zolpidem concentrations and visualize their profiles. This user-friendly web application may provide essential clinical information to physicians, ultimately helping in the management of patients with zolpidem intoxication.
The Necessity and Goodness of Animals in Sijistānī’s Kashf Al-Maḥjūb
Authors: Adamson Peter , Amin Beidokhti Hanif
Published: May 2024

The Neoplatonic notion of “emanation” implies a required progression through hierarchical stages, originating from the highest principle (the One or God) and cascading down through a series of principles. While this process is deemed necessary, it is also inherently good, even “choiceworthy”, aligning with the identification of the first principle with the Good. Plotinus, a prominent Neoplatonist, emphasizes the beauty and goodness of the sensible world, governed by divine providence. This perspective, transmitted through Arabic adaptations of Plotinus, influences Islamic philosophers too. This paper delves into the thought of the Ismāʿīlī philosopher Abū Yaʿqūb al-Sijistānī (d. after. 349/971), exploring the interplay of necessity and goodness in his cosmology, with a focus on non-human animals. Sijistānī’s Persian Uncovering the Veiled provides a unique perspective on animals, presenting them as both necessary unfoldings of the universal intellect and inherently good beings with intrinsic value. The paper concludes with an appendix featuring an improved edition and English translation of relevant passages.
Three-Dimensional Bioprinting of GelMA Hydrogels with Culture Medium: Balancing Printability, Rheology and Cell Viability for Tissue Regeneration
Authors: Mendoza-Cerezo Laura , Rodríguez-Rego Jesús M. , Macías-García Antonio , Callejas-Marín Antuca , Sánchez-Guardado Luís , Marcos-Romero Alfonso C.
Published: May 2024

Three-dimensional extrusion bioprinting technology aims to become a fundamental tool for tissue regeneration using cell-loaded hydrogels. These biomaterials must have highly specific mechanical and biological properties that allow them to generate biosimilar structures by successive layering of material while maintaining cell viability. The rheological properties of hydrogels used as bioinks are critical to their printability. Correct printability of hydrogels allows the replication of biomimetic structures, which are of great use in medicine, tissue engineering and other fields of study that require the three-dimensional replication of different tissues. When bioprinting cell-loaded hydrogels, a small amount of culture medium can be added to ensure adequate survival, which can modify the rheological properties of the hydrogels. GelMA is a hydrogel used in bioprinting, with very interesting properties and rheological parameters that have been studied and defined for its basic formulation. However, the changes that occur in its rheological parameters and therefore in its printability, when it is mixed with the culture medium necessary to house the cells inside, are unknown. Therefore, in this work, a comparative study of GelMA 100% and GelMA in the proportions 3:1 (GelMA 75%) and 1:1 (GelMA 50%) with culture medium was carried out to determine the printability of the gel (using a device of our own invention), its main rheological parameters and its toxicity after the addition of the medium and to observe whether significant differences in cell viability occur. This raises the possibility of its use in regenerative medicine using a 3D extrusion bioprinter.
Clay Tailings Flocculated in Seawater and Industrial Water: Analysis of Aggregates, Sedimentation, and Supernatant Quality
Authors: Leiva Williams H. , Toro Norman , Robles Pedro , Quezada Gonzalo R. , Salazar Iván , Jeldres Ricardo
Published: May 2024

High-molecular-weight anionic polyacrylamide was used to analyze the effect of kaolin on the structure of particle aggregates formed in freshwater and seawater. Batch flocculation experiments were performed to determine the size of the flocculated aggregates over time by using focused beam reflectance measurements. Sedimentation tests were performed to analyze the settling rate of the solid–liquid interface and the turbidity of the supernatant. Subsequently, a model that relates the hindered settling rate to the aggregate size was used to determine the mass fractal dimension (Df). Flocculation kinetics revealed that greater amounts of kaolin generated larger aggregates because of its lamellar morphology. The maximum size was between 10 and 20 s of flocculation under all conditions. However, the presence of kaolin reduced the settling rate. The fractal dimension decreased with the increase in the kaolin content, resulting in the formation of irregular and porous aggregates. By contrast, factors such as the flocculation time, water quality, and quartz size had limited influences on the fractal dimension. Seawater produced a clearer supernatant because of its higher ionic strength and precoagulation of particles. Notably, the harmful effect of clays in seawater was reduced.
Investigating the Role of Municipal Waste Treatment within the European Union through a Novel Created Common Sustainability Point System
Authors: Tsimnadis Konstantinos , Kyriakopoulos Grigorios L.
Published: May 2024

Over the last several decades, the European Union (EU) has championed recycling and sustainable waste management through Directives 2008/98/EC and 2018/851, shaping practices across its member states. Currently, 30% of the EU’s municipal waste is recycled, 19% composted, 23% incinerated, and 23% landfilled. However, regional variations exist within the EU, with Greece and other Mediterranean/Balkan nations favoring landfilling, while Germany and other Western/Central EU nations prioritize recycling and composting, and Nordic countries lean toward incineration. To address these differences, a new sustainability point system was created in order to evaluate and compare all different municipal waste management strategies of EU members. Notably, countries like Germany, the Netherlands, and Sweden score the highest due to low municipal waste generation, high recycling rates (>35%), minimal landfilling (<1%), and significant incineration. In contrast, Cyprus, Malta, and Greece score lower due to landfill reliance and lower recycling rates. Therefore, this study introduces a novel sustainability point system to mitigate disparities, highlighting the need for targeted interventions and policy initiatives at the national and EU levels. By leveraging these insights, policymakers can allocate resources effectively, foster collaboration, and motivate citizens to achieve common environmental goals as well as the Sustainable Development Goals (SDGs).
Grounding Intelligibility, Safeguarding Mystery: A Neoclassical Reading of Ernan McMullin’s Legacy
Authors: Barzaghi Amerigo
Published: May 2024

This paper suggests a “neoclassical” reading of Ernan McMullin’s thought on science and theology. McMullin’s Augustinian convictions on God and the God–world relation coincide with those of some prominent scholars from two renowned schools of neo-scholastic philosophy of the twentieth century in Louvain and Milan. The school of Milan, thanks to the work of some disciples of its leading figure, Amato Masnovo, developed a neoclassical version of neo-scholasticism, articulating a fundamental theory of knowledge, as well as an essential, rigorous path to God. We recall the main tenets of a neoclassical path to God, and we interpret this path as a possible contribution to the science–theology dialogue, in line with McMullin’s Augustinism. A neoclassical approach to science and theology, with its rediscovery and reactualization of some ideas of classic philosophy in an interdisciplinary context, grounds the intelligibility of the universe and safeguards its mystery.