bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative Integration of Dual Quantum Cascade Lasers on Silicon Photonics Platform
Authors: Wang Dongbo , Kannojia Harindra Kumar , Jouy Pierre , Giraud Etienne , Suter Kaspar , Maulini Richard , Gachet David , Hetier Léo , Van Steenberge Geert , Kuyken Bart
Published: August 2024

For the first time, we demonstrate the hybrid integration of dual distributed feedback (DFB) quantum cascade lasers (QCLs) on a silicon photonics platform using an innovative 3D self-aligned flip-chip assembly process. The QCL waveguide geometry was predesigned with alignment fiducials, enabling a sub-micron accuracy during assembly. Laser oscillation was observed at the designed wavelength of 7.2 μm, with a threshold current of 170 mA at room temperature under pulsed mode operation. The optical output power after an on-chip beam combiner reached sub-milliwatt levels under stable continuous wave operation at 15 °C. The specific packaging design miniaturized the entire light source by a factor of 100 compared with traditional free-space dual lasers module. Divergence values of 2.88 mrad along the horizontal axis and 1.84 mrad along the vertical axis were measured after packaging. Promisingly, adhering to i-line lithography and reducing the reliance on high-end flip-chip tools significantly lowers the cost per chip. This approach opens new avenues for QCL integration on silicon photonic chips, with significant implications for portable mid-infrared spectroscopy devices.
Bi-Directional and Operand-Controllable In-Memory Computing for Boolean Logic and Search Operations with Row and Column Directional SRAM (RC-SRAM)
Authors: Xiao Han , Zhao Ruiyong , Liu Yulan , Liu Yuanzhen , Chen Jing
Published: August 2024

The von Neumann architecture is no longer sufficient for handling large-scale data. In-memory computing has emerged as the potent method for breaking through the memory bottleneck. A new 10T SRAM bitcell with row and column control lines called RC-SRAM is proposed in this article. The architecture based on RC-SRAM can achieve bi-directional and operand-controllable logic-in-memory and search operations through different signal configurations, which can comprehensively respond to various occasions and needs. Moreover, we propose threshold-controlled logic gates for sensing, which effectively reduces the circuit area and improves accuracy. We validate the RC-SRAM with a 28 nm CMOS technology, and the results show that the circuits are not only full featured and flexible for customization but also have a significant increase in the working frequency. At VDD = 0.9 V and T = 25 °C, the bi-directional search frequency is up to 775 MHz and 567 MHz, and the speeds for row and column Boolean logic reach 759 MHz and 683 MHz.
Current Strategy for Targeting Metallo-β-Lactamase with Metal-Ion-Binding Inhibitors
Authors: Ortega-Balleza Jessica L. , Vázquez-Jiménez Lenci K. , Ortiz-Pérez Eyra , Avalos-Navarro Guadalupe , Paz-González Alma D. , Lara-Ramírez Edgar E. , Rivera Gildardo
Published: August 2024

Currently, antimicrobial resistance (AMR) is a serious health problem in the world, mainly because of the rapid spread of multidrug-resistant (MDR) bacteria. These include bacteria that produce β-lactamases, which confer resistance to β-lactams, the antibiotics with the most prescriptions in the world. Carbapenems are particularly noteworthy because they are considered the ultimate therapeutic option for MDR bacteria. However, this group of antibiotics can also be hydrolyzed by β-lactamases, including metallo-β-lactamases (MBLs), which have one or two zinc ions (Zn2+) on the active site and are resistant to common inhibitors of serine β-lactamases, such as clavulanic acid, sulbactam, tazobactam, and avibactam. Therefore, the design of inhibitors against MBLs has been directed toward various compounds, with groups such as nitrogen, thiols, and metal-binding carboxylates, or compounds such as bicyclic boronates that mimic hydrolysis intermediates. Other compounds, such as dipicolinic acid and aspergillomarasmin A, have also been shown to inhibit MBLs by chelating Zn2+. In fact, recent inhibitors are based on Zn2+ chelation, which is an important factor in the mechanism of action of most MBL inhibitors. Therefore, in this review, we analyzed the current strategies for the design and mechanism of action of metal-ion-binding inhibitors that combat MDR bacteria.
Enhancing Insight into Photochemical Weathering of Flax and Miscanthus: Exploring Diverse Chemical Compositions and Composite Materials
Authors: El Hage Roland , Carvalho Martins Raíssa , Brendlé Clément , Lafon-Pham Dominique , Sonnier Rodolphe
Published: August 2024

The accelerated weathering of flax and miscanthus fibers possessing distinct chemical compositions was investigated. The chosen fibers included raw, extractive-free (EF) and delignified samples (x3), alone and used as fillers in a stabilized polypropylene blue matrix (PP). Modifications in both color and the chemical composition of the fibers throughout the weathering process under ultraviolet (UV) light were meticulously tracked and analyzed by spectrophotometry and attenuated total reflectance with Fourier-transform infrared spectroscopy (ATR-FTIR). The inherent nature and composition of the selected fibers led to varied color-change tendencies. Raw and EF flax fibers exhibited lightening effects, while raw and EF miscanthus fibers demonstrated darkening effects. Extractives exhibited negligible influence on the color alteration of both flax and miscanthus fibers. This disparity between the fibers correlates with their respective lignin content and type, and the significant formation of carbonyl (C=O) groups in miscanthus. Better stability was noted for delignified flax fibers. A comparative study was achieved by weathering the PP matrix containing these various fibers. Contrary to the weathering observations on individual fibers, it was noted that composites containing raw and EF flax fibers exhibited significant color degradation. The other fiber-containing formulations showed enhanced color stability when compared to the pure PP matrix. The study highlights that the UV stability of composites depends on their thermal history. As confirmed by thermogravimetric analysis (TGA), fiber degradation during extrusion may affect UV stability, a factor that is not apparent when fibers alone are subjected to UV aging.
Modification of Fungicide Treatment Needs and Antioxidant Content as a Result of Real-Time Ozonation of Raspberry Plants
Authors: Matłok Natalia , Piechowiak Tomasz , Szostek Małgorzata , Kuboń Maciej , Neuberger Pavel , Kapusta Ireneusz , Balawejder Maciej
Published: August 2024

Raspberry plants need intensive anti-fungal protection. A solution to this problem could be the application of an ozonation process. For this purpose, a technical solution was proposed and implemented in raspberry plant production. The proposal suggests replacing 25% of standard fungicide treatments with ozonation. It was demonstrated that the use of ozone under the proposed conditions made it possible to maintain stable parameters of chlorophyll content and fluorescence (no significant differences), but the intensity of gas exchange was increased. The greatest differences were observed in the second measurement period (T2), when the plants were in the stage of most active development. Additionally, the content and profile of low-molecular-weight antioxidants and the microbial load were determined in the collected fruits. In periods T2 and T3, the proposed method caused a reduction reaching ~2 log cfu g−1 in the microbial content of raspberry fruits. It was shown that ozone treatment intensified the biosynthesis of low-molecular-weight antioxidants in fruit (increasing the total polyphenol content by more than 20%). The proposed scheme allows a 25% reduction in standard fungicide treatments while maintaining the health of cultivated raspberry plants. The reduction in fungicide use aligns with the EU regulations and produces fruit with better quality.
Castanea sativa Mill. By-Products: Investigation of Potential Anti-Inflammatory Effects in Human Intestinal Epithelial Cells
Authors: Pozzoli Carola , Martinelli Giulia , Fumagalli Marco , Di Lorenzo Chiara , Maranta Nicole , Colombo Luca , Piazza Stefano , Dell’Agli Mario , Sangiovanni Enrico
Published: August 2024

Castanea sativa Mill. (C. sativa) processing and pruning generate several by-products, including leaves, burs, and shells (inner and outer teguments), which are considered an important source of high-value phytochemicals. Ellagitannins from C. sativa leaf extracts have been described to impair H. pylori viability and inflammation in gastric cells. Furthermore, chestnut shells showed an important anti-inflammatory effect in gastric epithelial cells. Dietary polyphenols, including tannins, have been reported to interfere with targets of inflammation, including the nuclear factor κB (NF-κB). A promising role as a further therapeutical target for gut disorders has been recently proposed for the regulatory subunit of hypoxia-inducible factor (HIF-1α), as a potential stabilizer of intestinal barrier integrity. Therefore, the main objective of this work is the chemical characterization of several chestnut by-products (bud, spiny bur, wood, pericarp and episperm), together with the exploitation of their anti-inflammatory properties in intestinal cells, scavenging capacity, and stability following gastrointestinal digestion. The chemical characterization confirmed the presence of bioactive polyphenols in the extracts, including ellagitannins. In CaCo-2 cells stimulated by an IL-1β-IFN-γ cocktail, nearly all chestnut by-products (50 µg/mL) inhibited the release of proinflammatory mediators (CXCL-10, IL-8, MCP-1, ICAM), along with the NF-κB-driven transcription, and induced the HRE-driven transcription. The stability of the most promising extracts, identified through PCA and cluster analysis, was addressed by in vitro gastrointestinal digestion. Despite the significant reduction in total polyphenol index of chestnut bud and wood after gastric and intestinal digestion, the activity of these extracts on both scavenging and anti-inflammatory parameters remained promising. These data contribute to exploit the potential of chestnut by-products as sources of dietary polyphenols with anti-inflammatory properties at the intestinal level. Moreover, this study could represent an important step to encourage the recycling and valorization of chestnut by-products, promoting the circular economy and reducing the environmental impact related to the management of agriculture waste.
Agroprospecting of Biowastes: Globe Artichoke (Cynara scolymus L. Cultivar Tema, Asteraceae) as Potential Source of Bioactive Compounds
Authors: Alves-Silva Jorge M. , Zuzarte Mónica , Salgueiro Lígia , Cocco Emma , Ghiani Valentina , Falconieri Danilo , Maccioni Delia , Maxia Andrea
Published: August 2024

Artichokes (Cynara scolymus L.) are valuable foods, thanks to their health benefits, but they generate significant waste during their production, harvesting, and processing, which poses sustainability issues. This study applied an agroprospecting approach to convert Tema artichoke biowaste (TB) into valuable resources, starting from a global perspective of the production chain to the targeted applications based on chemical and biological analysis. The major TB was identified in the outer bracts of the immature flower heads, which were collected throughout the harvesting season, extracted, and analyzed. The most abundant compounds were phenolic acids including chlorogenic acid and caffeoylquinic derivatives. Among flavonoids, cynaroside was the most abundant compound. Multivariate analysis distinguished batches by collection period, explaining 77.7% of the variance, with most compounds increasing in concentration later in the harvest season. Subsequently, TB extracts were analyzed for their potential in wound healing and anti-aging properties. Fibroblasts were used to assess the effect of selected extracts on cell migration through a scratch wound assay and on cellular senescence induced by etoposide. The results show a significant decrease in senescence-associated β-galactosidase activity, γH2AX nuclear accumulation, and both p53 and p21 protein levels. Overall, this study ascribes relevant anti-skin aging effects to TB, thus increasing its industrial value in cosmeceutical and nutraceutical applications.
The Anti-Melanogenic Effects of Ganodermanontriol from the Medicinal Mushroom Ganoderma lucidum through the Regulation of the CREB and MAPK Signaling Pathways in B16F10 Cells
Authors: Park Che-Hwon , Oh Youn-Lee , Shin Ju-Hyeon , Park Young-Jin
Published: August 2024

Ganoderma lucidum, a member of the Basidiomycetes family, is attracting attention for its medicinal potential due to its biological activity and the presence of numerous bioactive compounds. Although it is known that extracts of this mushroom inhibit melanin production, there are few reports on a single substance associated with this effect. In this study, we identified ganodermanontriol (GT), a novel compound from G. lucidum, that effectively inhibited melanin biosynthesis in B16F10 cells. GT inhibits melanin production by suppressing the expression of cellular tyrosinase proteins and microphthalmia-related transcription factor (MITF). Furthermore, GT affects the phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling molecules, which are involved in melanogenesis in B16F10 cells. Finally, the biosynthesis of GT and other substances by G. lucidum was evaluated using HPLC analysis. Thus, this study revealed the mechanism by which GT in G. lucidum inhibits melanin production in B16F10 cells, and these findings will contribute to promoting the potential use of this mushroom in the future.
ZIF-8-Based Nitrogen and Monoatomic Metal Co-Doped Pyrolytic Porous Carbon for High-Performance Supercapacitor Applications
Authors: Han Xiaobo , Geng Yihao , Wang Jieni , Zhang Shuqin , Wei Chenlin , Cao Leichang , Zhang Shicheng
Published: August 2024

Metal–organic frameworks (MOFs) receive wide attention owing to their high specific surface area, porosity, and structural designability. In this paper, ZC-Ru and ZC-Cu electrodes loaded with monatomic Ru and Cu doped with nitrogen were prepared by pyrolysis, ion impregnation, and carbonization process using ZIF-8 synthesized by static precipitation as a precursor. ZC-Cu has a high specific surface area of 859.78 m2 g−1 and abundant heteroatoms O (10.04%) and N (13.9%), showing the specific capacitance of 222.21 F g−1 at 0.1 A g−1 in three-electrode system, and low equivalent series resistance (Rct: 0.13 Ω), indicating excellent energy storage capacity and electrical conductivity. After 10,000 cycles at 1 A g−1 in 6 M KOH electrolyte, it still has an outstanding capacitance retention of 99.42%. Notably, symmetric supercapacitors ZC-Cu//ZC-Cu achieved the maximum power density and energy density of 485.12 W·kg−1 and 1.61 Wh·kg−1, respectively, positioning ZC-Cu among the forefront of previously known MOF-based electrode materials. This work demonstrates the enormous potential of ZC-Cu in the supercapacitor industry and provides a facile approach to the treatment of transition metal.
Update on Obesity and Cardiovascular Risk: From Pathophysiology to Clinical Management
Authors: Gallo Giovanna , Desideri Giovambattista , Savoia Carmine
Published: August 2024

Obesity is an epidemic worldwide. Overweight and multiple obesity-related mechanisms, including dysmetabolic alterations, contribute to cardiovascular deleterious effects. Hence, overweight and obesity have been independently associated with increased cardiovascular risk, whose assessment is crucial for preserving life quality and reducing mortality, and to address appropriate therapeutic strategies in obese patients. Beyond the standard of care in managing overweight and obesity in adults (i.e., diet and physical exercise), several relevant pharmacotherapies have been approved, and several procedures and device types for weight loss have been recommended. In such a contest, medical weight management remains one option for treating excess weight. Most drugs used for obesity reduce appetite and increase satiety and, secondarily, slow gastric emptying to reduce body weight and, therefore, act also to improve metabolic parameters. In this contest, agonists of the glucagon-like peptide-1 receptor (GLP-1RAs) modulate different metabolic pathways associated with glucose metabolism, energy homeostasis, antioxidation, and inflammation. Moreover, this class of drugs has shown efficacy in improving glycemic control, reducing the incidence of cardiovascular events in type 2 diabetic patients, and reducing body weight independently of the presence of diabetes. Recently, in overweight or obese patients with pre-existing cardiovascular disease but without diabetes, the GLP-1RA semaglutide reduced the incidence of cardiovascular and cerebrovascular events and death from cardiovascular causes. Thus, semaglutide has been approved for secondary prevention in obese people with cardiovascular disease. Nevertheless, whether this class of drugs is equally effective for primary prevention in obese people has to be demonstrated. In this review, we will summarize updates on the pathophysiology of obesity, the effects of obesity on cardiovascular risk, the impact of different obesity phenotypes on cardiovascular diseases, and the novelties in the clinical management of obesity for cardiovascular prevention.
An Evaluation of the Nutritional and Promotional Profile of Commercial Foods for Infants and Toddlers in the United States
Authors: Coyle Daisy H. , Shahid Maria , Parkins Kiana , Hu Monica , Padovan Marina , Dunford Elizabeth K.
Published: August 2024

Despite growing concerns over the increasing popularity and health impact of commercial foods for infants and toddlers, no nutrition or promotional guidelines currently exist for the United States. In 2022, the WHO Regional Office for Europe published a nutrient and promotion profile model (NPPM) to provide guidance and regulation for commercially produced infant and toddler foods. This study assessed the nutritional and promotional profile of infant and toddler foods (6–36 months of age) collected from the top 10 grocery chains in 2023. Products were assessed against the WHO NPPM nutritional and promotional requirements. The type and number of claims across packaging type were also assessed. Of the 651 products examined, 60% failed to meet the nutritional requirements of the NPPM, and 0% met the promotional requirements. Almost 100% of products had at least 1 claim on-pack that was prohibited under the NPPM, with some products displaying up to 11 prohibited claims. Snack-size packages had the lowest compliance with nutrient requirements. These findings highlight that urgent work is needed to improve the nutritional quality of commercially produced infant and toddler foods in the United States. The high use of prohibited claims also suggests the need to regulate the type and number of claims allowed on-pack.
Research on the Anti-Fatigue Effects and Mechanisms of Arecoline in Sleep-Deprived Mice
Authors: Wang Danyang , Sun Yuan , Liu Jiameng , Sun Jing , Fan Bei , Lu Cong , Wang Fengzhong
Published: August 2024

The betel nut is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. Arecoline is an active ingredient from the areca nut. It has many pharmacological effects and can affect the central nervous system. In this study, we found that arecoline can relieve fatigue behavior. Objective: This research aims to estimate the anti-fatigue effects of arecoline and explore its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL/6 mice were randomly assigned to six groups: a control group, an SD-induced fatigue model group, a group that received Rhodiola Rosea capsules (2.5 mg/kg), and three arecoline groups, which were administered at low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on mouse fatigue-related behaviors were assessed by behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. The release levels of the related biochemical markers were measured by enzyme-linked immunosorbent assays (ELISAs). Western blotting was employed to quantify the expression levels of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline obviously decreased both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased the contents of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol in the serum, while it elevated the levels of total testosterone, lactate dehydrogenase, and immunoglobulin G. Furthermore, it significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels showed significant increases, cytokine levels were markedly reduced, and the expressions of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissues were significantly upregulated. Conclusions: This study demonstrates that arecoline has anti-fatigue activity, and the specific mechanisms are associated with elevating glucose and lipid metabolism levels, relieving oxidative stress damage, inhibiting neuroinflammatory response, and regulating neurotransmitter levels and the Keap1/Nrf2/HO-1 signaling pathway. The research provides a new direction for arecoline’s potential in preventing and improving fatigue.
A Fixed Combination of Palmitoylethanolamide and Melatonin (PEATONIDE) for the Management of Pain, Sleep, and Disability in Patients with Fibromyalgia: A Pilot Study
Authors: Terribili Riccardo , Vallifuoco Giulia , Bardelli Marco , Frediani Bruno , Gentileschi Stefano
Published: August 2024

Fibromyalgia is characterized by chronic widespread pain, fatigue, and sleep disturbances. Recent theories attribute fibromyalgia to central sensitization syndromes, suggesting altered nociceptive processing leads to hyperalgesia and allodynia. Standardized effective treatments are currently lacking. Palmitoylethanolamide and melatonin have shown pain-relieving effects in chronic pain conditions, including fibromyalgia, with excellent safety. Our open-label study assessed the impact of a daily combination of 1200 mg of palmitoylethanolamide and 0.2 mg of melatonin on pain, sleep, and quality of life in fibromyalgia patients. Between June 2023 and March 2024, 50 patients (2016 ACR criteria) were treated and evaluated at baseline, 1 month, 3 months, and 4 months (1 month discontinuation). The assessments included VAS for pain, ISI for insomnia, HAQ for health assessments, and a tender points evaluation. The patients, averaging 54.12 years old with a 3:1 female-to-male ratio, showed significant improvements in VAS, ISI, and HAQ scores relative to their own baselines and a reduction in tender points at 1 and 3 months, which was maintained at 4 months. No adverse events were reported. This study is the first to demonstrate the efficacy of a palmitoylethanolamide and melatonin combination as an adjunct therapy in fibromyalgia, highlighting its potential to reduce pain and improve sleep and quality of life.
Isotemporal Substitution Effects of Daily Time Use on Cardiorespiratory Fitness of Children in the OptiChild Study: A Mediation Analysis with Diet Quality
Authors: Wang Youxin , Zhang Pingping , Wang Mingyue , Gong Qinghai , Yu Canqing , Wang Haijun , Hebestreit Antje , Lau Patrick W. C. , Wang Hui , Li Li
Published: August 2024

(1) Background: Although daily time-use is associated with diet quality and cardiorespiratory fitness (CRF) in children, their interdependence remains unexplored. This study first examined the associations between reallocating daily movement time and diet quality and CRF, and second the mediating role of diet quality in the relationship between daily time-use and CRF. (2) Methods: This study included 1131 Chinese children (aged 8 to 10 years; median [interquartile range]: 8.5 [8.3, 8.8]) at baseline (September 2022) and 1268 children at the 9-month follow-up (June 2023) from the OptiChild study. Daily durations of moderate-to-vigorous physical activity (MVPA), sleep, and sedentary behavior (e.g., screen time) were self-reported or proxy-reported by parents. Diet quality was assessed via the Diet Quality Questionnaire (DQQ), which uses a 24 h dietary recall and is categorized according to the Global Dietary Recommendations (GDR) score and Food Group Diversity Score (FGDS). The CRF was measured using VO2max after the 20 m shuttle run test. Longitudinal associations between daily time-use, diet quality, and CRF were calculated using isotemporal substitution models. Mediation analyses were used to determine whether diet quality mediated the associations between daily time-use and CRF. (3) Results: Reallocation of 30 min from screen time to MVPA resulted in significant improvements in the GDR score (β baseline = 0.11, p = 0.024; β follow-up = 0.26, p < 0.001), FGDS (β baseline = 0.11, p = 0.006; β follow-up = 0.19, p < 0.001), and CRF (β baseline = 0.40, p < 0.001; β follow-up = 0.26, p = 0.001). Diet quality partially mediated the associations between MVPA, screen time, and CRF. Substituting 30 min of screen time for MVPA led to diet quality mediating a proportion of the association with CRF (GDR score: 11.4%, FGDS: 6.6%). (4) Conclusions: These findings underscore the importance of optimizing daily time-use of MVPA and screen time and improving diet quality to promote physical fitness in school-aged children.
Plasma, Urinary, Erythrocyte and Platelet Zinc Concentrations in Soccer Players
Authors: Toro-Román Víctor , Siquier-Coll Jesús , Grijota Pérez Fco. Javier , Maynar-Mariño Marcos , Bartolomé-Sánchez Ignacio , Robles-Gil María C.
Published: August 2024

Essential trace minerals are vital for general human health and athletic performance. Zinc (Zn) plays critical roles in several biochemical processes in exercise physiology, especially during intense physical exercise. This research aimed to analyze erythrocyte, platelet, plasma and urine Zn concentrations among men’s and female soccer players over a sports season. A total of 22 male soccer players (20.61 ± 2.66 years; 71.50 ± 5.93 kg) and 24 female soccer players (23.37 ± 3.95 years; 59.58 ± 7.17 kg) participated in this longitudinal quasi-experimental study. Three assessments were carried out over the season: 1st evaluation: first week of training (August); 2nd assessment: middle of the season, between the end of the first and second round (January) and 3rd assessment: last week of training (May/June). In all evaluations extracellular (plasma and urine) and intracellular (erythrocytes and platelets) Zn concentrations were determined, as well as physical fitness and several blood parameters. Inductively coupled plasma mass spectrometry was used to measure Zn concentrations. Plasma and urinary concentrations were higher among male soccer players (p < 0.05) while erythrocyte and platelet Zn concentrations were higher in the female soccer players (p < 0.05). Additionally, variations in urinary and platelet Zn concentrations were observed over the season. The differences could be related to muscle mass, muscle damage or the specific sport’s physical demands.
Healthy Eating beyond Whole Grains—Insight on Associations between Diet Quality and Arterial Stiffness in the Brisighella Heart Study Cohort
Authors: Giovannini Marina , Fogacci Federica , D’Addato Sergio , Grandi Elisa , Borghi Claudio , Cicero Arrigo F. G.
Published: August 2024

Although whole grains have well-recognized protective effects against the development of cardiometabolic diseases, whole grain foods are poorly consumed by the general population. The aim of our study was to establish, at a population level, the vascular impact of a low intake of whole grain foods. From the initial cohort of the Brisighella Heart Study, we identified a population sample of 1503 individuals—including 720 men (47.9%) and 783 women (52.1%)—who overall largely consumed refined grain products. Diet quality was estimated by the Short Healthy Eating Index (sHEI), and women were found to have an eating pattern that was overall healthier than men (44.1 ± 8.5 vs. 36.3 ± 8.1, p < 0.001). The development of an age- and blood pressure (BP)-adjusted multiple linear regression model found that carotid–femoral pulse wave velocity (cfPWV) was significantly predicted by the estimated glomerular filtration rate (eGFR, B = −0.148, 95% Confidence Interval (CI) −0.259–−0.038, p < 0.001), serum uric acid (SUA, B = 0.220, 95%CI 0.095–0.320, p = 0.001) and sHEI (B = −0.231, 95%CI −327–−0.089, p < 0.001) in men, and by eGFR (B = −0.152, 95%CI −0.266–−0.052, p < 0.001), body mass index (BMI, B = 0.174, 95%CI 0.111–0.331, p = 0.002), SUA (B = 0.278, 95%CI 0.158–0.354, p < 0.001) and sHEI (B = −0.218, 95%CI −308–−0.115, p < 0.001) in women. Ultimately, a low sHEI score was a significant predictor of arterial stiffness also in a population cohort with a high consumption of refined grain products.
Dupilumab as Therapeutic Option in Polysensitized Atopic Dermatitis Patients Suffering from Food Allergy
Authors: Sernicola Alvise , Amore Emanuele , Rizzuto Giuseppe , Rallo Alessandra , Greco Maria Elisabetta , Battilotti Chiara , Svara Francesca , Azzella Giulia , Nisticò Steven Paul , Dattola Annunziata , Chello Camilla , Pellacani Giovanni , Grieco Teresa
Published: August 2024

IgE-mediated food allergy is characterized immunologically by a type 1 immune response triggered upon exposure to specific foods and clinically by a broad range of manifestations and variable severity. Our understanding of food allergy within the allergic march of atopic dermatitis (AD) is still incomplete despite the related risk of unpredictable and potentially severe associated reactions such as anaphylactic shock. The aim of this pilot study was to investigate the effects of dupilumab, an IL-4/IL-13 monoclonal antibody approved for AD, on the allergic sensitization profile of patients with AD and type 1 hypersensitivity-related comorbidities, including oral allergy syndrome, anaphylaxis, and gastrointestinal disorders. We conducted an observational pilot study with a longitudinal prospective design, enrolling 20 patients eligible for treatment with dupilumab. Laboratory exams for total serum IgE, specific IgE, and molecular allergen components were performed at baseline and after 16 weeks of therapy. Our results demonstrate a statistically significant decrease in molecular components, specific IgE for trophoallergens, and specific IgE for aeroallergens following treatment with dupilumab. We suggest that modulating type 2 immunity may decrease IgE-mediated responses assessed with laboratory exams and therefore could minimize allergic symptoms in polysensitized patients. Upcoming results of randomized controlled trials investigating dupilumab in food allergy are highly anticipated to confirm its potential effect in the treatment of IgE-mediated food allergies.
The Role of Food Matrices Supplemented with Milk Fat Globule Membrane in the Bioaccessibility of Lipid Components and Adaptation of Cellular Lipid Metabolism of Caco-2 Cells
Authors: Martínez-Sánchez Victoria , Calvo María Visitación , Fontecha Javier , Pérez-Gálvez Antonio
Published: August 2024

This study aimed to evaluate the digestive efficiency of food matrices supplemented with milk fat globule membrane isolated from buttermilk (BM-MFGM), using the INFOGEST in vitro digestion protocol hyphenated with the assessment of the digested material on the lipid profile of the Caco-2 cell culture model. First, we examined lipid profiles in food matrices supplemented with BM-MFGM and their subsequent digestion. The results showed distinct lipid profiles in different food matrices and micellar fractions. The presence of BM-MFGM lipids changed the cellular lipid profiles in Caco-2 cell cultures, with diverging contents in cholesteryl esters, triacylglycerides, and neutral lipids depending on the micellar food matrix factor. Hierarchical clustering analysis revealed patterns in cellular lipid responses to micellar stimuli, while volcano plots highlighted significant changes in cellular lipid profiles post-treatment. Thus, this study underscores the importance of in vitro digestion protocols in guiding food matrix selection for bioactive ingredient supplementation, elucidating intestinal epithelium responses to digested food stimuli.
Both Maternal High-Fat and Post-Weaning High-Carbohydrate Diets Increase Rates of Spontaneous Hepatocellular Carcinoma in Aged-Mouse Offspring
Authors: Holt Daniel , Contu Laura , Wood Alice , Chadwick Hannah , Alborelli Ilaria , Insilla Andrea Cacciato , Crea Francesco , Hawkes Cheryl A.
Published: August 2024

Both maternal obesity and postnatal consumption of obesogenic diets contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). However, there is no consensus as to whether diets that are high in fat or carbohydrates/sugars differentially influence the development of HCC. Moreover, the long-term effects of prenatal HF exposure on HCC and whether this is influenced by postnatal diet has not yet been evaluated. C57BL/6 dams were fed either a low-fat, high-carbohydrate control (C) or low-carbohydrate, high-fat (HF) diet. At weaning, male and female offspring were fed the C or HF diet, generating four diet groups: C/C, C/HF, HF/C and HF/HF. Tissues were collected at 16 months of age and livers were assessed for MASLD and HCC. Glucose regulation and pancreatic morphology were also evaluated. Liver tissues were assessed for markers of glycolysis and fatty acid metabolism and validated using a human HCC bioinformatic database. Both C/HF and HF/HF mice developed obesity, hyperinsulinemia and a greater degree of MASLD than C/C and HF/C offspring. However, despite significant liver and pancreas pathology, C/HF mice had the lowest incidence of HCC while tumour burden was highest in HF/C male offspring. The molecular profile of HCC mouse samples suggested an upregulation of the pentose phosphate pathway and a downregulation of fatty acid synthesis and oxidation, which was largely validated in the human dataset. Both pre-weaning HF diet exposure and post-weaning consumption of a high-carbohydrate diet increased the risk of developing spontaneous HCC in aged mice. However, the influence of pre-weaning HF feeding on HCC development appeared to be stronger in the context of post-weaning obesity. As rates of maternal obesity continue to rise, this has implications for the future incidence of HCC and possible dietary manipulation of offspring carbohydrate intake to counteract this risk.
LDL-Cholesterol-Lowering Effects of a Dietary Supplement Containing Onion and Garlic Extract Used in Healthy Volunteers
Authors: Vezza Teresa , Guillamón Enrique , García-García Jorge , Baños Alberto , Mut-Salud Nuria , García-López Jose David , Gómez-Fernández Germán O. , Rodriguez-Nogales Alba , Gálvez Julio , Fonollá Juristo
Published: August 2024

Hypercholesterolemia plays a pivotal role in the development and progression of cardiovascular diseases, and its prevention seems to be a crucial healthcare strategy to ameliorate these conditions. Subjects with mild hypercholesterolemia are frequently advised against using cholesterol-lowering drugs due to potential side effects, with an emphasis instead on prioritizing dietary adjustments and lifestyle modifications as the primary strategy. In this context, the use of dietary supplements based on medicinal plants may be recommended as a complementary approach to managing elevated cholesterol levels. The aim of this study was to investigate the safety and potential therapeutic effectiveness of a standardized formulation containing extracts from garlic and onions in addressing the health concerns of individuals with slightly elevated cholesterol levels. A controlled, randomized, double-blind, two parallel-group study was conducted over 8 weeks, with clinical visits scheduled at baseline, weeks 2 and 4, as well as at the end of the study. The results revealed significant reductions in both low-density lipoprotein cholesterol and total cholesterol levels among participants who received the extract. Additionally, improvements in blood pressure, as well as in oxidative and inflammatory markers were observed, thus suggesting its potential as a valuable therapeutic intervention for managing mild hypercholesterolemia.
In Silico and In Vivo Studies of β-Sitosterol Nanoparticles as a Potential Therapy for Isoprenaline-Induced Cognitive Impairment in Myocardial Infarction, Targeting Myeloperoxidase
Authors: Tallapalli Partha Saradhi , Reddy Yennam Dastagiri , Yaraguppi Deepak A. , Matangi Surya Prabha , Challa Ranadheer Reddy , Vallamkonda Bhaskar , Ahmad Sheikh F. , Al-Mazroua Haneen A. , Rudrapal Mithun , Dintakurthi Sree Naga Bala Krishna Prasanth , Pasala Praveen Kumar
Published: August 2024

Objective: This study aimed to compare the effects of β-sitosterol nanoparticles (BETNs) and β-sitosterol (BET) on cognitive impairment, oxidative stress, and inflammation in a myocardial infarction (MI) rat model using in silico and in vivo methods. Methods: β-Sitosterol (BET) and myeloperoxidase (MPO) ligand-receptor binding affinities were evaluated using Autodock Vina for docking and Gromacs for dynamics simulations. BET nanoparticles, prepared via solvent evaporation, had their size confirmed by a nanoparticle analyzer. ISO-induced cognitive impairment in rats was assessed through Morris water maze and Cook’s pole climbing tests. Oxidative stress, inflammation, and cardiac injury were evaluated by measuring GSH, SOD, MDA, MPO, CkMB, LDH, lipid profiles, and ECGs. Histopathology of the CA1 hippocampus and myocardial tissue was performed using H&E staining. Results: In silico analyses revealed strong binding affinities between BET and MPO, suggesting BET’s potential anti-inflammatory effect. BETN (119.6 ± 42.6 nm; PDI: 0.809) significantly improved MI-induced cognitive dysfunction in rats (p < 0.001 ***), increased hippocampal GSH (p < 0.01 **) and SOD (p < 0.01 **) levels, and decreased hippocampal MDA (p < 0.05 *) and MPO levels (p < 0.01 **). BETNs also elevated cardiac GSH (p < 0.01 **) and SOD (p < 0.01 **) levels and reduced cardiac MPO (p < 0.01 **), CkMB (p < 0.001 **) and LDH (p < 0.001 **) levels. It restored lipid profiles, normalized ECG patterns, and improved histology in the hippocampal CA1 region and myocardium. Conclusions: Compared with BET treatment, BETNs were more effective in improving cognitive impairment, oxidative damage, and inflammation in MI rats, suggesting its potential in treating cognitive dysfunction and associated pathological changes in MI.
Haloperidol for Pain Management: A Narrative Review
Authors: Roldan Carlos J. , Rowland Jonathan W. , Ye Alice L.
Published: August 2024

The use of haloperidol in pain management has been a topic of interest for several decades. Haloperidol is a widely used antipsychotic medication with unique pharmacologic properties that make it a potential candidate for pain management. However, the efficacy and safety of haloperidol for pain management remain controversial. This narrative review provides a summary of the current literature on the use of haloperidol for pain management, including its pharmacology, clinical effectiveness, adverse effects, and dosing regimens. We performed a comprehensive search of the literature for this review. The most robust clinical data from the past decade suggest that haloperidol has good efficacy in the treatment of pain related to gastroparesis and migraines and has shown promise for opioid use reduction in patients with chronic pain or receiving palliative care. The overall side effect profile is excellent, with zero reported events of QT-related cardiac arrest and minimal reports of sedation and transient extrapyramidal effects such as akathisia. Dosing regimens used were heterogeneous, with most ranging from 1 to 5 mg per dose via intravenous, intramuscular, or oral route. Studies with designs that isolated the effects of haloperidol from combinations of other drugs were extremely limited. Further high-quality prospective studies are needed to determine the ideal role of haloperidol in the routine clinical management of painful conditions.
Comprehensive Analysis of Drug-Induced Parkinson-like Events
Authors: Kikegawa Mami , Sone Hideko , Uesawa Yoshihiro
Published: August 2024

Specific drugs are well known to have the capacity to induce Parkinson-like symptoms. Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggered by various drugs, the mechanisms underlying their diverse symptoms remain largely unclear. To investigate this, we used the Japanese Adverse Drug Event Reporting Database, which is maintained by the Pharmaceuticals and Medical Devices Agency, to analyze the risk factors associated with Parkinson-like events along with the associated drug trends and characteristics. Our findings indicate that similar to Parkinson’s disease, age-related differences affect the onset of these reported events, with older individuals being more susceptible. Hierarchical clustering and principal component analysis revealed that the mechanisms triggering these Parkinson-like events are consistent across reports, suggesting a common underlying cause. However, even with a consistent mechanism, the side effects can vary depending on the site of action. These insights underline the importance of the swift identification of the drugs suspected of causing these events and the implementation of measures to reduce their side effects.
Comparison of the In Vivo Efficacy of Cuban (Raydel®) and Chinese (BOC Science) Policosanol in Alleviating Dyslipidemia and Inflammation via Safeguarding Major Organs and Reproductive Health in Hyperlipidemic Zebrafish: A Twelve-Week Consumption Study
Authors: Cho Kyung-Hyun , Lee Yunki , Lee Sang Hyuk , Kim Ji-Eun , Bahuguna Ashutosh
Published: August 2024

Policosanol is a blend of long-chain aliphatic alcohols (LCAAs) and is well-known for several health-beneficial activities; however, the functionality of policosanol varied substantially based on the composition of LCAAs. In this study, two distinct policosanols, Raydel® (extracted from Cuban sugarcane wax) and BOC Sciences (extracted from Chinese sugarcane wax), were dietarily supplemented (0.1% w/w) for 12 weeks in hyperlipidemic zebrafish to examine their influence on the blood lipid profile and functionality of the liver, kidney, and reproductive organs. The results demonstrated a noteworthy impact of both policosanols on preventing high-cholesterol diet (HCD, 4% w/w)-induced dyslipidemia by decreasing total cholesterol (TC) and triglyceride (TG) levels in the plasma. However, compared to BOC Sciences, the Raydel® policosanol exhibited a significantly (p < 0.05) higher efficacy in reducing HCD-induced TC and TG levels. A substantial effect was observed exclusively with the Raydel® policosanol in mitigating HCD-impaired low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels. Hepatic histology and immunohistochemistry (IHC) analysis revealed the higher efficacy of Raydel® policosanol over BOC Sciences policosanol to prevent HCD-provoked fatty liver changes, cellular senescence, oxidative stress, and interleukin (IL)-6 production. Consistently, a significantly higher effect of Raydel® over BOC Sciences policosanol was observed on the protection of kidney, testis, and ovary morphology hampered by HCD consumption. In addition, Raydel® policosanol exhibited a notably stronger effect (~2-fold, p < 0.05) on the egg-laying ability of the zebrafish compared to policosanol from BOC Sciences. Furthermore, Raydel® policosanol plays a crucial role in improving embryo viability and mitigating developmental defects caused by the intake of an HCD. Conclusively, Raydel® policosanol displayed a substantially higher efficacy over BOC Sciences policosanol to revert HCD-induced dyslipidemia, the functionality of vital organs, and the reproductive health of zebrafish.
Drug-Loaded Bioscaffolds for Osteochondral Regeneration
Authors: Tong Yifan , Yuan Jiaqi , Li Zhenguang , Deng Cuijun , Cheng Yu
Published: August 2024

Osteochondral defect is a complex tissue loss disease caused by arthritis, high-energy trauma, and many other reasons. Due to the unique structural characteristics of osteochondral tissue, the repair process is sophisticated and involves the regeneration of both hyaline cartilage and subchondral bone. However, the current clinical treatments often fall short of achieving the desired outcomes. Tissue engineering bioscaffolds, especially those created via three-dimensional (3D) printing, offer promising solutions for osteochondral defects due to their precisely controllable 3D structures. The microstructure of 3D-printed bioscaffolds provides an excellent physical environment for cell adhesion and proliferation, as well as nutrient transport. Traditional 3D-printed bioscaffolds offer mere physical stimulation, while drug-loaded 3D bioscaffolds accelerate the tissue repair process by synergistically combining drug therapy with physical stimulation. In this review, the physiological characteristics of osteochondral tissue and current treatments of osteochondral defect were reviewed. Subsequently, the latest progress in drug-loaded bioscaffolds was discussed and highlighted in terms of classification, characteristics, and applications. The perspectives of scaffold design, drug control release, and biosafety were also discussed. We hope this article will serve as a valuable reference for the design and development of osteochondral regenerative bioscaffolds and pave the way for the use of drug-loaded bioscaffolds in clinical therapy.