bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Seismic Response of Composite Structures Equipped with Wall Dampers Under Multiple Earthquakes
Authors: Katsimpini Panagiota
Published: December 2024

This study investigates the seismic performance of two-, four-, and six-story composite buildings equipped with viscous wall dampers, focusing on structures with concrete-filled steel tubular (CFST) columns and steel beams. Through nonlinear time history analyses using sequential ground motions, the research evaluates the effectiveness of viscous wall dampers in mitigating seismic demands. Results demonstrate significant reductions in both interstory drift ratios and peak floor accelerations across all building heights when dampers are installed. The study particularly highlights the dampers’ effectiveness in controlling drift demands in lower and middle floors while managing acceleration amplification at upper levels. The findings validate the integration of viscous wall dampers into mid-rise composite structures and underscore the importance of considering sequential ground motions in seismic performance evaluations.
The Application of a Sodium Benzoate Salt-Nucleating Agent in Recycled Polyethylene Terephthalate: Crystallization Behavior and Mechanism
Authors: Wang Meizhen , Lin Fuhua , Zhao Tianjiao , Dong Yapeng , Hao Xinyu , Ning Dingyi , Zhang Yanli , Zhang Kexin , Zhou Dan , Luo Jun , Li Xiangyang , Wang Bo
Published: December 2024

The molecular chains of recycled polyethylene terephthalate (rPET) show breakage during daily use, causing poor crystallization and leading to mechanical properties that, when blended with the nucleating agent, become an effective method of solving this problem. The salt-nucleating agent sodium benzoate (SB), disodium terephthalate (DT), and trisodium 1,3,5benzene tricarboxylic (TBT) were synthesized, and an rPET/nucleating agent blend was prepared. The intrinsic viscosity (η) results showed that the η of the rPET/SB was decreased, which indicated the breakage of the rPET molecular chains. The FTIR results indicated that a chemical reaction occurred between the rPET and Na+ of the SB. Moreover, the Na+ content of the DT and TBT were higher than that of the SB, which increased the opportunity for low-molecular-weight rPET to reattach to the organic carboxylic acid portion of the nucleating agent, thereby increasing the η of the rPET/DT and rPET/TBT. The salt-nucleating agent sodium benzoate greatly improved the crystallization properties of the rPET, resulting in the half-crystallization time decreasing, the crystallization temperature increasing, and the effect of SB being better than that of DT and TBT. This was because the nucleating agent caused chemical nucleation with rPET, and the ionic groups acted as nucleation sites, while the rPET/DT and rPET/TBT, which had high molecular weights, hindered the improvement of the crystallization properties. The mechanical properties prove that the rPET/SB decreased due to the severe degradation of the rPET molecular chains. The mechanical properties of the rPET/DT and rPET/TBT were effectively improved because of the nucleating agent refining the grain size of the rPET and the high molecular weight. But the stacking of multitudinous rPET molecular chains can form a structure resembling physical cross-linking, causing a slight decrease in the mechanical properties of the rPET/TBT compared to the rPET/DT.
Dimer Is Not Double: The Unexpected Behavior of Two-Floor Peptide Nanosponge
Authors: Messina Grazia Maria Lucia , De Zotti Marta , Siano Alvaro S. , Mazzuca Claudia , Marletta Giovanni , Palleschi Antonio
Published: December 2024

Using the framework of an investigation of the stimuli-responsive behavior of peptide assembly on a solid surface, this study on the behavior of a chemisorbed peptide on a gold surface was performed. The studied peptide is a dimeric form of the antimicrobial peptide Trichogin GAIV, which was also modified by substituting the glycine with lysine residues, while the N-terminus octanoyl group was replaced by a lipoic one that was able to bind to the gold surface. In this way, a chemically linked peptide assembly that is pH-responsive was obtained because of the protonation/deprotonation of the sidechains of the Lys residues. Information about the effect of protonation/deprotonation equilibria switching the pH from acid (pH = 3) to basic (pH = 11) conditions was obtained macroscopically by performing Quartz crystal microbalance with dissipation monitoring (QCM-D), Surface Plasmon Resonance (SPR), Nanoplasmonic Sensing (NPS), and FTIR techniques. Using molecular dynamics (MD) simulations, it is possible to explain, at the molecular level, our main experimental results: (1) pH changes induce a squeezing behavior in the system, consisting in thickness and mass variations in the peptide layer, which are mainly due to the pH-driven hydrophilic/hydrophobic character of the lysine residues, and (2) the observed hysteresis is due to small conformational rearrangements from helix to beta sheets occurring mainly on the first half of the peptide, closer to the surface, while the second half remains almost unaffected. The latter result, together with the evidence that the layer thickness is not simply double the assembly of the monomeric analog, indicates that the dimeric peptide does not behave as a double monomer, but assumes very peculiar features.
Understanding the Enzymatic Synthesis of a New Biolubricant: Decane-1,10-diyl bis(2-methylpentanoate)
Authors: Ortega-Requena Salvadora , Máximo Fuensanta , Montiel María Claudia , Gómez María , Murcia María Dolores , Bastida Josefa
Published: December 2024

The value of branched esters comes from the special properties they have in cold environments, which allow them to remain liquid over a wide range of temperatures. These properties make them useful for application in the cosmetic industry or as lubricant additives. This paper presents the studies carried out to ascertain the operational feasibility of the enzymatic esterification of 2-methylpentanoic acid (MPA) with 1,10-decanediol (DD), with the objective of obtaining a novel molecule: decane-1,10-diyl bis(2-methylpentanoate) (DDBMP). The enzymatic reaction is conducted in a thermostated batch reactor, utilizing the commercially available immobilized lipase Lipozyme® 435 in a solvent-free medium. The reaction conversion is determined by an acid number determination and a gas chromatographic analysis. The most optimal result is achieved at a temperature of 80 °C, a biocatalyst concentration of 2.5% (w/w), and a non-stoichiometric substrate relation. A preliminary economic study and the calculation of Green Metrics has established that the operation with a 30% molar excess of acid is the best option to obtain a product with 92.6% purity at a lower cost than the other options and in accordance with the 12 Principles of Green Chemistry. The synthetized diester has a viscosity index of 210, indicating that this new molecule can be used as a biolubricant at extreme temperatures.
Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders
Authors: Bo Tomoki , Fujii Junichi
Published: December 2024

Leucine, isoleucine, and valine are collectively known as branched chain amino acids (BCAAs) and are often discussed in the same physiological and pathological situations. The two consecutive initial reactions of BCAA catabolism are catalyzed by the common enzymes referred to as branched chain aminotransferase (BCAT) and branched chain α-keto acid dehydrogenase (BCKDH). BCAT transfers the amino group of BCAAs to 2-ketoglutarate, which results in corresponding branched chain 2-keto acids (BCKAs) and glutamate. BCKDH performs an oxidative decarboxylation of BCKAs, which produces their coenzyme A-conjugates and NADH. BCAT2 in skeletal muscle dominantly catalyzes the transamination of BCAAs. Low BCAT activity in the liver reduces the metabolization of BCAAs, but the abundant presence of BCKDH promotes the metabolism of muscle-derived BCKAs, which leads to the production of glucose and ketone bodies. While mutations in the genes responsible for BCAA catabolism are involved in rare inherited disorders, an aberrant regulation of their enzymatic activities is associated with major metabolic disorders such as diabetes, cardiovascular disease, and cancer. Therefore, an understanding of the regulatory process of metabolic enzymes, as well as the functions of the BCAAs and their metabolites, make a significant contribution to our health.
Heptamethine Cyanine Dye-Doped Single-Walled Carbon Nanotube Electrodes for Improving Performance of HTL-Free Perovskite Solar Cells
Authors: Cai Man-Ge , Watanabe Arina , Xu Zhenyu , Zhai Yong-Chang , Hidayat Achmad Syarif , Ueoka Naoki , Huda Miftakhul , Higuchi Kimitaka , Kauppinen Esko I. , Funabiki Kazumasa , Matsuo Yutaka
Published: December 2024

Perovskite solar cell (PSC) technology holds great promise with continuously improving power conversion efficiency; however, the use of metal electrodes hinders its commercialization and the development of tandem designs. Although single-walled carbon nanotubes (SWCNTs), as one-dimensional materials, have the potential to replace metal electrodes in PSCs, their poor conductivity still limits their application. In this study, the near-infrared (NIR)-absorbing anionic heptamethine cyanine dye-doped SWCNTs functioned in a dual role as an efficient charge-selective layer and electrode in PSCs. Benefiting from the improvement in conductivities and matched energy level of doped-SWCNT, the dual-role SWCNT electrodes applied to PSCs achieved a better performance than the undoped PSCs with a higher short circuit current (JSC) and fill factor (FF).
Molecular Dynamics Insights into Peptide-Based Tetrodotoxin Delivery Nanostructures
Authors: Song Shenghan , Xia Xinyu , Shorty Temair , Li Tongtong , Stevens Amy O. , Zhao Chao , He Yi
Published: December 2024

Tetrodotoxin (TTX), a potent Site-1 sodium channel blocker (S1SCB), offers highly effective local anesthetic properties with minimal addiction potential. To fully leverage TTX’s capabilities as a local anesthetic, it is crucial to develop a drug delivery system that balances its systemic toxicity with its therapeutic efficacy. Recent studies have shown that peptide mixtures, derived from fragments of Site-1 sodium channel proteins and enhanced with hydrophobic tails (designated MP1 and MP2), can self-assemble into nanostructures that exhibit remarkable sustained-release capabilities for TTX. Despite the profound impact that the addition of a hydrophobic tail has on altering the release behavior of the original peptides, the atomic-level interactions and mechanisms underlying this phenomenon remain poorly understood. In this study, a combination of ColabFold and molecular dynamics (MD) simulations were used to investigate the binding interactions between TTX and the nanostructures formed by MP1 and MP2 at an atomic level. Our findings agree with experimental observations and indicate that the MP1/MP2 nanostructure demonstrates greater stability and higher binding affinity for TTX compared to their non-modified counterparts, P1 and P2. The analysis of the simulations revealed that charged amino acids, specifically aspartic acid (ASP) and glutamic acid (GLU), on the peptides are crucial for strong TTX binding and serve as the primary functional sites. Additionally, the stability of the nanostructure significantly affects TTX binding affinity, elucidating why P1, P2, MP1, and MP2 exhibit different binding capabilities despite containing identical charged residues. The results reported here may provide fundamental information to drive future research and enhance the development of TTX-based drug delivery systems.
A Lifetime of Catalytic Micro-/Nanomotors
Authors: He Tao , Yang Yonghui , Chen Xuebo
Published: December 2024

Microscopic and nanoscopic motors, often referred to as micro-/nanomotors, are autonomous devices capable of converting chemical energy from their surroundings into mechanical motion or forces necessary for propulsion. These devices draw inspiration from natural biomolecular motor proteins, and in recent years, synthetic micro-/nanomotors have attracted significant attention. Among these, catalytic micro-/nanomotors have emerged as a prominent area of research. Despite considerable progress in their design and functionality, several obstacles remain, especially regarding the development of biocompatible materials and fuels, the integration of intelligent control systems, and the translation of these motors into practical applications. Thus, a comprehensive understanding of the current advancements in catalytic micro-/nanomotors is critical. This review aims to provide an in-depth overview of their fabrication techniques, propulsion mechanisms, key influencing factors, control methodologies, and potential applications. Furthermore, we examine their physical and hydrodynamic properties in fluidic environments to optimize propulsion efficiency. Lastly, we evaluate their biosafety and biocompatibility to facilitate their use in biological systems. The review also addresses key challenges and proposes potential solutions to advance their practical deployment.
Improved Mechanical Performances of Hastelloy C276 Composite Coatings Reinforced with SiC by Laser Cladding
Authors: Tang Yuqing , Lu Zheng , Zhang Xuan , Wang Xihuai , Zhao Shengbin , Wang Mingdi
Published: December 2024

Composite coatings reinforced with varying mass fractions of SiC particles were successfully fabricated on 316 stainless steel substrates via laser cladding. The phase compositions, elemental distribution, microstructural characteristics, hardness, wear resistance and corrosion resistance of the composite coatings were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Vickers hardness testing, friction-wear testing and electrochemical methods. The coatings have no obvious pores, cracks or other defects. The phase compositions of the Hastelloy C276 coating includes γ-(Ni, Fe), Ni2C, M6C, M2(C, N) and M23C6. SiC addition resulted in the formation of high-hardness phases, such as Cr3Si and S5C3, with their peak intensity increasing with SiC content. The dendrites extend from the bonding zone towards the top of the coatings, and the crystal direction diffuses from the bottom to each area. Compared with the dendritic crystals formed at the bottom, the microstructure at the top is mostly equiaxed crystals and cellular crystals with smaller volume. When SiC powder particles are present around the crystals, the microstructure of the cladding layer grows acicular crystals containing Si and C. These acicular crystals tend to extend away from the residual SiC powder particles, and the grain size in this region is smaller and more densely distributed. This indicates that both melted and unmelted SiC powder particles can contribute to refining the grain structure of the cladding layer. The optimal SiC addition was determined to be 9 wt%, yielding an average microhardness of 670.1 HV0.5, which is 3.05 times that of the substrate and 1.19 times that of the 0 wt% SiC coating. The wear resistance was significantly enhanced, reflected by a friction coefficient of 0.17 (43.59% of the substrate, 68% of 0 wt%) and a wear rate of 14.32 × 10−6 mm3N−1·m−1 (27.35% of the substrate, 40.74% of 0 wt%). The self-corrosion potential measured at 315 mV, with a self-corrosion current density of 6.884 × 10⁻6 A/cm2, and the electrochemical charge-transfer resistance was approximately 25 times that of the substrate and 1.26 times that of the 0 wt%. In this work, SiC-reinforced Hastelloy-SiC composite coating was studied, which provides a new solution to improve the hardness, wear resistance and corrosion resistance of 316L stainless steel.
Recent Advances in Ruddlesden–Popper Phase-Layered Perovskite Sr2TiO4 Photocatalysts
Authors: Wang Pei , Liao Lijun , Chu Hongqi , Xie Ying , Li Zhenzi , Zhou Wei
Published: December 2024

Sr2TiO4, a prominent member of the Ruddlesden–Popper (RP) perovskite family, has garnered significant interest in photocatalysis, primarily owing to its distinctive two-dimensional (2D) layered structure. In this review, we provide an insightful and concise summary of the intrinsic properties of Sr2TiO4, focusing on the electronic, optical, and structural characteristics that render it a promising candidate for photocatalytic applications. Moreover, we delve into the innovative strategies that have been developed to optimize the structural attributes of Sr2TiO4. These strategies aim to maximize light absorption, improve charge separation, and accelerate the photocatalytic reaction rates. By highlighting these unique approaches, we strive to contribute to a more profound understanding of the material’s potential and stimulate further advancements in developing Sr2TiO4-based photocatalytic systems. The review not only synthesizes the existing knowledge but also offers a perspective in future directions for research and application. As the field of photocatalysis continues to evolve, Sr2TiO4 stands poised to play a pivotal role in the quest for more efficient and sustainable solar energy conversion technology.
Separation of Highly Pure Semiconducting Single-Wall Carbon Nanotubes in Alkane Solvents via Double Liquid-Phase Extraction
Authors: Al Shboul Ahmad , Siaj Mohamed , Claverie Jerome
Published: December 2024

This study delves into the distinctive selective property exhibited by a non-conjugated cholesterol-based polymer, poly(CEM11-b-EHA7), in sorting semiconducting single-walled carbon nanotubes (s-SWCNTs) within isooctane. Comprised of 11 repeating units of cholesteryloxycarbonyl-2-hydroxy methacrylate (CEM) and 7 repeating units of 2-ethylhexyl acrylate (EHA), this non-conjugated polymer demonstrates robust supramolecular interactions across the sp2 surface structure of carbon nanotubes and graphene. When coupled with the Double Liquid-Phase Extraction (DLPE) technology, the polymer effectively segregates s-SWCNTs into the isooctane phase (nonpolar) while excluding metallic SWCNTs (m-SWCNTs) in the water phase (polar). DLPE proves particularly efficient in partitioning larger-diameter s-SWCNTs (0.85–1.0 nm) compared to those dispersed directly in isooctane by poly(CEM11-b-EHA7) using direct liquid-phase exfoliation (LPE) techniques for diameters ranging from 0.75 to 0.95 nm. The DLPE method, bolstered by poly(CEM11-b-EHA7), successfully eliminates impurities from s-SWCNT extraction, including residual metallic catalysts and carbonaceous substances, which constitute up to 20% of raw HiPCO SWCNTs. DLPE emerges as a scalable and straightforward approach for selectively extracting s-SWCNTs in nonpolar, low-boiling-point solvents like alkanes. These dispersions hold promise for fabricating fast-drying s-SWCNT inks, which are ideal for printed and flexible thin-film transistors.
Correction: Chen et al. Aerogels Based on Reduced Graphene Oxide/Cellulose Composites: Preparation and Vapour Sensing Abilities. Nanomaterials 2020, 10, 1729
Authors: Chen Yian , Pötschke Petra , Pionteck Jürgen , Voit Brigitte , Qi Haisong
Published: December 2024

In the original publication [...]
The Impact of Economic Income on BMI Trajectory Groups in Chinese Elderly Individuals: A Population-Based Longitudinal Study
Authors: Yao Yecheng , Guo Qiya , Ding Caicui , Zhou Ying , Song Chao , Zhang Yan , Gong Weiyan , Yuan Fan , Chen Zheng , Yu Tanchun , Wu Xinyue , He Li
Published: December 2024

Objective: The objective of this study is to gain insights into the influence of income on the body mass index (BMI) locus in the elderly population. Methods: The Chinese Longitudinal Healthy Longevity and Happy Family Study (CLHLS-HF) was included at baseline (2008) for participants aged 65 years and older. The total number of participants analyzed in this study was 7555. A population-based trajectory model (GBTM) was used. The economic income level was an independent variable and adjusted for age, gender, ethnicity, education, marriage, and physical activity (Model 1), and the baseline BMI value was added in Model 2, with a quadratic of the income added in Model 3. A sensitivity analysis was adopted. Results: Three BMI trajectory groups were identified using GBTM and were labeled as “overweight”, “normal”, and “obesity”. After adjusting for covariates (Model 1), with the increase in economic income, the risk of the elderly transitioning into the overweight trajectory group and the obesity trajectory group was relatively increased. When the baseline BMI values were adjusted for Model 2, the effect of economic income on the overweight and obesity trajectories was enhanced. A sensitivity analysis was performed, and it was found that the result of the positive impact of economic income on the BMI trajectory group was robust. Conclusions: The higher the income, the greater the risk of Chinese elderly individuals developing the overweight or obesity trajectory. It is suggested that elderly individuals with higher economic income especially need interventions and nutrition education to help them acquire nutrition knowledge for a healthy lifestyle. The positive impact of economic income on the BMI trajectories of the elderly provides further directions for preventing and controlling obesity in the elderly.
The Association of Dining Companionship with Energy and Nutrient Intake Among Community-Dwelling Japanese Older Adults
Authors: Minagawa-Watanabe Yuki , Ukawa Shigekazu , Fukumura Tomoe , Okabayashi Satoe , Ando Masahiko , Wakai Kenji , Tsushita Kazuyo , Tamakoshi Akiko
Published: December 2024

Background: Community-dwelling older adults are at risk of malnutrition due to age-related declines in energy and nutrient intake. While the positive effect of dining companions on energy and nutrient intake has been suggested, evidence remains inconclusive. This study investigated the association between the number of dining companions and energy and nutrient intake, as well as the contribution of specific food groups to higher intake in the presence of dining companions. Methods: This cross-sectional study included 2865 community-dwelling older adults. The number of dining companions was assessed through self-administered questionnaires and categorized into three groups (none, 1, ≥2). Dietary intake was evaluated using a validated food frequency questionnaire, and multivariable regression analyses were conducted to control for potential confounders. Results: Participants dining with two or more companions consumed significantly more energy (β 143.85; 95% CI: 30.05, 257.65; p for trend = 0.01), protein (β 6.32; 95% CI: 1.05, 11.59), fat (β 6.78; 95% CI: 2.44, 11.12; p for trend = 0.002), and carbohydrates (β 17.43; 95% CI: 1.48, 33.37; p for trend = 0.06) compared to those dining alone. They also consumed higher amounts of rice, fats and oils, meat, other vegetables, fruits, and mushrooms. Conclusions: Dining with two or more companions is associated with greater energy and nutrient intake, particularly from energy- and nutrient-dense foods. Encouraging shared meals could serve as a potential approach to support dietary quality and address risks of malnutrition in older adults.
Vitamin D, C-Reactive Protein, and Increased Fall Risk: A Genetic Epidemiological Study
Authors: Sutherland Joshua P. , Zhou Ang , Hyppönen Elina
Published: December 2024

Background: Falls are a major public health concern. Daily vitamin D supplementation is a proposed fall prevention strategy; however, safety concerns have arisen from some clinical trials showing increased fall risk when using higher vitamin D dosing methods. The relationship between vitamin D and falls may be influenced by factors, such as inflammation, which can alter the balance of essential nutrients like vitamin D and retinol, potentially affecting motor function. We use a genetic epidemiological approach to explore the association of inflammation, vitamin D, and fall risk. Methods: We included 307,082 UK Biobank participants and conducted observational and Mendelian randomization (MR) analyses to investigate associations between 25-hydroxyvitamin D [25(OH)D] and fall risk, with analyses including restriction to participants who had fallen and had inflammation as defined by CRP ≥ 5 mg/L. Results: In the observational analysis, CRP was associated with a higher (per 5 mg/L CRP increase OR = 1.06, 95% CI 1.05–1.07) and 25(OH)D with a lower odds of falls. The association between 25(OH)D concentrations and fall risk was non-linear (p < 0.001), reflecting a plateauing of the association at higher concentrations. There was an interaction between 25(OH)D and CRP on their association with the odds of falls (p = 0.009). In participants with CRP ≥ 5 mg/L, the association was U-shaped, and the fall risk was elevated for both 25(OH)D < 25 nmol/L and ≥ 100 nmol/L (p < 0.004). The association between high 25(OH)D and falls was most pronounced for participants with CRP ≥ 20 mg/L (≥ 100 nmol/L vs. 50–74.99 nmol/L: OR = 2.40, 95% CI, 1.50–3.86). Genetically predicted higher 25(OH)D was not associated with fall risk in the overall population, but a suggestive association with fall risk was seen in participants who had fallen and had CRP > 20 mg/L (926 cases; OR = 1.20, 95% CI, 1.00–1.44). Conclusions: Our study suggests that inflammation might modify the vitamin D and fall risk relationship. Both low and high 25(OH)D levels are associated with more falls in individuals with chronic inflammation, with supporting evidence seen in both observational and MR analyses. This may provide insight into the increased fall risk following high-dose vitamin D supplementation in clinical trials, warranting further research.
Hyperhomocysteinemia: Underlying Links to Stroke and Hydrocephalus, with a Focus on Polyphenol-Based Therapeutic Approaches
Authors: Ortiz-Salguero Carmen , Romero-Bernal Marina , González-Díaz Ángela , Doush Elaheh , del Río Carmen , Echevarría Miriam , Montaner Joan
Published: December 2024

Hyperhomocysteinemia (HHcy), characterized by elevated homocysteine (HCys) levels, is associated with increased risks of neurovascular diseases such as stroke or hydrocephalus. HHcy promotes oxidative stress, neuroinflammation, and endothelial dysfunction, disrupting the blood–brain barrier and accelerating neurodegeneration. These processes highlight HCys as both a biomarker and a potential therapeutic target in vascular-related neurological disorders. Current research suggests that polyphenols, known for their antioxidant and anti-inflammatory properties, may reduce HCys levels and offer neuroprotection. Polyphenols have demonstrated effectiveness in modulating oxidative stress and inflammatory pathways triggered by HHcy. These compounds may also upregulate enzymatic functions involved in HCys metabolism, thus reducing neurotoxicity. Furthermore, polyphenol-rich diets, like the Mediterranean diet, have been linked to lower HCys levels and a reduced incidence of neurovascular disorders. This review provides an overview of HHcy’s role in neurovascular pathologies and examines the therapeutic potential of polyphenols in managing HCys levels and preventing HCys-induced neurovascular damage.
Evaluation of the Effects of Mulberry Leaf Extracts Morus alba L. on Cardiovascular, Renal, and Platelet Function in Experimental Arterial Hypertension
Authors: Aghdam Masoud Akbari , Pagán Ana , García-Estañ Joaquín , Atucha Noemí M.
Published: December 2024

Introduction: Numerous epidemiological studies have demonstrated that consuming foods rich in polyphenols and flavonoids can have beneficial effects on various diseases, including arterial hypertension (HTN). Recent research from our laboratory has shown that certain flavonoids exhibit antihypertensive properties in several animal models of HTN. Our objective was to evaluate the effect of Morus alba L. (white mulberry) extracts in an experimental HTN model characterized by nitric oxide (NO) deficiency. Methods: Male Sprague-Dawley rats were divided into four groups: a control group, hypertensive rats treated with an NO synthesis inhibitor (L-NAME) in drinking water for six weeks, L-NAME rats treated with Morus alba L. extract, and L-NAME rats treated simultaneously with captopril. After six weeks of treatment, we measured blood pressure, endothelial vascular function in the aorta, and platelet aggregation function. Results: Morus alba L. extract partially prevented the development of arterial hypertension due to NO deficiency, although it did not completely normalize blood pressure as captopril did. The extract reduced the excessive vasoconstrictor response to phenylephrine in aortic rings and improved vasodilation in response to acetylcholine, with both effects dependent on increased NO production. Morus alba L. extract also reduced the increased platelet aggregation in response to ADP and collagen in hypertensive animals, although it did not fully normalize this function. Conclusions: Morus alba L. extract demonstrates antihypertensive effects, improves vascular reactivity, and reduces platelet aggregation in a model of arterial hypertension. These effects are primarily related to an increase in nitric oxide activity.
Food Related Quality of Life in Children with Chronic Gastrointestinal Disorders: Comparative Study Between Inflammatory Bowel Disease and Celiac Disease—Reports from a Romanian Center
Authors: Matran Roxana Elena , Diaconu Andra-Mihaela , Iordache Andreea Maria , Pacurar Daniela , Becheanu Cristina Adriana
Published: December 2024

Background/Objectives: Chronic gastrointestinal disorders often involve nutritional management strategies. On the one hand, inflammatory bowel disease (IBD) is a condition in which most of the patients experience frequent diet manipulation in order to obtain long term remission. On the other hand, for celiac disease (CelD), diet is the only known treatment strategy so far, requiring a life-long gluten-free diet. We aimed to evaluate the comparative food-related quality-of-life (FR-QoL) in light of these dietary interventions between these two conditions. Methods: This is a cross-sectional study, involving children aged 7–18 years diagnosed with IBD and CelD. Assessment of this aspect was performed using the self-reported FR-QoL 29 questionnaire. For CelD, the questionnaires were modified with “CelD” instead of “IBD”. Results: Fifty-one patients were included, 17 in each subgroup (Crohn’s disease (CD), ulcerative colitis (UC), and Celd). FR-QoL scores were negatively correlated with age at inclusion (Spearman’s ρ = −0.284, p = 0.04) and also with age at diagnosis (Spearman’s ρ = −0.291, p = 0.038). The scores were significantly lower in the CD group (64.1 ± 13.4) compared with CelD patients (78.6 ± 20.3), p = 0.036 and UC, p = 0.294. For the IBD group, the scores were not influenced by disease activity. Furthermore, we identified a negative significant correlation between anthropometric indices and FR-QoL scores. Conclusions: The burden of dietary intervention is highest for the CD patients, regardless of their disease activity when compared with UC and CelD patients, most probably because of the unpredictable course and fast response to dietary changes. Although it requires incessantly vigilant eating behavior, CelD has apparently become more “manageable” in recent years.
The Role of Nutrient Supplements in Female Infertility: An Umbrella Review and Hierarchical Evidence Synthesis
Authors: Pandey Chhiti , Maunder Alison , Liu Jing , Vaddiparthi Vaishnavi , Costello Michael F. , Bahri-Khomami Mahnaz , Mousa Aya , Ee Carolyn
Published: December 2024

Background and Objectives: Nutrient supplements are commonly used to improve fertility outcomes by women with infertility trying to conceive spontaneously or utilising medically assisted reproduction (MAR). However, despite their widespread use and perceived safety, there is a lack of clear guidance on the efficacy and safety of these supplements for female infertility. The aim of this umbrella review was to identify the best available and most recent evidence on the efficacy and safety of nutrient supplements for female infertility to provide evidence-based guidance for clinicians and reproductive couples. Methods: Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on nutrient supplements for female infertility, published from August 2017 to January 2024. The primary outcomes were live birth, and clinical and biochemical pregnancy rates. Secondary outcomes were adverse effects including miscarriage and ectopic or multiple pregnancy. Quality assessment was performed using the A MeaSurement Tool to Assess systematic Reviews Version 2.0 (AMSTAR 2), and the certainty of evidence for outcomes were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, where possible. Results: Four meta-analyses were included. Multiple micronutrients and antioxidants increased live birth rates in women utilising MAR and/or trying to conceive spontaneously compared to placebo, standard or no treatment (odds ratio (OR) 2.59 and 1.81 respectively) with very low certainty evidence. L-carnitine, coQ10, melatonin, myo-inositol, NAC and vitamin D increased clinical pregnancy rates in women with PCOS and/or undergoing MAR compared to placebo, standard or no treatment (odds ratio (OR) 11.14, 2.49, 1.66, relative risk (RR) 1.52, OR 2.15, and 1.49 respectively) with very low certainty evidence. Vitamin D did not increase biochemical pregnancy rates in women utilising MAR with very low certainty evidence. NAC, vitamin D, and pooled antioxidants had no effect on miscarriage rates or multiple pregnancy rates in women trying to conceive spontaneously or utilising MAR, with low to very low certainty evidence. Pooled antioxidants had no effect on ectopic pregnancy rates in women trying to conceive spontaneously or utilising MAR, with low certainty evidence. Conclusions: The available evidence is insufficient to recommend nutrient supplementation to improve female infertility in women trying to conceive naturally and those utilising MAR. However, there is currently no indication that these nutrients pose any risk of significant harm. Registration: PROSPERO (CRD42022365966) 20 October 2022.
Protocol of an Efficacy Study on Nursing Consultation in Weight Management and Metabolic Syndrome Based on the Carbohydrate–Insulin Theory in Individuals with First-Episode Psychosis
Authors: Madaria Lander , Aymerich Claudia , Catalan Ana , Gonzalez-Torres Miguel Angel
Published: December 2024

Background: Individuals with severe mental illness live, on average, up to 30 years less than the general population, with cardiovascular disease being the leading cause of death. Metabolic syndrome (MetS) plays a significant role in this, making it crucial to manage this issue in individuals with psychosis at the onset of the illness. The approach to managing this issue has evolved from a focus on calorie counting to a deeper understanding of hormone function, particularly the role of insulin resistance in MetS. Therefore, incorporating this perspective into mental health nursing consultations with individuals experiencing psychosis is of great interest. Methods: In accordance with the SPIRIT guidelines, an open randomized clinical trial is proposed, involving patients from a first-episode psychosis program. Results: The primary outcome will be significant weight loss (≥5%). Secondary outcomes will include changes in metabolic parameters, psychopathological status, quality of life, and physical activity. Participants will be assigned to two groups: one group will attend a series of six previously manualized nursing consultations, while the other will continue with their usual treatment. Results will be evaluated at six months and one year. Conclusions: This study will determine whether a mental health nursing consultation based on the carbohydrate–insulin model of obesity is effective in reducing weight and the risk of MetS in individuals with early-onset psychosis. This study was retrospectively registered on Clinical Trials—NCT06650943.
Intratumoral Fusobacterium nucleatum in Pancreatic Cancer: Current and Future Perspectives
Authors: D’Antonio Domenica Lucia , Zenoniani Anna , Umme Samia , Piattelli Adriano , Curia Maria Cristina
Published: December 2024

The intratumoral microbiome plays a significant role in many cancers, such as lung, pancreatic, and colorectal cancer. Pancreatic cancer (PC) is one of the most lethal malignancies and is often diagnosed at advanced stages. Fusobacterium nucleatum (Fn), an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in several extra-oral human diseases and, lately, in pancreatic cancer progression and prognosis. It is now recognized as oncobacterium. Fn engages in pancreatic tumorigenesis and metastasis through multifaceted mechanisms, including immune response modulation, virulence factors, control of cell proliferation, intestinal metabolite interactions, DNA damage, and epithelial–mesenchymal transition. Additionally, compelling research suggests that Fn may exert detrimental effects on cancer treatment outcomes. This paper extends the perspective to pancreatic cancer associated with Fn. The central focus is to unravel the oncogenomic changes driven by Fn in colonization, initiation, and promotion of pancreatic cancer development. The presence of Fusobacterium species can be considered a prognostic marker of PC, and it is also correlated to chemoresistance. Furthermore, this review underscores the clinical research significance of Fn as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment. It is thought that given the role of Fn in tumor formation and metastasis processes via its FadA, FapA, Fap2, and RadD, new therapies for tumor treatment targeting Fn will be developed.
Therapeutic Drug Monitoring-Guided Linezolid Therapy for the Treatment of Multiple Staphylococcal Brain Abscesses in a 3-Month-Old Infant
Authors: Cascone Anna , De Luca Maia , Simeoli Raffaele , Goffredo Bianca Maria , Cursi Laura , Tripiciano Costanza , Romani Lorenza , Mercadante Stefania , Di Giuseppe Martina , Calo Carducci Francesca Ippolita , Luglietto Davide , Bernaschi Paola , Lancella Laura
Published: December 2024

Brain abscesses are invasive infections of the central nervous system with a high level of treatment complexity especially in pediatric patients. Here, we describe a 3-month-old infant with multiple brain abscesses caused by methicillin-susceptible Staphylococcus aureus (MSSA). The patient was initially treated with empirical antibiotics (ceftriaxone, metronidazole, vancomycin). Upon MSSA identification, therapy was optimized by switching vancomycin to linezolid to improve tissue penetration. Therapeutic drug monitoring (TDM) was performed to check linezolid levels in the plasma and pus of the abscess, confirming drug penetration into brain tissue. A two-stage surgical drainage approach, consisting of repeated pus aspiration through an intracystic catheter, was then performed to achieve a significant reduction in abscess size. After nine weeks of antibiotic therapy, the patient was discharged in good clinical condition. This case highlights the role of linezolid for the treatment of complicated CNS infections and the importance of a multidisciplinary approach, combining TDM-based antibiotic therapy with timely and eventually repeated surgery, in order to effectively treat brain abscesses.
Hybrid Carbohydrate–Lipid Nanocarriers: In Vitro Efficacy Gene-Rated by Association of UV-Absorbers and Raspberry Polyphenols Rich-Fraction
Authors: Badea Nicoleta , Samayoa Diego , Moroşan Alina , Ott Cristina , Lacatusu Ioana
Published: December 2024

Background/Objectives: The study aims to investigate an improved version of lipid nanocarriers (NLCs) (formulated with functional coconut butter and marula oil) by designing hyaluronic acid (HA) decorated NLC co-loaded with dual UVA (butyl methoxy dibenzoyl methane, BMDBM), UVB absorbers (ethyl-hexyl-salicylate, EHS) and a Raspberry rich polyphenols fraction (RPRF) for development of more natural NLC-based to-pical formulations. Methods: Quality and quantitative attributes of classic- and HA-NLC have been assigned based on particle size, electrokinetic potential, encapsulation efficiency, spectroscopic characteristics, and high-resolution mass spectrometry. To establish the performance profile of antioxidant activity, release of active substances, sun blocking action, and photostability, in vitro studies were conducted. Results: NLC with an average size of ~150 nm and zeta potentials < −39.5 mV showed 80% and 93.1% of encapsulation efficiency for BMDBM and EHS, and up to 83% for natural RPRF. A long-lasting release of absorbers, with a maximum cumulative release of 2.1% BMDBM and 4.6% EHS was detected. NLC-UV Abs-RPRF-HA assured 72.83% radical scavenging activity. The IC50 for HA-NLC-UV Abs-RPRF was 6.25-fold lower than NLC-UV Abs-HA, which reflects the greater free radical scavenging action. The conditioned NLC–UV Abs-RPRF-HA cream was able to provide a sun protection factor value of 52 and UVA-PF value of 81, which underlines an impressive removal of both categories of UVA and UVB radiation. A significant photoprotective upregulation, four-fold for the topical formulation with NLC-UV Abs-RPRF-HA, resulted after a simulated irradiation process. Conclusions: HA decorated-NLC-conditioned creams might provide a useful platform for developing na-tural and sophisticated dermal delivery systems, for influencing skin permeability, and for synergistically imparting antioxidant and photoprotective actions to cosmetic pro-ducts.
Evaluation of Prediction Models for the Capping and Breaking Force of Tablets Using Machine Learning Tools in Wet Granulation Commercial-Scale Pharmaceutical Manufacturing
Authors: Kim Sun Ho , Han Su Hyeon , Seo Dong-Wan , Kang Myung Joo
Published: December 2024

Background/Objectives: This study aimed to establish a predictive model for critical quality attributes (CQAs) related to tablet integrity, including tablet breaking force (TBF), friability, and capping occurrence, using machine learning-based models and nondestructive experimental data. Methods: The machine learning-based models were trained on data to predict the CQAs of metformin HCl (MF)-containing tablets using a commercial-scale wet granulation process, and five models were each compared for regression and classification. We identified eight input variables associated with the process and material parameters that control the tableting outcome using feature importance analysis. Results: Among the models, the Gaussian Process regression model provided the most successful results, with R2 values of 0.959 and 0.949 for TBF and friability, respectively. Capping occurrence was accurately predicted by all models, with the Boosted Trees model achieving a 97.80% accuracy. Feature importance analysis revealed that the compression force and magnesium stearate fraction were the most influential parameters in CQA prediction and are input variables that could be used in CQA prediction. Conclusions: These findings indicate that TBF, friability, and capping occurrence were successfully modeled using machine learning with a large dataset by constructing regression and classification models. Applying these models before tablet manufacturing can enhance product quality during wet granulation scale-up, particularly by preventing capping during the manufacturing process without damaging the tablets.
Pharmacokinetic Evaluation of Neutral Sphinghomyelinase2 (nSMase2) Inhibitor Prodrugs in Mice and Dogs
Authors: Ranjit Arina , Lee Chae Bin , Tenora Lukáš , Mettu Vijaya Saradhi , Pal Arindom , Alt Jesse , Slusher Barbara S. , Rais Rana
Published: December 2024

Background: Extracellular vesicles (EVs) can carry pathological cargo, contributing to disease progression. The enzyme neutral sphingomyelinase 2 (nSMase2) plays a critical role in EV biogenesis, making it a promising therapeutic target. Our lab previously identified a potent and selective inhibitor of nSMase2, named DPTIP (IC50 = 30 nM). Although promising, DPTIP exhibits poor pharmacokinetics (PKs) with a low oral bioavailability (%F < 5), and a short half-life (t1/2 ≤ 0.5 h). To address these limitations, we previously developed DPTIP prodrugs by masking its phenolic hydroxyl group, demonstrating improved plasma exposure in mice. Recognizing that species-specific metabolic differences can influence prodrug PK, we expanded our studies to evaluate selected prodrugs in both mice and dogs. Methods: The scaleup of selected prodrugs was completed and two additional valine- ester based prodrugs were synthesized. Mice were dosed prodrugs via peroral route (10 mg/kg equivalent). For dog studies DPTIP was dosed via intravenous (1 mg/kg) or peroral route (2 mg/kg) and prodrugs were given peroral at a dose 2 mg/kg DPTIP equivalent. Plasma samples were collected at predetermined points and analyzed using developed LC/MS-MS methods. Results: In mice, several of the tested prodrugs showed similar or improved plasma exposures compared to DPTIP. However, in dog studies, the double valine ester prodrug 9, showed significant improvement with an almost two-fold increase in DPTIP plasma exposure (AUC0–t = 1352 vs. 701 pmol·h/mL), enhancing oral bioavailability from 8.9% to 17.3%. Conclusions: These findings identify prodrug 9 as a promising candidate for further evaluation and underscore the critical role of species-specific differences in prodrug PKs.
The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential
Authors: Lee Young-Shin , Kwon Ryuk Jun , Lee Hye Sun , Chung Jae Heun , Kim Yun Seong , Jeong Han-Sol , Park Su-Jung , Lee Seung Yeon , Kim Taehwa , Yoon Seong Hoon
Published: December 2024

Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options. This underscores the growing need for novel therapeutic strategies to complement existing treatments and improve patient outcomes. In recent years, pentacyclic triterpenoids, a group of natural compounds, have emerged as promising candidates for cancer therapy due to their anticancer properties. Pentacyclic triterpenoids, such as lupeol, betulinic acid, betulin, oleanolic acid, ursolic acid, glycyrrhetinic acid, glycyrrhizin, and asiatic acid, have demonstrated the ability to inhibit cell proliferation and angiogenesis, induce apoptosis, suppress metastasis, and modulate inflammatory and immune pathways in NSCLC cell line models. These compounds exert their effects by modulating important signaling pathways such as NF-κB, PI3K/Akt, and MAPK. Furthermore, advances in drug delivery technologies such as nanocarriers and targeted delivery systems have improved the bioavailability and therapeutic efficacy of triterpenoids. However, despite promising preclinical data, rigorous clinical trials are needed to verify their safety and efficacy. This review explores the role of triterpenoids in NSCLC and therapeutic potential in preclinical models, focusing on their molecular mechanisms of action.