Search Results (420)

Background: The first 1000 days of life, from conception to 2 years of age, represent a critical window during which nutrition can exert long-lasting effects on neurodevelopment, immune maturation, and susceptibility to prematurity-related morbidity. Docosahexaenoic acid (DHA) is a key structural n-3 long-chain polyunsaturated fatty acid of the brain and retina, characterized by rapid fetal accretion during the third trimester. Methods: We conducted a narrative review of studies published from March 2015 up to December 2025, including randomized controlled trials, follow-up studies, and systematic reviews/meta-analyses about DHA supplementation during pregnancy, lactation, infancy and early childhood, and its role on development. Results: Across the first 1000 days, DHA supplementation improves biochemical DHA status, particularly in populations with low baseline levels (moderate to high level of evidence), while clinical outcomes remain heterogeneous. During pregnancy, some benefits in specific cognitive and behavioral domains have been demonstrated, whereas effects on global cognition and long-term behavior are frequently null (moderate evidence). Visual outcomes appear favorable, with improvements in visual acuity (moderate evidence). In preterm infants, enteral DHA—often combined with arachidonic acid (ARA)—is feasible and well tolerated. DHA may reduce inflammatory markers and necrotizing enterocolitis risk when in equilibrium with ARA (low to moderate evidence), while no evidence supports the link between DHA and reduced risk of bronchopulmonary dysplasia and retinopathy of prematurity (moderate evidence). Neurodevelopmental outcomes are mixed: neuroimaging studies suggest enhanced white matter maturation with DHA + ARA, whereas most trials show no clear benefit regarding standardized developmental scores (moderate evidence). Conclusions: DHA is biologically essential during the first 1000 days, but its clinical impact depends on timing, dose, baseline status, and prematurity-related context. The balance between DHA and ARA, rather than DHA supplementation alone, emerges as a key determinant of clinical efficacy, supporting a shift toward precision-based nutritional strategies in early life. Full article

Insulin acts in the brain to promote satiety. Aging individuals may have brain insulin resistance and altered appetite perceptions. However, it is unclear if exercise impacts cerebral reward centers and appetite perception in middle-aged to older individuals. Purpose: To assess whether a single exercise bout alters cerebral blood flow (CBF) in reward centers in relation to appetite perceptions. Methods: Fifteen sedentary adults (12F; ~56 ± 2y; ~31 ± 1 kg/m²) completed a control and acute exercise condition (70% maximal oxygen consumption) in a randomized, counterbalanced order in the evening. Following an overnight fast, CBF in the accumbens, thalamus, and amygdala (pCASL MRI) was evaluated before and after intranasal insulin spray (INI, 40 IU) administration. Plasma glucose and insulin as well as an appetite visual analog scale (VAS) were assessed at fasting, 30, and 90 min post-INI, as well as at 30 min intervals of a 120 min 75 g oral glucose tolerance test (OGTT). Total area under the curve (tAUC) was calculated. Results: Exercise tended to lower blood glucose (p = 0.072) and plasma insulin (p = 0.007) tAUC, compared with rest. Exercise also raised right thalamus (p = 0.029) and left amygdala CBF (p = 0.023). The rise in fasting CBF in these regions, and the accumbens, correlated with reduced insulin tAUC (r = −0.55 to −0.73, p < 0.050). Although there was no difference in hunger, satisfaction, fullness, or prospective food consumption after exercise, changes in INI-stimulated thalamus CBF related to fullness tAUC after exercise (r = −0.57, p = 0.044). Conclusions: A single exercise bout might increase fasting CBF in some brain regions associated with appetite perception through a potential insulin-related mechanism. Full article

Quinoline-2,4-dione derivatives represent an essential class of heterocycle scaffolds that have demonstrated wide applications in modern drug discovery. However, the efficient construction of 3,3-difluoro-quinoline-2,4-diones with broad substrate generality remains a significant challenge and has not yet been reported. Herein, we developed the nickel-catalyzed intramolecular radical cyclization of 2-bromo-2,2-difluoro-N-(2-cyanoaryl)acetamides to achieve various 3,3-difluoro-quinoline-2,4-diones in good yields. The scalability and practical applicability of this method were demonstrated through large-scale reactions. Full article

A conceptually consistent understanding is sought for the interactions sampled by the imaginary cubic oscillator with potential $V^{\left(ICO\right)}\left(x\right)=\mathrm{i}{x}^3$, which is by itself not acceptable as a meaningful quantum model due to a combination of its non-Hermiticity, unboundedness, and most of all the Riesz-basis non-diagonalizability of the Hamiltonian, known as its intrinsic exceptional point (IEP) feature. For the purposes of a perturbation-theory-based simulation of the emergence of such a singular system, a simplified (though not too strictly related) toy-model Hamiltonian is proposed. It combines an $N-$point discretization of the real line of coordinates with an ad hoc interaction in a two-parametric N-by-N-matrix Hamiltonian $H=H^{\left(N\right)}(A,B)$. After such a simplification, one can still encounter a somewhat weaker form of non-diagonalizability at the conventional Kato’s exceptional-point (EP) limit of parameters $(A,B)\to (A^{\left(EP\right)},B^{\left(EP\right)})$. The IEP-non-diagonalizability phenomenon itself appears mimicked by the less enigmatic EP degeneracy of the discrete toy model, especially at large $N\gg 1$. What we gain is that, in contrast to the IEP case, the regularization of the simplified toy model in vicinity to the black conventional EP becomes feasible. Full article

In this paper, we consider a discrete equation in natural numbers of the form $x=\mathrm{count}(d,x)+n$, where n is a natural number, and $\mathrm{count}(d,x)$ is the number of occurrences of the digit $d\in \{0,1,\dots ,9\}$ in the decimal representation of the number x, and estimate the cardinality of the set of its solutions. As a result of the study, it is proved that for each natural number n and each digit $d\in \{2,3,\dots ,9\}$, the number of natural solutions of this discrete equation does not exceed two. It is established that in the case $d=1$, for each natural number n, the number of natural solutions of this discrete equation does not exceed three. It is constructively proved by developing an appropriate algorithm that in the case $d=0$, for each natural number k there exists a natural number $n_k$, such that the number of different natural solutions to the equation $x=\mathrm{count}(0,x)+n_k$, even written in decimal notation using no more than three digits such as 0, 8, 9, and having the same number of digits, is not less than k. We also demonstrate the application of the results and of the technique developed and presented in this paper to a system of equations describing the magic state of a special table of numbers, which strengthens and complements some recently obtained results. Full article

Intranasal drug delivery represents a transformative “backdoor” to the brain, bypassing the blood–brain barrier (BBB) that bars 98% of small molecules and nearly all large biopharmaceuticals. By harnessing the unique anatomy of the olfactory and trigeminal nerves, therapeutics can travel directly from the nasal cavity to the central nervous system, achieving therapeutic concentrations without the systemic toxicity of traditional routes. Clinical and preclinical evidence highlight the efficacy of intranasal insulin (INI) in treating Alzheimer’s disease (AD) and delirium, with studies showing significant improvements in cognitive scores and reduced hospital stays (7.9 vs. 12.9 days; p = 0.014). Additionally, other peptides can be administered intranasally like oxytocin, neuropeptide Y, and novel metabolic modulators for neuroprotection and affective disorders (AD, autism, Down syndrome). Despite these promises, critical translational gaps remain, including anatomical differences between macrosmatic rodents and microsmatic humans, and significant sex-based dosing dimorphism. The ease of intranasal administration introduces profound bioethical dilemmas regarding neuroenhancement, authenticity, and informed consent in vulnerable populations. The current literature concludes that realizing the full potential of nose-to-brain (N2B) therapy requires a commitment to precision medicine, utilizing specialized delivery devices and objective biomarkers to ensure safe and equitable clinical application. Full article

This paper is devoted to the introduction and systematic study of $(P,Q)$-normal operators in the context of semi-Hilbertian spaces, where P and Q are non-constant complex polynomials in one variable. This class generalizes the well-known notion of polynomially normal operators and offers a natural setting to study their structural properties in spaces endowed with a semi-inner product induced by a positive operator. We establish fundamental properties of $(P,Q)$-normal operators, including conditions for commutativity with respect to the $\mathbf{A}$-adjoint and relations to other classes of $\mathbf{A}$-operators. Several examples are provided to illustrate the theory and demonstrate how $(P,Q)$-normality extends classical concepts in operator theory. Full article

This article is a survey of the results published so far on Ulam stability of functional equations in n-normed spaces and (n, β)-normed spaces. We present and examine them, highlighting some traps they contain and outlining potential straightforward generalizations. We also draw attention to certain symmetries present in the results discussed. In this way, we complement two earlier surveys on Ulam stability in two-normed spaces. Full article

Introduction: Rapid and reliable neurovascular imaging is critical for time-sensitive diagnosis in acute cerebrovascular disorders, yet conventional magnetic resonance imaging (MRI) workflows remain constrained by acquisition speed, motion sensitivity, and limited integration of physiological context. We introduce the Intelligent Neurovascular Imaging Engine (INIE), a sensor-informed, topology-aware framework that jointly optimizes accelerated data acquisition, physics-grounded reconstruction, and cross-scale physiological consistency. Methods: INIE combines adaptive sampling, structured low-rank (Hankel) priors, and topology-preserving objectives with multimodal physiological sensors and scanner telemetry, enabling phase-consistent gating and confidence-weighted reconstruction under realistic operating conditions. The framework was evaluated using synthetic phantoms, a translational porcine stroke recanalization model with repeated measures, and retrospective human datasets. Across $N_{\mathrm{runs}}=120$ acquisition–reconstruction runs derived from $N_{\mathrm{animals}}=18$ pigs with animal-level train/validation/test separation, performance was assessed using image quality, topological fidelity, and cross-modal consistency metrics. Multiple-comparison control was performed using Bonferroni/Holm–Bonferroni procedures. Results: INIE achieved acquisition acceleration exceeding 70% while maintaining high reconstruction fidelity (PSNR $\approx 35$–36 dB, SSIM $\approx 0.90$–0.92). Topology-aware analysis showed an approximately twofold reduction in Betti number deviation relative to baseline accelerated methods. Cross-modal validation in a PET subset demonstrated strong agreement between MRI-derived perfusion parameters and metabolic markers (Pearson $r\approx 0.9$). INIE improved large-vessel occlusion detection accuracy to approximately 93% and reduced automated time-to-decision to under three minutes. Conclusions: These results indicate that sensor-informed, topology-aware, closed-loop imaging improves the reliability and physiological consistency of accelerated neurovascular MRI and supports faster, more robust decision-making in acute cerebrovascular imaging workflows. Full article

Background: n-3 PUFA derived from marine sources, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exhibit potential for breast cancer prevention. In contrast, higher dietary intakes of n-6 PUFA, such as linoleic acid (LA), have been implicated in promoting mammary tumourigenesis. However, there is a need for further exploration into how n-3 PUFA influence breast cancer development in comparison to different amounts and sources of LA. Objective: The purpose of this study was to compare the effects of n-3 PUFA-enriched diets versus n-6 PUFA diets differing in LA content, including corn oil (50% LA) and safflower oil (70% LA), on mammary tumour development in a HER2+ breast cancer model. Methods: Using the HER2+ breast cancer MMTV-neu(ndl)YD5 transgenic mouse model, this study determined the effects of: (1) 10% w/w corn oil (CO, n-6 PUFA, n = 14), (2) 10% w/w safflower oil (SO, n-6 PUFA, n = 14), (3) 3% w/w menhaden oil + 7% w/w CO (3% FO 7% CO, n-3 PUFA, n = 12), and (4) 3% w/w menhaden oil + 7% w/w SO (3% FO 7% SO, n-3 PUFA, n = 14) on puberty onset, tumour incidence, tumour volume, and tumour number in utero until 20 weeks of age. Results: Mice fed the n-3 PUFA-enriched diets showed a lower trajectory of tumour development compared to the n-6 PUFA diets, although the differences for palpated tumour volume and number over time reached significance only between the 10% CO and 3% FO 7% CO groups. This suggests that high LA content in CO may represent a threshold for promoting tumour growth whereby further LA content marginally influences additional tumour development. Exposure to the CO n-6 PUFA diet further resulted in earlier onset of puberty compared to the n-3 PUFA-enriched diet containing CO. To investigate the underlying mechanisms, a qPCR analysis of mammary glands and tumour tissue revealed that the n-3 PUFA diets downregulated the expression of pro-tumourigenic immune markers, including CD206 and F4/80 in the mammary glands and the cannabinoid receptor CB2 in tumours, compared to the n-6 PUFA diets. Conclusions: These findings indicate that the presence of dietary n-3 PUFA plays a key role in modulating mammary tumour development, which may be further influenced by the underlying n-6 PUFA background. The associated changes in immune markers suggest that n-3 PUFA exert anticancer effects in part by shifting the tumour immune microenvironment toward an anti-tumour phenotype and modulating cannabinoid receptor signalling. Collectively, this work informs future human studies investigating the role of dietary fat composition in breast cancer risk. Full article

Voltage stability assessment under transmission contingencies is traditionally performed using severity-based indices evaluated on isolated outage scenarios. While effective for identifying extreme events, such approaches provide limited insight into which transmission corridors structurally govern voltage-stress behavior across the full contingency space. This paper introduces a persistence-based diagnostic framework for voltage stability assessment under exhaustive $N-1$ line contingencies, using the Fast Voltage Stability Index (FVSI) as a base indicator. Rather than ranking lines by instantaneous severity, the proposed methodology identifies dominant transmission lines—defined as those attaining the maximum FVSI in each convergent contingency—and aggregates these outcomes statistically to quantify dominance persistence, conditional severity, and dispersion. A dominance concentration metric ($k_{90}$) is introduced to measure how many transmission corridors are sufficient to explain the majority of dominant voltage-stress events. The framework is applied to IEEE 14, 30, and 118-bus benchmark systems under exhaustive $N-1$ enumeration. Results reveal a clear phenomenon of dominance collapse: as system size increases, dominant voltage-stress outcomes concentrate onto an extremely small set of transmission corridors. While IEEE 14 exhibits partial dominance dispersion ($k_{90}=2$), both IEEE 30 and IEEE 118 demonstrate near-total dominance collapse ($k_{90}=1$), where a single corridor governs more than 90% of dominant FVSI events. The proposed approach is fully deterministic, scalable, and independent of control or optimization assumptions, making it well-suited for planning-stage screening, monitoring prioritization, and pre-filtering of large-scale contingency studies. By shifting voltage stability analysis from severity-only screening to persistence-based structural diagnosis, this work provides new insight into vulnerability concentration in modern transmission networks. Full article

Background: Structured lipids, composed of re-esterified triacylglycerols containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and medium-chain fatty acids, may influence metabolism and endurance performance. This trial aimed to evaluate the effects of eight weeks of structured lipid supplementation on substrate utilization, erythrocyte fatty acid content, and endurance performance in healthy untrained men. Methods: In a double-blind, placebo-controlled, randomized design, 36 participants (18 per group) received either structured lipids or placebo supplementation for eight weeks. Pre- and post-supplementation assessments included maximal oxygen uptake, time to exhaustion, substrate oxidation during exercise at 65% VO_2max, and erythrocyte membrane fatty acid content. Non-parametric statistical methods were used to analyze within- and between-group differences. Results: After supplementation, the structured lipids group showed statistically significant within-group changes in substrate utilization, including lower respiratory exchange ratio and higher percentage fat oxidation, total fat oxidation, and mean fat oxidation rate. Statistically significant increases were also observed in erythrocyte EPA + DHA content and time to exhaustion. Compared with the placebo group, the structured lipids group showed statistically significant post-intervention differences in substrate oxidation, erythrocyte EPA + DHA levels, and time to exhaustion. Conclusions: Eight weeks of structured lipid supplementation increased erythrocyte membrane EPA and DHA and enhanced fat oxidation during moderate-intensity exercise in untrained men. Although endurance performance improved, the change was within natural variability and showed substantial interindividual differences. Further rigorously controlled studies are needed to determine whether these metabolic adaptations yield meaningful functional benefits. Full article

Objectives: The objective of this study was to evaluate the effect of 21-day dietary omega-3 fatty acid supplementation on the levels of postexercise inflammation response, oxidative stress, and selected exerkine secretion among physically active young men. Methods: In a randomized double-blind study, 24 physically active men were assigned to two groups: a supplementation group (n = 12), receiving 3250 mg of n-3 polyunsaturated fatty acids (PUFAs) daily, and a placebo group (n = 12). Blood samples were collected before and after twenty-one days of dietary supplementation to measure total fatty acids and inflammatory markers, including IL-1β, IL-6, IL-10, BDNF, and FGF23. Results: After 21 days of n-3 fatty acid supplementation, there were no significant changes in anaerobic performance parameters. However, significant interactions were found in the systemic immune-inflammation index (SII), FGF-23, IL-1β, IL-1Ra, IL-6, and IL-10 in response to exercise and supplementation. Conclusions: 21 days of n-3 fatty acid supplementation modified PUFA content and influenced inflammation status, but did not affect maximal anaerobic performance. Full article

Let $\mathcal{Z}{\left(\mathcal{R}\right)}^{\prime }$ denote the set of all elements in the ring $\mathcal{R}$ that are neither zero nor units, where $\mathcal{R}$ is assumed to be a commutative ring with a multiplicative identity satisfying $1\ne 0.$ Two distinct vertices w and $\kappa$ are defined to be adjacent if and only if $\kappa$ does not lie in the ideal generated by w in $\mathcal{R},$ that is, $\kappa \notin w\mathcal{R},$ and simultaneously, w does not lie in the ideal generated by $\kappa$ in $\mathcal{R},$ that is, $w\notin \kappa \mathcal{R}.$ The cozero-divisor graph of $\mathcal{R},$ denoted by ${\Gamma }^{\prime }\left(\mathcal{R}\right),$ is an undirected graph in which the vertices are given by the set $\mathcal{Z}{\left(\mathcal{R}\right)}^{\prime }.$ This article presents a comprehensive evaluation of both the Euler Sombor index and the average Sombor index for the graphs ${\Gamma }^{\prime }\left({\mathbb{Z}}_n\right)$ corresponding to various values of $n.$ Full article

N-Alkyl deoxynojirimycin-derived drugs, belonging to the class of iminosugars, are well-known for their α-glucosidase inhibitory activity. N-Butyl-deoxynojirimycin (N-butyl-DNJ; NB-DNJ; also known as miglustat or UV-1) has been developed for the treatment of type 1 Gaucher disease and Niemann–Pick disease type C as Zavesca^®. Furthermore, it behaves as a host-targeted glucomimetic that inhibits endoplasmic reticulum α-glucosidase I and II (GluI and GluII, respectively) enzymes, resulting in improper glycosylation and misfolding of viral glycoproteins; thus, it is a potential antiviral agent. It is studied against a broad range of viruses in vitro and in vivo; however, its utility as antiviral has not been fully explored. Other N-alkylated congeners of DNJ are in preclinical and clinical studies for diverse viral infections. The iminosugar N-9′-methoxynonyl-1-deoxynojirimycin (MON-DNJ or UV-4) is probably the most studied and potent inhibitor of α-Glu I and α-Glu II in clinical trials. It is often studied in the form of its hydrochloride salt (UV-4B) and has broad-spectrum activity against diverse viruses, including dengue and influenza. In clinical trials, it was found to be safe at all doses tested up to 1000 mg. In this paper, an overview on N-alkyl derivatives of DNJ is reported, focusing on their antiviral activity. The literature search was carried out by means of three literature databases, i.e., PubMed/MEDLINE, Google Scholar, and Scopus, screened using different keywords. A brief history of the discovery of their usefulness as antivirals is given, as well as the most recent studies on new compounds belonging to this class. Since different names are often used for the same compound, we tried to dissipate confusion and bring some order to this jumble of names. Specifically, in the tables, all the diverse names used to identify each compound, were reported. Full article