Search Results (152)

This study explores the identification, characterization, and biological evaluation of angiotensin I-converting enzyme (ACE)-inhibitory peptides derived from enzymatic hydrolysates of crucian carp swim bladders. Following sequential purification by size-exclusion and reversed-phase chromatography, two bioactive peptides—Hyp-Gly-Ala-Arg (Hyp-GAR) and Gly-Ala-Hyp-Gly-Ala-Arg (GA-Hyp-GAR)—were identified using ultra-high-performance liquid chromatography coupled with linear ion trap–Orbitrap tandem mass spectrometry. The synthetic peptides demonstrated potent ACE-inhibitory activity in vitro, with IC₅₀ values of 12.2 μM (Hyp-GAR) and 4.00 μM (GA-Hyp-GAR). Molecular docking and enzyme kinetics confirmed competitive inhibition through key interactions with ACE active site residues and zinc coordination. In vivo antihypertensive activity was evaluated in spontaneously hypertensive rats, revealing that GA-Hyp-GAR significantly reduced systolic blood pressure in a dose-dependent manner. At a dose of 36 mg/kg, GA-Hyp-GAR reduced systolic blood pressure by 60 mmHg—an effect comparable in magnitude and timing to that of captopril. Mechanistically, GA-Hyp-GAR modulated levels of angiotensin II, bradykinin, endothelial nitric oxide synthase, and nitric oxide. A 90-day subchronic oral toxicity study in mice indicated no significant hematological, biochemical, or histopathological alterations, supporting the peptide’s safety profile. These findings suggest that GA-Hyp-GAR is a promising natural ACE inhibitor with potential application in functional foods or as a nutraceutical for hypertension management. Full article

Computational models of peritoneal dialysis (PD) are increasingly useful for optimizing treatment in patients with kidney disease requiring dialysis (KDRD). However, although several mathematical models have been developed in the past few decades, a direct comparison of the models’ accuracy with respect to predicting in vivo data is needed to further create robust personalized models. Here, we used a dataset obtained in a previous in vivo experimental model of PD in pigs (23 sessions of 4 h 2 L dwells in four pigs) and humans (20 sessions in 20 patients) to compare six computational models of PD: the Graff model (UGM), the three-pore model (TPM), the Garred model (GM), and the Waniewski model (WM), as well as two variations of these (UGM-18, SWM). We conducted this comparison to predict the dialysate concentrations of key uremic toxins and electrolytes (four in humans) throughout a 4 h dwell. The model predictions can provide insight into inter-individual differences in ultrafiltration, which are critical for tailoring PD regimens in KDRD. While TPM offered improved physiological reality, its computational cost suggests a trade-off between model complexity and clinical applicability for real-time or portable kidney support systems. In future applications, such models could provide adaptive PD regimens for tailored care based on patient-specific toxin kinetics and fluid dynamics. Full article

Operating room (OR) scheduling problems are often addressed using deterministic models that assume surgery durations are known in advance. However, such assumptions fail to reflect the uncertainty that often occurs in real surgical environments, especially during the surgery and recovery stages. This study focuses on a robust scheduling problem involving a three-stage surgical process that includes pre-surgery, surgery, and post-surgery stages. The scheduling needs to coordinate multiple resources—pre-operative holding unit (PHU) beds, ORs, and post-anesthesia care unit (PACU) beds—while following a strict no-wait rule to keep patient flow continuous without delays between stages. The main goal is to minimize the makespan and improve schedule robustness when surgery and post-surgery durations are uncertain. To solve this problem, we propose a Genetic Algorithm for Robust Scheduling (GARS), which evaluates solutions using a scenario-based robustness criterion derived from multiple sampled instances. GARS is compared with four other algorithms: a deterministic GA (GAD), a random search (BRS), a greedy randomized insertion and swap heuristic (GRIS), and an improved version of GARS with simulated annealing (GARS_SA). The results from different problem sizes and uncertainty levels show that GARS and GARS_SA consistently perform better than the other algorithms. In large-scale tests with moderate uncertainty (30 surgeries, α = 0.5), GARS achieves an average makespan of 633.85, a standard deviation of 40.81, and a worst-case performance ratio (WPR) of 1.00, while GAD reaches 673.75, 54.21, and 1.11, respectively. GARS can achieve robust performance without using any extra techniques to strengthen the search process. Its structure remains simple and easy to use, making it a practical and effective approach for creating reliable and efficient surgical schedules under uncertainty. Full article

Background: In the United States, approximately 1 in 5 children experience comorbidities with mental illness, including depression and anxiety, which lead to poor general health outcomes. Adolescents with substance use disorders exhibit high rates of co-occurring mental illness, with over 60% meeting diagnostic criteria for another psychiatric condition in community-based treatment programs. Comorbidities are influenced by both genetic (DNA antecedents) and environmental (epigenetic) factors. Given the significant impact of psychiatric comorbidities on individuals’ lives, this study aims to uncover common mechanisms through a Genome-Wide Association Study (GWAS) meta-meta-analysis. Methods: GWAS datasets were obtained for each comorbid phenotype, followed by a GWAS meta-meta-analysis using a significance threshold of p < 5E−8 to validate the rationale behind combining all GWAS phenotypes. The combined and refined dataset was subjected to bioinformatic analyses, including Protein–Protein Interactions and Systems Biology. Pharmacogenomics (PGx) annotations for all potential genes with at least one PGx were tested, and the genes identified were combined with the Genetic Addiction Risk Severity (GARS) test, which included 10 genes and eleven Single Nucleotide Polymorphisms (SNPs). The STRING-MODEL was employed to discover novel networks and Protein–Drug interactions. Results: Autism Spectrum Disorder (ASD) was identified as the top manifestation derived from the known comorbid interaction of anxiety, depression, and attention deficit hyperactivity disorder (ADHD). The STRING-MODEL and Protein–Drug interaction analysis revealed a novel network associated with these psychiatric comorbidities. The findings suggest that these interactions are linked to the need to induce “dopamine homeostasis” as a therapeutic outcome. Conclusions: This study provides a reliable genetic and epigenetic map that could assist healthcare professionals in the therapeutic care of patients presenting with multiple psychiatric manifestations, including anxiety, depression, and ADHD. The results highlight the importance of targeting dopamine homeostasis in managing ASD linked to these comorbidities. These insights may guide future pharmacogenomic interventions to improve clinical outcomes in affected individuals. Full article

In the current era of heightened awareness regarding the impact of food choices, there has been a noticeable shift towards revisiting traditional ingredients. Following the growing interest in ancient grains, this study evaluated their potential use for enriching modern wheat dough and bread. The effects of substituting 20% of wheat flour with the bran of seven ancient grains on dough’s rheological properties and bread quality were assessed. The bran-enriched doughs maintained high stability (ST) values and showed an enhanced elastic behavior compared to the control. Nonetheless, a reduction in dough extensibility (E) was also noted. In terms of bread measurements, all bran-enriched breads exhibited a lower specific volume and a darker crust and crumb compared to the control bread. However, not all of the bran breads showed a harder and chewier loaf texture. The composite breads also exhibited enhanced total dietary fiber (TDF) and polyphenol content. A sensory evaluation revealed that Garfagnana (GAR) and Norberto (NOR) bran-breads received the highest overall liking scores. In conclusion, the incorporation of ancient grain brans presents a promising approach to enhancing modern wheat doughs and breads, offering nutritional benefits without significantly compromising their sensory and textural properties. Full article

The tropical gar (Atractosteus tropicus) is a primitive freshwater fish of significant commercial importance in southeastern Mexico. However, its population is in danger due to habitat loss and overexploitation. Cultivation emerges as a viable reproductive management strategy; yet further studies are crucial to understanding molecular markers guiding reproductive management, differentiation, and sexual maturation in this species. We analyzed the expression of five sex-related genes (foxl2, sox9, cyp17a1, dmrt1, and cyp19a1) in the brain, liver, and gonads of adult A. tropicus (four females and five males). Methodologically, we collected samples and conducted RNA extraction, cDNA synthesis, and gene expression analysis using qPCR. The gonadal histology provided morphological context that reveals that the differential expression of genes establishes differences between sexes. The sexual phenotype of females is observed with the high expression of dmrt1, while in males, there is a reduction in the expression of dmrt1 and high levels of sox9, foxl2, and cyp17a1. Our findings establish dmrt1 and cyp19a1 as potential sex biomarkers and provide a molecular basis for developing sexing protocols in A. tropicus. Full article

Exposure to air pollution, especially fine particulate matter (PM2.5), is closely linked to various adverse health effects, particularly in the respiratory system. The present study was designed to investigate the lncRNA–mRNA interactions in PM2.5-induced lung cell injury using weighted gene co-expression network analysis (WGCNA). We downloaded the gene expression data of GSE138870 from the Gene Expression Omnibus (GEO) database and screened for differentially expressed lncRNAs and mRNAs. We constructed co-expression modules with WGCNA. Furthermore, functional enrichment analysis was also performed. We also constructed lncRNA–mRNA co-expression networks and lncRNA–mRNA-pathway networks to identify key regulatory relationships. The results revealed several modules significantly correlated with PM2.5-induced lung injury, such as the turquoise and blue modules. Genes within these modules were enriched in pathways related to signal transduction, metabolism, and cancer. Hub lncRNAs in the turquoise module, including LOC100129034 and CROCCP2, were found to be co-expressed with mRNAs involved in apoptosis and proliferation regulation. In the blue module, lnc-CLVS2-2 and GARS1-DT were connected to genes related to cell migration, invasion, and lung injury. These findings contribute novel perspectives to the molecular mechanisms involved in PM2.5-induced lung injury and suggest that WGCNA could be a valuable tool for predicting and understanding this disease process. Full article

This article delves into the perception of monastics from Larung Gar Buddhist Academy of Western China concerning the intertwining relationship between Buddhism and science, along with the impact of this perception on their worldview and life trajectory. Many monastics at Larung Gar Buddhist Academy initially held a high regard for science, dismissing Buddhism as superstition. However, upon gaining a comprehensive understanding of Buddhism through various opportunities, they came to believe that certain tenets of Buddhism are compatible with science, even suggesting that Buddhism could address some of the methodological and epistemological limitations of science and offer solutions to some issues that science is unable to resolve. This ultimately led them to embrace Buddhism and renounce worldly life. This study employs a case study to investigate the understanding of the relationship between Buddhism and science amongst the general public in contemporary China, an area underexplored by previous scholarship that predominantly concentrated on the philosophical scrutiny of the apologetic discourses towards the reconciliation between Buddhism and science of influential Buddhist ascetics and lay practitioners. Also, this study endeavors to demonstrate that despite the ongoing secularization of contemporary Chinese Buddhism in the “public sphere”, within the “private sphere” of Chinese Buddhism, there remain individuals who are pursuing the religious, sacred, and transcendental dimensions of Buddhism. Full article

At the beginning of the 21st century, there were sensational discoveries in two palaces located in Ciechanowice and Struga in Silesia (Poland). During their renovations, Renaissance fresco cycles of portraits of emperors from the Roman, medieval, and early modern times appeared under the layer of plaster in the representative dining rooms (27 in the palace in Struga and about 50 in the palace in Ciechanowice). They were painted in the 1580s (in Ciechanowice, the date is 1588) by the same unknown artist. This article is the first to attempt to establish the most important facts related to the creation of both fresco cycles. The frescoes were founded by representatives of influential Silesian Protestant nobility: Heinrich von Reichenbach (Ciechanowice) and Abraham von Czettritz und Neuhaus (Struga). Both nobles attended the funeral of Emperor Maximilian II, which took place in Prague in 1577. This is where they purchased a work by the Dutch printmaker, painter, and numismatist, Hubert Goltzius, Lebendige Bilder Gar Nach Aller Keysern […] (published in Antwerp in 1557), whose specially prepared copy had been solemnly presented to Emperor Maximilian II in 1562. The book contains 133 monochrome woodcut illustrations with portraits of emperors in circular frames by the Dutch artist Joss van Gietleughen, which—together with accompanying inscriptions—were used as models for fresco paintings in both Silesian palaces. The foundation of the cycles of portraits of the emperors of the Roman Empire and the Holy Roman Empire of the German Nation in the representative halls of the palaces in Ciechanowice and Struda, which ended with a joint representation of Emperor Maximilian II and the King of Spain, Philip II Habsburg, was a way to show the gratitude of both prominent and wealthy Protestant nobles towards Emperor Maximilian II. During his reign, imperial power was the source and guarantee of religious freedoms for Protestants in Silesia. It is significant that both cycles left out the person of emperor regnant, Rudolf II, who soon after assuming the imperial throne abandoned his father’s tolerant policy towards Protestants. Although the author of both series of frescoes was probably a local painter, they are a unique artistic realization not only in Silesia but also in the whole of Central Europe, and they can only be compared to the popular Renaissance portrait galleries of “famous men” (uomini famosi). Full article

Water release is a crucial aspect when considering cleaning effects on water-sensitive materials. In conservation practice, a water-based cleaning method which limits water release is very often needed. Unfortunately, this is not accompanied by an appropriate measure of the effectively released water. In this paper, water release has been measured by comparing traditional cleaning formulations, such as paper pulp and sepiolite, with several gar gel formulations, used by both Italian and European conservators. The assessment has been carried out by the gravimetric method, using three different stone material specimens as reference: Noto calcarenite, Manciano sandstone and Black Bergamo limestone, whose porosity values and distributions are known. Moreover, water distribution has been evaluated by portable NMR tests. Different commercial agar gel products (Bresciani, CTS, Sigma), having different concentrations (3, 4, and 5%), application modes (rigid at room T or fluid warm gels, with and without inserting Japanese tissue paper), and geometry (horizontal in gravity force direction or vertical), have been compared to obtain a full scenario among different water release mechanisms present in real conservation works. The paper faces the important issue of preparing reproducible chemical or water pads as well, useful for further research aimed at comparing cleaning effects in heritage conservation. The most interesting quantitative results can be summarized as follows. The water release measured from paper pulp and sepiolite was found to be 2 to 4 times higher than from any tested agar gel. Water release decreases by increasing agar concentration; an increase in the agar concentration by 1% induces a decrease in water release in the range 16.98–66.88 g depending on the stone; the increase from 4% to 5% is more obvious with respect to that from 3% to 4%. It is possible to assess the effect of the presence of Japanese paper, which is able to reduce the water release from 18 to 76%, depending on the stone and on the agar used. The gravimetric results were also used in the preliminary calibration tests of a contact probe named System Unit Salinity Index (SUSI), recently patented and useful in providing humidity and salinity indexes in a given porous material. Full article

Background: This study aimed to support the end-of-shelf life specification (2.5 × 10¹⁰ virus particles [vp]) for the standard Ad26.COV2.S dose (5 × 10¹⁰ vp). Methods: This randomized, double-blind Phase 3 study evaluated immunogenicity, reactogenicity, and safety of several Ad26.COV2.S dose levels (range 1.25 to 9 × 10¹⁰ vp) in 1593 adults between June 2021 and July 2023. Results: Spike-binding antibody responses 28 days post-dose 1 were non-inferior for the 9 × 10¹⁰ vp, but not the 2.5 × 10¹⁰ vp group when compared with the standard dose. Non-inferiority was demonstrated in terms of spike-binding antibody responses 14 days post-dose 2 for each dose level, including the lowest dose level of 1.25 × 10¹⁰ vp, compared to 28 days after one dose and 14 days after two doses of the standard dose. Spike-binding antibody levels correlated well with virus neutralizing titers. There was no impact of pre-existing Ad26.COV2.S neutralizing titers on immunogenicity at any dose level. All dose levels were well tolerated. Conclusions: This study highlights the challenges associated with conducting clinical studies in a rapidly evolving environment and underscores the importance of platform data that can guide initial vaccine specifications such as shelf life during accelerated vaccine development. The present study supports the end-of-shelf life specifications for the approved Ad26.COV2.S dose, and could provide useful information in future vaccine developments using adenovirus vector vaccines. Full article

Throughout recent years, the implementation of nanoparticles into the microstructure of additively manufactured (AM) parts has gained great attention in the material science community. The dispersion strengthening (DS) effect achieved leads to a substantial improvement in the mechanical properties of the alloy used. In this work, an ex situ approach of powder conditioning prior to the AM process as per a newly developed fluidized bed reactor (FBR) was applied to a titanium-enriched variant of the NiCu-based Alloy 400. Powders were investigated before and after FBR exposure, and it was found that the conditioning led to a significant increase in the TiN formation along grain boundaries. Manufactured to parts via laser-based powder bed fusion of metals (PBF-LB/M), the ex situ FBR approach not only revealed a superior microstructure compared to unconditioned parts but also with respect to a recently introduced in situ approach based on a gas atomization reaction synthesis (GARS). A substantially higher number of nanoparticles formed along cell walls and enabled an effective suppression of dislocation movement, resulting in excellent tensile, creep, and fatigue properties, even at elevated temperatures up to 750 °C. Such outstanding properties have never been documented for AM-processed Alloy 400, which is why the demonstrated FBR ex situ conditioning marks a promising modification route for future alloy systems. Full article

Antioxidants derived from food by-products are known for their bioactive properties and impact on human health. However, the gastrointestinal behavior is often poor due to their degradation during digestion. The development of Ca(II)–alginate beads supplemented with biopolymers and enriched with cowpea (Vigna unguiculata) extract could represent a novel environmentally friendly technological solution to produce functional ingredients in the food industry. The present study evaluates the impact of in vitro digestion/fermentation by analyzing global antioxidant response (GAR), production of short-chain fatty acids (SCFAs) as a modulation of gut microbiota, and behavior of proton transverse relaxation times by low-field nuclear magnetic resonance (as an indicator of gelation state and characterization of microstructure). Results revealed that guar gum and cowpea protein preserved a high GAR of total phenolic compounds and antioxidant capacity by ABTS and FRAP methods after digestion/fermentation, promoting an adequate protection of the bioactives for their absorption. Alginate-based beads have great potential as prebiotics, with the guar gum-containing system contributing the most to SCFAs production. Finally, the overall higher mobility of protons observed in the intestinal phase agrees with structural changes that promote the release of phenolic compounds during this stage. Beads are excellent carriers of bioactive compounds (cowpea phenolic compounds and peptides) with potential capacities. Full article

Probiotics in aquaculture hold promise for enhancing fish health and growth. Due to their increased specificity and affinity for their host, indigenous probiotics may offer isolated and potentially amplified benefits. This study investigated the effects of Lactococcus lactis PH3-05, previously isolated from adults of tropical gar (Atractosteus tropicus), on the growth, survival, digestive enzyme activity, intestinal morphology, expression of barrier and immune genes, and intestinal microbiota composition in the larvae of tropical gar. Larvae were fed with live L. lactis PH3-05 concentrations of 10⁴, 10⁶, and 10⁸ CFU/g for 15 days alongside a control diet without probiotics. Higher concentrations of L. lactis PH3-05 (10⁶ and 10⁸ CFU/g) positively influenced larval growth, increasing hepatocyte area and enterocyte height. The 10⁶ CFU/g dose significantly enhanced survival (46%) and digestive enzyme activity. Notably, the 10⁸ CFU/g dose stimulated increased expression of muc-2 and il-10 genes, suggesting enhanced mucosal barrier function and anti-inflammatory response. Although L. lactis PH3-05 did not significantly change the diversity, structure, or Phylum level composition of intestinal microbiota, which was constituted by Proteobacteria, Bacteroidota, Chloroflexi, and Firmicutes, an increase in Lactobacillus abundance was observed in fish fed with 10⁶ CFU/g, suggesting enhanced probiotic colonization. These results demonstrate that administering L. lactis PH3-05 at 10⁶ CFU/g promotes growth, survival, and digestive health in A. tropicus larvae, establishing it as a promising indigenous probiotic candidate for aquaculture applications. Full article

This study was carried out to characterize the dynamics of forage accumulation during the regrowth of Mulatto grass submitted to rotational grazing strategies. The treatments corresponded to combinations between two pre-grazing conditions (95% and a maximum light interception during regrowth—LI_95% and LI_Max) and two post-grazing conditions (post-grazing heights of 15 and 20 cm), according to a 2 × 2 factorial arrangement and randomized complete block design, with four replications. Rates of leaf growth (LGR), stems growth (SGR), total growth (TGR), leaf senescence (LSR), grass accumulation (GAR) (kg·ha⁻¹·day⁻¹), and the senescence/canopy growth ratio during different stages of regrowth. There was no difference between the management strategies for TGR. However, a higher GAR was reported for pastures managed with LI_95% relative to LI_Max, of 161.7 and 120.2 kg DM ha⁻¹·day⁻¹, respectively. Pastures managed with LI_95% have a lower SGR in the intermediate and final regrowth period, reflecting the efficient control in the stalks production. On the other hand, in pastures managed, the LI_Max showed higher SGR and LSR in the final regrowth phase. Thus, the LAI was higher in pastures managed at LI_95% compared to those managed at LI_Max, of 163.9 and 112.7 kg DM ha⁻¹·day⁻¹, respectively. Mulatto grass pastures, which were managed at LI_95% pre-grazing, corresponded to approximately 30 cm in height, showed higher LAI, and ensured a low SGR throughout the regrowth period, constituting a more efficient management strategy. Full article