Advancing Open Science

Arrhythmogenic cardiomyopathy (ACM) is a cardiac disorder manifesting through electrical and contractile dysfunction of the ventricles, characterized by fibro-fatty substitution of the myocardium. Cardiac mesenchymal stromal cells (CMSCs) are key contributors to this remodeling. In clinical management, several pharmacological approaches address ACM arrhythmias and heart failure, but, to date, none specifically target fibro-adipose replacement. Despite genetic origin, several studies have reported that non-genetic aspects influence ACM phenotype, including epigenetic factors. Little is known about their mechanisms in ACM and their potential therapeutic applications. In this work, we aimed to test whether, by perturbing the epigenetic landscape of ACM CMSCs, we could influence their propensity to fibro-fatty differentiation. We conducted a hypothesis-free screening of 157 epigenetic drugs on CMSCs, isolated from ACM patients. Through fluorescence assays, we evaluated lipid droplet accumulation, collagen deposition, and cell viability. Of the 157 drugs screened, five (splitomicin, suberohydroxamic acid, CPTH6, BVT-948, and PBIT) attenuated adipogenic differentiation of ACM CMSCs, with BVT-948 and CPTH6 also reducing collagen production. Overall, this study identified specific epigenetic drugs that were effective in reducing the fibro-fatty phenotype of ACM stromal cells, thus offering potential for adjunctive therapies in the clinical management of ACM patients.

Developing new materials for human cartilage replacement is a hot research topic. These materials have multiple properties of interest, so selecting a new material (hydrogel) is a multi-attribute decision-making problem. A case study illustrates the application of a structured approach and tools to solve this problem type. Ten hydrogels, most of which are new formulations, were evaluated based on three attributes. The weights assigned to the attributes were identified using three methods from the literature, in addition to those previously assigned by an expert. Since the hydrogel properties showed some variability, Monte Carlo simulations were carried out using triangular distribution. Ten thousand decision matrices were built and 10,000 rankings were generated by each of the ten multicriteria decision-making methods employed in this study. Ranking similarity was evaluated through the PS index, whose values ensure consistency and reliability of the results achieved. Rank acceptability and pairwise indexes were used to identify the most promising hydrogels. Two hydrogels were identified as the most promising for further study, for any of the four sets of weights used. Both are annealed nanocellulose-reinforced polyvinyl alcohol and pyrrolidone hydrogels. The robustness of this result is supported on the values of acceptability and pairwise indexes.

Bioactive peptides (BAPs) from dairy products have garnered increasing attention as natural agents with health-promoting properties, including antihypertensive, antioxidant, antimicrobial, immunomodulatory, opioid, and antidiabetic activities. This systematic review synthesizes research published between 2014 and 2024, retrieved from Scopus and PubMed, and selected according to PRISMA guidelines. A total of 192 studies met the inclusion criteria, collectively reporting over 3200 distinct peptides, with antihypertensive sequences, predominantly angiotensin-converting enzyme (ACE) inhibitors, constituting the largest category (n = 1237). β-casein was the principal precursor across bioactivities, followed by αs1-casein, β-lactoglobulin, and α-lactalbumin. Peptides were primarily produced via enzymatic hydrolysis, microbial fermentation, and gastrointestinal digestion, with peptide profiles influenced by the type of milk, microbial strains, and processing conditions. While cow’s milk remained the dominant source, investigations into goat, sheep, camel, buffalo, and donkey milk revealed species-specific biopeptides. Recent advances in proteomics have enhanced peptide identification and bioactivity prediction, enabling the discovery of novel sequences. These findings underscore the significant potential of dairy-derived BAPs as functional food components and nutraceutical ingredients, while highlighting the need for further in vivo validation, bioavailability studies, and broader exploration of underrepresented milk sources.

This study systematically investigates settlement sites that record living patterns of ancient humans, aiming to reveal the interactive mechanisms of human–environment relationships. The core issues of landscape archeology research are the surface spatial structure, human spatial cognition, and social practice activities. This article takes the Han Dynasty settlement site in Sanyangzhuang, Neihuang County, Anyang City, Henan Province, as a typical case. It comprehensively uses ArcGIS 10.8 spatial analysis and remote sensing image interpretation techniques to construct spatial distribution models of elevation, slope, and aspect in the study area, and analyzes the process of the Yellow River’s ancient course changes. A regional historical geographic information system was constructed by integrating multiple data sources, including archeological excavation reports, excavated artifacts, and historical documents. At the same time, the sequences of temperature and dry–wet index changes in the study area during the Qin and Han dynasties were quantitatively reconstructed, and a climate evolution map for this period was created based on ancient climate proxy indicators. Drawing on three dimensions of settlement morphology, architectural spatial organization, and agricultural technology systems, this paper provides a deep analysis of the site’s spatial cognitive logic and the ecological wisdom it embodies. The results show the following: (1) The Sanyangzhuang Han Dynasty settlement site reflects the efficient utilization strategy and environmental adaptation mechanism of ancient settlements for land resources, presenting typical scattered characteristics. Its formation mechanism is closely related to the evolution of social systems in the Western Han Dynasty. (2) In terms of site selection, settlements consider practicality and ceremony, which can not only meet basic living needs, but also divide internal functional zones based on the meaning implied by the orientation of the constellations. (3) The widespread use of iron farming tools has promoted the innovation of cultivation techniques, and the implementation of the substitution method has formed an ecological regulation system to cope with seasonal climate change while ensuring agricultural yield. The above results comprehensively reflect three types of ecological wisdom: “ecological adaptation wisdom of integrating homestead and farmland”, “spatial cognitive wisdom of analogy, heaven, law, and earth”, and “agricultural technology wisdom adapted to the times”. This study not only deepens our understanding of the cultural value of the Han Dynasty settlement site in Sanyangzhuang, but also provides a new theoretical perspective, an important paradigm reference, and a methodological reference for the study of ancient settlement ecological wisdom.

Since the early twentieth century, quantum mechanics has sought an interpretation that offers a consistent worldview. In the course of that, many proposals were advanced, but all of them introduce, at some point, interpretation elements (semantics) that find no correlate in the formalism (syntactics). This distance from semantics and syntactics is one of the major reasons for finding so abstruse and diverse interpretations of the formalism. To overcome this issue, we propose an alternative stochastic interpretation, based exclusively on the formal structure of the Schrödinger equation, without resorting to external assumptions such as the collapse of the wave function or the role of the observer. We present four (mathematically equivalent) mathematical derivations of the Schrödinger equation based on four constructs: characteristic function, Boltzmann entropy, Central Limit Theorem (CLT), and Langevin equation. All of them resort to axioms already interpreted and offer complementary perspectives to the quantum formalism. The results show the possibility of deriving the Schrödinger equation from well-defined probabilistic principles and that the wave function represents a probability amplitude in the configuration space, with dispersions linked to the CLT. It is concluded that quantum mechanics has a stochastic support, originating from the separation between particle and field subsystems, allowing an objective description of quantum behavior as a mean-field theory, analogous, but not equal, to Brownian motion, without the need for arbitrary ontological entities.

Performance of percutaneous coronary intervention (PCI) for bifurcation lesions involves complex decision-making informed by anatomic, hemodynamic, technical, and clinical factors. Building on the procedural foundations discussed in the companion paper in this two-part series, this second paper focuses on advanced considerations in bifurcation PCI. Factors associated with side branch (SB) compromise are discussed, including bifurcation angle and distribution of plaque location, along with strategies for SB protection and SB rewiring. Outcomes of landmark randomized controlled trials of provisional versus two-stent approaches, as well as specific two-stent techniques, are summarized. Based on these factors, an algorithmic approach for bifurcation PCI is outlined. Lastly, the use of drug-coated balloons, dedicated bifurcation stents, bioresorbable vascular scaffolds, bioadaptor stents, physiologic testing, intravascular imaging, and other emerging innovations are explored to provide a perspective on the future of bifurcation PCI.

This experiment investigated the mechanical performance and acid resistance (when subjected to 28 days of exposure to sulfuric and nitric acid of five percent) of ambient-cured geopolymer concrete. Geopolymer concrete (GPC)—which is produced by using industrial by-products, including fly ash and ground granulated blast furnace slag (GGBS)—is a low-carbon and strong substitute of Ordinary Portland Cement (OPC). This experiment examines the mechanical and acid-resisting properties of ambient GPC with different GGBS (10, 30, and 50 percent) contents. The compressive, tensile, and flexural strengths were measured at 7, 14, and 28 days, and durability was measured under an exposure of 5% sulfuric and nitric acids. X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed that gypsum and ettringite were formed by sulfuric acid that weakened the structure, whereas surface decalcification was mostly caused by nitric acid. Mixes with a high fly ash content had more amorphous structures and better acid resistance, whereas those having high GGBS contents had high early strength because of high densities of the C–A–S–H gel. The findings indicate a strength–durability trade-off, which can be used to control the optimized mix design to produce sustainable and long-term infrastructure.

This paper presents Multi_mil, a multilingual annotated corpus designed for the analysis of information operations in military discourse. The corpus consists of 1000 texts collected from social media and news platforms in Russian, Kazakh, and English, covering military and geopolitical narratives. A multi-level annotation scheme was developed, combining entity categories (e.g., military terms, geographical references, sources) with pragmatic features such as information operation type, emotional tone, author intent, and fake claim indicators. Annotation was performed manually in Label Studio with high inter-annotator agreement (κ = 0.82). To demonstrate practical applicability, baseline models and the proposed Onto-IO-BERT architecture were tested, achieving superior performance (macro-F1 = 0.81). The corpus enables the identification of manipulation strategies, rhetorical patterns, and cognitive influence in multilingual contexts. Multi_mil contributes to advancing NLP methods for detecting disinformation, propaganda, and psychological operations.