Search Results (1,918)

The limited capacity for cardiomyocyte proliferation in the adult human heart restricts its ability to recover from injury. Building on discoveries in regenerative model systems, such as zebrafish and neonatal mice, reactivation of a latent potential for cardiomyocyte proliferation is a strategy to promote therapeutic heart regeneration. Although cardiomyocyte proliferation remains modest even with the most effective mitogenic stimuli identified to date, evidence for a potential functional benefit in pre-clinical model systems has led to the initiation of several early-phase clinical programs. Here, we review insights from model organisms that inform the potential efficacy and limitations of therapeutic cardiomyocyte proliferation, systems to study human cardiomyocyte proliferation, and the natural history of cardiomyocyte proliferation in the human heart. We also examine the translational trajectory of selected discoveries, including therapeutic delivery modalities, and attendant safety concerns. Finally, we discuss critical challenges that will need to be addressed to enable successful clinical translation. Full article

This study explores a circular economy strategy for vineyard residue management through the conversion of pruning biomass into carbonaceous materials by hydrothermal carbonization (HTC) and pyrolysis (PYR), with and without iron (Fe) addition. A preliminary pot-based vegetation experiment was conducted as a screening assay to assess initial plant tolerance and exclude evident phytotoxic effects. Chlorophyll index values in grapevine leaves remained within physiological ranges across treatments and sampling dates, although no consistent treatment-related trends could be established. Overall, the results provide a physicochemical characterization of the carbonaceous materials derived from vineyard residues and demonstrate their initial compatibility with grapevine cultivation under controlled conditions. This work lays the groundwork at the material level for future, more comprehensive studies that integrate long-term soil, plant, and field assessments. Full article

Vinegar is a traditional fermented food of increasing industrial interest due to its nutritional, sensory, and bioactive properties. This study aimed to develop and optimize a controlled biotechnological process for vinegar production from the Algerian date cultivar Degla Beida, an abundant yet underexploited local resource. Indigenous Saccharomyces cerevisiae strains isolated from date fruits and Acetobacter sp. strains isolated from traditional date vinegar were employed as starter cultures in a two-stage submerged fermentation process, comprising alcoholic fermentation followed by acetic fermentation. Process optimization was carried out using Response Surface Methodology (RSM) based on a Central Composite Design (CCD), evaluating the effects of initial alcoholic degree (4–10% v/v) and yeast extract supplementation (0.2–0.5 g/L). The statistical models showed excellent fitting and predictive reliability (p < 0.0001; R² = 94.1–99.1%). Under optimal conditions (7% v/v initial alcohol, 0.2 g/L yeast extract, 30 °C, pH 5), the process yielded a maximum acetic acid concentration of 72 g/L after 11 days, with 80% fermentation efficiency and complete ethanol depletion. The optimized vinegar exhibited enhanced bioactive properties, with a total phenolic content of 620 mg GAE/100 mL and a DPPH radical scavenging activity of 78%, significantly higher than those of the unfermented juice. These results demonstrate the suitability of Degla Beida dates for vinegar production and highlight the potential of indigenous microbial resources for the sustainable valorization of local raw materials through controlled fermentation processes. Full article

To this date, the Fifth Generation (5G) of mobile communications has been deployed and has opened a great number of opportunities by increasing transmission rates (partialy through the use of MIMO systems), decreasing latency, providing the amount of bandwidth required for video services, Virual and Augmented Reality applications, and social media and providing a solid ground for the massive implementation of the Internet of Things (IoT), which we believe is still in its initial phases of development [...] Full article

The shift toward a circular economy (CE) holds a central position in solving, globally, the long-standing environmental degradation and resource scarcity. Innovative sustainable processes and products lie at the core of such a shift, but they often face challenges associated with technological, organizational, financial, and regulatory paradigms. To date, two leading facilitators have been identified: sophisticated digital technologies, such as Artificial Intelligence, the Internet of Things, and Big Data, together with the collaborative creation of value among diverse stakeholders. Although the implications of each of these enablers on sustainability are known to some extent, little is understood about how their interrelatedness can counteract implementation barriers and drive innovation. The systematic thematic literature review examines how organizations utilize digital technologies and stakeholder engagement to facilitate green innovation in Circular Economy (CE) systems. Based on Stakeholder Theory, the Technology-Organization-Environment (TOE) framework, and the Resource-Based View (RBV), this review examines how organizations leverage digital technologies and stakeholder engagement to foster green innovation within circular economy systems. Following the PRISMA 2020 guidelines, a structured search was conducted in Scopus and Web of Science, covering peer-reviewed journal articles published in English between 2013 and 2024. Using predefined inclusion and exclusion criteria, 84 studies were retained for analysis from an initial pool of 850 records. The review integrates findings from five thematic areas: collaborative innovation among stakeholders, the use of digital technology to advance sustainability, challenges associated with adopting circular-economy values, linkages between technology and stakeholders, and the consequences of innovation. The findings suggest that collaboration between diverse stakeholders, combined with integration with digital technologies, provides a synergistic approach to maximizing innovation outcomes, overcoming implementation challenges, and diffusing circular practice. Skillfully crafted initiatives augment organizational capacities, foster collaborative actions, and advance sustainability initiatives. Despite providing a comprehensive synthesis of existing research, this review is limited by its reliance on secondary data. A qualitative quality appraisal was conducted to support the interpretation of findings. This review was not registered and received no external funding. Future research should conduct empirical analyses of these relationships and develop inclusive frameworks to guide initiatives emerging from collaborative and digital platforms across a wide range of sectors within the circular economy. Full article

Global extreme poverty has fallen dramatically over the past two centuries, yet hundreds of millions remain impoverished, underscoring the need for scalable monitoring tools. In Mexico, poverty metrics are available only sporadically in terms of time and space (e.g., every 5 years at the municipal level), making it difficult for decision-makers to access reliable, up-to-date, and sufficiently detailed information, highlighting the need for higher-resolution, timely methods. To address this problem, we propose a two-stage approach that combines socioeconomic and Earth Observations-based data. Initially, a machine learning model maps census variables to official poverty indicators belonging to a multidimensional model, yielding fine-scale poverty estimates. A census-based model trained with eXtreme Gradient Boosting (XGBoost) achieved a determination coefficient ($R^2$) of approximately $0.842$, indicating strong agreement with official poverty figures and providing high-resolution proxies. Afterward, we use features based on remote observations to predict these poverty estimates at a 469 m grid scale. In this case, advanced foundation models outperformed other machine learning (ML) approaches, achieving an $R^2$ of $0.683$. While foundation models enable more accurate, fine-scale poverty mapping and could accelerate poverty assessments, their use comes at a heavy price in terms of carbon emissions. Full article

This research investigates ten sediment cores extracted from Holocene deposits in Labu, northern Temburong District, Brunei Darussalam, to provide an initial inventory of the encountered peat-forming environments. Proximate, ultimate, and geochemical analyses were performed, along with mineralogical characterisations and ¹⁴C radiocarbon dating, as well as preliminary palaeontological and palynological examinations of the peat and underlying substrate layers. Localised organic deposits, termed “peat pockets”, were identified, with the oldest found to have begun accumulating under topogenous-mire conditions during the Middle Holocene. This coincides with the Mid-Holocene sea-level rise, which is thought to have peaked at 6000–4500 years BP. However, our data suggest that sea level may have continued rising until approximately 2500 years BP, peaking between 2500 and 1700 years BP, followed by delta progradation in Temburong. These “peat pockets” gradually coalesced into larger topogenous mires associated with estuarine environments. Over time, they became less influenced by marine conditions and increasingly shaped by a freshwater regime, resembling an upper delta system, similar to the present-day landscape observed in Temburong. It is proposed that these mires transitioned from a topogenous to an ombrogenous phase approximately 250 to 320 years BP, as inferred through forward age extrapolation based on a constant accumulation rate. The findings support the hypothesis of inland coastline migration during the Middle Holocene, followed by retraction due to deltaic progradation in the Late Holocene. These fluctuations align with well-established sea-level changes driven by climatic variability. Full article

Trichorhinophalangeal syndrome type II (TRPS II) is a rare disease caused by a contiguous gene deletion in the 8q23.3–q24.11 region. Three genes (TRPS1, RAD21, and EXT1) are considered responsible for the most common clinical features, which include facial dysmorphism, ectodermal and skeletal anomalies, osteochondromas, and cognitive impairment. To date, seven patients with 8q23–q24 deletions not involving TRPS1 have been reported, with phenotypes overlapping TRPS II. In this paper, we present clinical and genetic aspects from three non-related patients with 8q23–q24 deletions, and we review the available testing strategies for such patients and their families. The deletions harbored by these patients have been identified through microarray, with two of them also undergoing initial MLPA evaluation. The observed clinical and genetic features are heterogeneous, and generally in keeping with known associations between the three main genes from the deleted region and the clinical manifestations of TRPS II. Particularly, the deleted regions vary substantially in size, genomic coordinates, and gene content, with one not including TRPS1, and another, with a more distal loss, not including either TRPS1 nor RAD21. By describing three new patients, we hope to enlarge the genetic and clinical landscape of TRPS II and 8q23–q24 deletions, and help identify further genotype–phenotype correlations. Full article

Background: Protein–energy wasting (PEW) is a major predictor of morbidity and mortality in patients with chronic kidney disease (CKD), even before the initiation of dialysis. Its multifactorial pathogenesis includes reduced dietary intake, chronic inflammation, metabolic acidosis, hormonal disturbances, and dysbiosis of the gut microbiota. Early recognition and targeted management are crucial for preventing muscle loss, functional decline, and adverse outcomes. Methods: This narrative review summarises and integrates current evidence from the literature on nutritional and metabolic interventions to prevent and treat protein–energy wasting in patients with nondialysis chronic kidney disease. Relevant clinical trials, meta-analyses, and experimental studies published up to date were evaluated, focusing on dietary strategies, metabolic modulation, physical exercise, and gut microbiome-targeted therapies. Results: Adequate energy and protein intake remain the cornerstone of PEW management, based on available clinical and observational evidence. Individualised diets emphasising high-quality and plant-based proteins, oral nutritional supplements, and ketoanalogues can attenuate muscle wasting. Correction of metabolic acidosis and inflammation enhances protein anabolism and nitrogen balance. Physical exercise acts synergistically with dietary interventions to preserve muscle mass and function. Novel approaches—such as modulating the gut–kidney axis with pre-, pro-, and postbiotics or supplementing with short-chain fatty acids—show promise in improving metabolic and inflammatory profiles. Conclusions: The management of PEW in nondialysis CKD requires a personalised approach that integrates nutrition, physical activity, metabolic correction and microbiome modulation. Early, coordinated intervention may help to slow the progression of CKD and improve patient survival and quality of life. Full article

Arbuscular mycorrhizal fungi (AMF) play a pivotal role in plant adaptation to arid ecosystems, yet their widespread agricultural use is constrained by the scarcity of high-quality, locally adapted inoculum. This study established a reliable monoxenic culture system for mass-producing an indigenous AMF isolate from the date palm (Phoenix dactylifera L.) rhizosphere in the Figuig oasis, southeastern Morocco. The isolate was identified as Rhizophagus irregularis based on spore morphology and Large Subunit ribosomal DNA (LSU rDNA) phylogeny. Two propagule types, surface-sterilized spores and mycorrhizal root fragments of Plantago lanceolata L., were compared for initiation of in vitro cultures on Ri T-DNA-transformed carrot (Daucus carota L.) hairy roots. By week 16, cultures initiated from mycorrhizal root fragments produced 1414 ± 65 spores per plate and showed significantly higher performance than spore-derived cultures in terms of propagule viability, root colonization, and hairy root growth. Propagule viability reached 84% and 68%, root colonization frequencies were 95% and 72%, and hairy root lengths averaged 81 and 63 cm in root fragment- and spore-derived cultures, respectively (p < 0.01). In a subsequent whole-plant assay using P. lanceolata, in vitro-produced spores induced markedly higher mycorrhizal colonization frequency (91.0 ± 1.6% compared with 74.8 ± 1.9%) and intensity (70.0 ± 1.6% compared with 55.0 ± 1.6%) than spores obtained from conventional trap cultures (p < 0.001). These results demonstrate that monoxenic root-organ culture using root fragments is a robust, reproducible method for generating abundant, contaminant-free, and functionally superior inoculum of native R. irregularis. This advance provides a solid platform for developing tailored bio-inoculants to enhance crop resilience and sustainability in arid and semi-arid agroecosystems. Full article

Growing evidence suggests that persistent oral infectious diseases (OIDs) contribute to systemic disease, highlighting the importance of understanding their pathogenic mechanisms. Conventional dental treatments, primarily mechanical debridement, surgical intervention, or antimicrobial therapy, often struggle to fully control inflammation or prevent progressive tissue destruction. The nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immunity, mediating the maturation of proinflammatory cytokines (IL-1β and IL-18) and the pyroptosis-inducing protein gasdermin D. Dysregulated or excessive activation of NLRP3 contributes to the initiation and progression of major oral diseases, including periodontitis, peri-implantitis, pulpitis, and oral mucosal inflammation. Despite growing interest in NLRP3, comprehensive and up-to-date reviews integrating its pathogenic mechanisms and therapeutic potential remain limited. This review summarizes current and past evidence on the role of the NLRP3 inflammasome in oral disease development, highlights emerging pharmacological strategies, and outlines future research directions. Existing studies demonstrate that microbial components and danger signals from injured tissues activate NLRP3, thereby amplifying inflammation, tissue degradation, and bone resorption. Preclinical studies indicate that inflammasome inhibitors and several natural compounds reduce tissue damage; however, their clinical translation remains limited. These findings emphasize the need for deeper understanding of NLRP3-mediated pathways, with translational and clinical research offering promising therapeutic opportunities for oral diseases. Full article

In recent years, the development of new diagnostic technologies, such as tandem mass spectrometry (MS/MS) and next-generation sequencing (NGS), has caused a veritable revolution in the diagnosis of genetic diseases, reducing time, cost, and invasiveness associated with prior diagnostic techniques. While MS/MS laid the foundation for the development of numerous, usually institutionally based, neonatal screening programs, NGS has gained traction in newborn screening (NBS), primarily through pilot projects and private funding across different countries. As a result, the traditional Wilson and Jungner criteria have been supplemented by additional criteria, including considerations of equity and access, in response to emerging technologies. This review aims to provide an up-to-date overview of the global landscape of metabolic screening panels, highlight the major ongoing genomic screening projects, and outline the current models for integrating these two screening systems. Substantial differences exist across countries in the numbers and types of diseases included in national NBS programmes. In this context, Italy represents a prominent case, as its neonatal screening framework has seen significant expansion and development in recent years, reaching a particularly comprehensive metabolic screening panel. Nonetheless, a number of initiatives to incorporate genomic technologies into the NBS pathway are currently underway, primarily involving high-income countries. Nonetheless, unlike metabolomic-based NBS programs, no country has a government-mandated NGS program as first-tier testing for newborns. New evidence is emerging from ongoing models of integration of multi-omics approaches into NBS, including the use of AI and machine learning. Identifying the most appropriate system for this integration to reduce the false-positive and false-negative rates associated with both screening types, ensure more equitable access to screening, and facilitate faster access to treatment may represent a useful and foresightful way to conceptualize NBS in the future. This transitional phase should promote rigorous improvements before full-scale adoption. Full article

Crisis events generate massive information flows from diverse sources, which need to be consolidated into public opinion reports to enable timely response by governments and enterprises. Current LLMs, despite strong generation capabilities, fail to achieve perspective diversity, maintain factual consistency, and perform coherent high-level planning. To address these gaps, we propose MPSR: a multi-perspective self-reflection framework. Our framework first assigns diverse stakeholder personas to agents who independently generate initial writing plans from complementary viewpoints. Subsequently, a three-stage debate mechanism refines these plans by identifying conflicts, formulates resolution strategies, and produces a consensus plan, thereby enhancing factual consistency. Finally, we introduce a Report Fusion mechanism to synthesize reports across temporal batches, ensuring comprehensive event coverage. Extensive experiments demonstrate that MPSR significantly outperforms baselines, achieving Date F1 of 0.67, G-Eval of 4.54, and MiniCheck score of 79.43, which represent improvements of 17.5%, 70.0%, and 25.8% over the strongest baseline, respectively. Full article

The Archaic period in the Maya lowlands of Mesoamerica emerged around 8000 BCE and likely lasted until about 1000 BCE; however, both the development and complex cultural adaptations representative of Archaic peoples present challenges for archaeologists. In central Belize, archaeological evidence for Archaic people is limited, especially when compared to northern and southern Belize. Nevertheless, our knowledge of Archaic lifestyles in this part of the world has substantially increased over the last twenty years or so. This paper reviews the current understanding of the Archaic period in central Belize based primarily on radiocarbon dates from stratigraphic excavations, diagnostic lithic artifacts, and both faunal and floral remains recovered from excavations, and compares these data to archaeological evidence from northern and southern Belize for regional contextualization and synthesis. Although some aspects of Archaic lifestyles in central Belize appear quite clear based on the available archaeological evidence, others remain elusive. More regional surveys to find sites and an increased number of excavations with datable stratigraphic contexts are needed to more accurately reconstruct the lives of the people who initially inhabited central Belize prior to the emergence of the first culturally recognizable Maya. Full article

Quantitative real-time PCR (qPCR) remains a cornerstone method for analyzing gene expression due to its high sensitivity, specificity, and reproducibility. However, for reliable results in relative quantification studies, the choice of an appropriate reference gene is critical to ensure accurate normalization. The expression of commonly used reference genes can vary depending on developmental stage and experimental conditions, making their validation essential. To date, no validated reference genes have been reported for Agrostemma githago L. (corn cockle, Caryophyllaceae). To facilitate research on genes involved in natural product biosynthesis and specialized metabolism regulation, we aimed to identify the most stable reference genes across various plant organs and cultivation conditions of this species. Drawing on previous literature, we have selected seven housekeeping genes widely used for evaluation: actin, β-tubulin, elongation factor 1α, glyceraldehyde-3-phosphate dehydrogenase, histone H3, translation elongation factor 1, and eukaryotic translation initiation factor 5A1 (for which two primer sets were tested). The nucleotide sequences of these potential reference genes were identified from the A. githago transcriptome. Using qRT-PCR, transcript levels of seven potential reference genes were estimated in 40 different A. githago samples, including 25 in vitro samples under various treatment conditions and 15 soil-grown samples representing A. githago organs in different developmental stages. Expression stability of candidate reference genes was assessed using the RefFinder platform, which combines four commonly applied statistical algorithms: geNorm, NormFinder, BestKeeper, and the comparative Δ-Ct method. The results revealed that the selection of optimal reference genes varied based on the particular organ, developmental stage and condition being examined. TIF5A1-2 (one of the two primer pairs tested) and GAPHD consistently exhibited the most stable expression under various conditions in vitro. EF1α and H3 exhibited superior performance across different organs of soil-grown plants. Moreover, our integrated analysis enabled the identification of the two most stable, universal reference genes suitable for normalization in A. githago under all tested conditions—H3 and TIF5A1-2. Our work provides a robust foundation for future transcriptomic and functional studies of the specialized metabolism of A. githago and other related species. Full article