Search Results (9,000)

Despite significant progress in preclinical research aimed at developing effective therapies for the acute and long-term consequences of perinatal asphyxia, there is still a lack of clinical protocols to regenerate the neonatal brain damaged by hypoxic-ischemic (HI) injury. To date, only therapeutic hypothermia is routinely used in neonates who have experienced perinatal asphyxia. It has been shown to be effective only in limiting the spread of brain damage caused by a cascade of molecular and biochemical events triggered by limited blood supply to the body’s organs, including the fragile, developing brain. Ongoing clinical trials are exploring pharmacological approaches aimed at promoting neurogenesis and gliogenesis to repair damaged neural tissue, as well as modulating the neuroinflammation that results from the cellular response to HI injury. Among promising therapeutic agents, erythropoietin, and melatonin have emerged as major drugs with potential neuroprotective effects in neonatal hypoxic-ischemic encephalopathy. Erythropoietin is recognized for its anti-apoptotic, anti-oxidative, and anti-inflammatory properties, supporting neural cell survival and regeneration. Melatonin acts as a potent antioxidant and anti-inflammatory agent, helping to reduce oxidative stress and inflammation triggered by HI injury. As clinical trials on suffering neonates are highly demanding, the ethical and practical concerns of therapeutic approaches are discussed. An urgent need to develop a safe, feasible, and effective clinical approach to promote the restoration of appropriate neurodevelopment in the near future is highlighted. This review summarizes the clinical trials conducted to date, discusses their outcomes and limitations, and considers translational potential of the tested treatment strategies. Full article

Skin hyperpigmentation disorders represent a major dermatological challenge, and safe alternatives to conventional depigmenting agents remain scarce. Probiotics and their postbiotic derivatives have emerged as promising natural candidates; however, only a few bacterial strains have been investigated for melanogenesis-inhibitory activity, and their true potential remains largely unexplored. Here, we report for the first time the biosafety profile and anti-melanogenic activity of Lactobacillus salivarius BGHO-1 and Lactobacillus paracasei BGSJ2-8, and assess their possible use in the treatment of skin hyperpigmentation. Two complementary zebrafish-based approaches were employed: (i) image-assisted analysis of pigmentation patterns, melanocyte morphology, and melanocytotoxicity, and (ii) quantitative melanin analysis, enabling integrated safety and efficacy evaluation. We investigated both native and heat-inactivated preparations, including whole cultures, cell-free supernatants, isolated cells, and separated cell walls/membranes and cytoplasmic fractions. While several fractions demonstrated the ability to inhibit melanogenesis, the cell wall/membrane fraction was the most potent, reducing melanin content by 64% compared to untreated embryos, while causing no systemic side effects and preserving melanocyte structure. Furthermore, this fraction did not elicit inflammatory responses or neutropenia, underscoring its favorable safety profile at anti-melanogenic doses. Collectively, this study identifies specific postbiotics as effective and safe modulators of melanogenesis and highlights their translational potential in developing novel approaches for treating skin hyperpigmentation. Full article

Biodegradable polymers such as Polycaprolactone (PCL), Polylactic acid (PLA), and Poly(lactic-co-glycolic acid) (PLGA) are attracting attention as key platforms for anticancer drug delivery systems due to their excellent biocompatibility and controllable degradation rates. These polymers can overcome limitations of existing chemotherapeutics, such as low bioavailability, systemic toxicity, and nonspecific cell damage, and contribute to the development of precision medicine approaches and long-acting therapeutics. This paper discusses the chemical and physicochemical properties of these three polymers, their synthetic strategies, and the controlled drug release technology through surface functionalization and stimuli-responsive design. Furthermore, we highlight their potential for use in various formulations, including micelles, nanoparticles, hydrogels, and microspheres, enabling enhanced drug solubility, sustained release, and tumor targeting. Preclinical and clinical applications demonstrate that these polymer-based DDSs represent a promising approach for implementing next-generation precision anticancer treatment strategies, with further potential for clinical translation and widespread adoption. Full article

Foodborne diseases pose serious risks during pregnancy; however, cross-cultural studies on their cognitive and behavioral factors that influence safe practices are lacking. This study aimed to compare the food safety knowledge, attitudes, and practices (KAPs) of pregnant women in China and Syria and to develop a model that explores how food safety knowledge (FSK) and attitudes (FSAs) influence different practices. A cross-sectional study was conducted among 808 Chinese and 815 Syrian pregnant women using a validated questionnaire. Data were analyzed using descriptive statistics, Chi-square, and Partial Least Squares Structural Equation Modeling. Chinese women demonstrated higher FSK and more positive FSAs (59.0% vs. 48.5%, p = 0.001) than Syrian women, whereas Syrian women showed stronger personal hygiene practices (mean score: 4.06 ± 0.68 vs. 3.93 ± 0.67, p = 0.001). While FSK directly influenced FSAs in both cohorts (China: β = 0.379, p < 0.001; Syria: β = 0.405, p < 0.001), its translation into practices was culturally specific. For Chinese women, FSA fully mediated the relationship between FSK and temperature control (TC) practices (indirect effect: β = 0.121, p < 0.001) and partially mediated personal hygiene and cross-contamination (CC) prevention. In contrast, for Syrian women, FSA mediated the relationship with high-risk food (HRF) avoidance (indirect effect: β = 0.092, p < 0.05) and personal hygiene (indirect β = 0.076, p < 0.05). The findings conclude that the pathways from knowledge to practice are complex and culturally mediated, indicating that effective public health interventions must be tailored to specific socio-cultural contexts to improve food safety behaviors. Full article

This study examines how the integration of structured information affects the performance of large language models (LLMs) in the context of facility management. The aim is to determine to what extent structured data such as maintenance schedules, room information, and asset inventories can improve the accuracy, correctness, and contextual relevance of LLM-generated responses. We focused on scenarios involving function calling of a database with building information. Three use cases were developed to reflect different combinations of structured and unstructured input and output. The research follows a design science methodology and includes the implementation of a modular testing prototype, incorporating empirical experiments using various LLMs (Gemini, Llama, Qwen, and Mistral). The evaluation pipeline consists of three steps: user query translation (natural language into SQL), query execution, and final response (translating the SQL query results into natural language). The evaluation was based on defined criteria such as SQL execution validity, semantic correctness, contextual relevance, and hallucination rate. The study found that the use cases involving function calling are mostly successful. The execution validity improved up to 67% when schema information is provided. Full article

Prostate cancer is the most frequently diagnosed solid-organ malignancy in men worldwide. Metastatic castration-resistant prostate cancer represents a rapidly fatal, end-stage form of the disease for which current therapies remain palliative rather than curative. The advent of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of refractory hematologic malignancies, and a growing number of studies are now exploring its potential in solid tumors. In this review, we first provide a concise overview of current immunotherapeutic strategies for prostate cancer, including checkpoint inhibitors, vaccine-based approaches, and bispecific antibodies. We then focus on the most recent and promising developments in CAR-T cell therapy for this malignancy. Specifically, we examine the key tumor-associated antigens targeted in prostate cancer-directed CAR-T cell therapy and summarize findings from preclinical research as well as ongoing and completed clinical trials. Finally, we discuss the main challenges that limit the efficacy of CAR-T therapy in prostate cancer, such as antigen heterogeneity, immunosuppressive tumor microenvironments, on-target/off-tumor toxicity, limited T-cell persistence, and inefficient trafficking to metastatic lesions, and outline potential strategies to overcome these barriers. Our aim is to define a translational roadmap for advancing CAR-T therapy toward clinical application in patients with metastatic castration-resistant prostate cancer. Full article

This scoping review explores the application of artificial intelligence (AI) methods for analyzing mesenchymal stem cells (MSCs) images. The aim of this study was to identify key areas where AI-based image processing techniques are utilized for MSCs analysis, assess their effectiveness, and highlight existing challenges. A total of 25 studies published between 2014 and 2024 were selected from six databases (PubMed, Dimensions, Scopus, Google Scholar, eLibrary, and Cochrane) for this review. The findings demonstrate that machine learning algorithms outperform traditional methods in terms of accuracy (up to 97.5%), processing speed and noninvasive capabilities. Among AI methods, convolutional neural networks (CNNs) are the most widely employed, accounting for 64% of the studies reviewed. The primary applications of AI in MSCs image analysis include cell classification (20%), segmentation and counting (20%), differentiation assessment (32%), senescence analysis (12%), and other tasks (16%). The advantages of AI methods include automation of image analysis, elimination of subjective biases, and dynamic monitoring of live cells without the need for fixation and staining. However, significant challenges persist, such as the high heterogeneity of the MSCs population, the absence of standardized protocols for AI implementation, and limited availability of annotated datasets. To advance this field, future efforts should focus on developing interpretable and multimodal AI models, creating standardized validation frameworks and open-access datasets, and establishing clear regulatory pathways for clinical translation. Addressing these challenges is crucial for accelerating the adoption of AI in MSCs biomanufacturing and enhancing the efficacy of cell therapies. Full article

This review comprehensively assesses the clinical applications and future potential of alpha-emitting radionuclides available for targeted alpha-particle therapy (TAT) in cancer treatment. The approval of radium-223 therapy in 2013 marked a significant advancement in alpha-emitting therapeutic radiopharmaceuticals, which are primarily used in treatment of prostate cancer. The EU SECURE project was introduced as a major initiative to enhance the sustainability and safety of medical alpha-emitting radionuclides production in Europe. This literature review was conducted by a multidisciplinary team on selected radionuclides, including actinium-225, bismuth-213, astatine-211, lead-212, terbium-149, radium-223 and thorium-227. These were selected based on their clinical significance, as identified in the EU PRISMAP project and subsequent literature searches. The review process involved searching major databases using specific keywords related to alpha-emitter therapy and was limited to articles in English. For each selected radionuclide, the physical characteristics, the radiochemistry, and the pre-clinical and clinical studies are explored. Actinium-225 is the most widely studied alpha emitter, with several preclinical and clinical studies on prostate cancer and neuroendocrine tumours. Other types of tumours (such as glioblastoma) still require preclinical and clinical development. Bismuth-213 bound to antibodies, peptides and nanobodies has shown optimal results in preclinical and clinical studies, with increased median survival and no significant toxicity. Astatine-211 differs from most other α-emitters relevant to TAT, since it yields one α-particle per decay. This offers certain translational advantages, including the simplification of radiation dosimetry calculations and quality control (QC). Lead-212 has the advantage of being an in situ generator with likely widespread availability. Although clinical data are limited, the findings are promising at this stage. The unconventional production of Terbium-149 is the primary reason it has not yet progressed to clinical trials. Overcoming this production obstacle would allow more detailed preclinical investigations. Optimal results with Thorium-227-labelled agents have been observed in preclinical studies, including delays in cellular growth, multiple double-strand breaks and complete regression. Intermediate phase I trial results have also been reported, demonstrating safety and tolerability, as well as an objective response rate of 25%.: The results highlight the advantages of alpha particles in targeting cancer cells with minimal radiation to normal tissue, emphasising the need for high specificity and stability in delivery mechanisms, as well as suggesting that the full clinical potential of alpha particle therapy remains unexplored. Theranostic approach and dosimetric evaluations still represent relevant challenges. Full article

In the context of deep AI–design integration, traditional methods struggle to translate multi-source requirements into sustainable engineering solutions while balancing innovation with practicality. This study proposes AQTA, an intelligent design framework that integrates Analytic Hierarchy Process (AHP), Quality Function Deployment (QFD), Theory of Inventive Problem Solving (TRIZ), and AI-Generated Content (AIGC) to enable sustainable product development. AQTA employs a four-stage closed-loop process: requirement analysis, contradiction resolution, solution generation, and validation. QFD and AHP quantify user and sustainability requirements to identify key contradictions, TRIZ resolves technical conflicts and stimulates innovative solutions, while AIGC generates eco-efficient visual concepts through prompt engineering. Multi-criteria decision-making supports evaluation and optimization based on environmental and economic indicators. Empirical studies demonstrate that AQTA significantly enhances innovation quality, design efficiency, and sustainability performance. The framework provides a replicable, hybrid ‘theory-driven + AI-generated’ methodology, which is validated through the case study of urban fire trucks, contributing to sustainable manufacturing practices in the intelligent era. Full article

The banking sector faces increasing pressure to balance financial performance with sustainability goals amid ongoing digital transformation, regulatory reform, and societal expectations for ethical responsibility. Entrepreneurial leadership has emerged as a pivotal approach for addressing these challenges; however, the behavioral and contextual mechanisms through which it shapes sustainability remain insufficiently understood. Drawing on Social Learning Theory (SLT), this study investigates how and when entrepreneurial leadership enhances sustainable bank performance through the mediating role of employee creativity and the moderating influence of an innovation-oriented climate. A two-wave multi-source survey was conducted among 459 employees and managers from Turkish banks, and the hypothesized model was tested using structural equation modeling to ensure robust empirical validation. The results indicate that entrepreneurial leadership significantly fosters employee creativity, which serves as a critical behavioral mechanism linking leadership behaviors to sustainability-oriented outcomes. Moreover, an innovation-oriented climate strengthens both the direct effect of entrepreneurial leadership on creativity and its indirect effect on sustainable bank performance, emphasizing the contextual importance of supportive organizational environments. Theoretically, this study extends the leadership and sustainability literature by illustrating how learning and behavioral modeling processes translate leadership vision into sustainable performance. Practically, it offers actionable guidance for bank executives to develop innovation-oriented climates, empower employees’ creative engagement, and design incentive systems that align leadership behavior with sustainability imperatives, thereby enhancing resilience and long-term competitiveness. Full article

Peanut (Arachis hypogaea L.) is an important oil and cash crop, but its growth and productivity are severely constrained by low-temperature stress. Growth-regulating factors (GRFs) are plant-specific transcription factors involved in development and stress responses, yet their roles in peanut remain poorly understood. In this study, we identified AhGRF3b as a direct target of ahy-miR396 using degradome sequencing, which demonstrated precise miRNA-mediated cleavage sites within the AhGRF3b transcript. Expression profiling confirmed that ahy-miR396 suppresses AhGRF3b via post-transcriptional cleavage rather than translational repression. Functional analyses showed that overexpression of AhGRF3b in Arabidopsis thaliana promoted leaf expansion by enhancing cell proliferation. Specifically, leaf length, width, and petiole length increased by 104%, 22%, and 28%, respectively (p < 0.05). Under cold stress (0 °C for 7 days), transgenic lines (OE-2 and OE-6) exhibited significantly better growth than Col-0, with fresh weight increased by 158% and 146%, respectively (p < 0.05). Effect size analysis further confirmed these differences (Cohen’s d = 11.6 for OE-2 vs. Col-0; d = 6.3 for OE-6 vs. Col-0). Protein–protein interaction assays, performed using the yeast two-hybrid (Y2H) system and 3D protein–protein docking models, further supported that AhGRF3b interacts with Catalase 1 (AhCAT1), vacuolar cation/proton exchanger 3 (AhCAX3), probable polyamine oxidase 4 (AhPAO4), and ACT domain-containing protein 11 (AhACR11), which are involved in reactive oxygen species (ROS) scavenging and ion homeostasis. These interactions were associated with enhanced CAT and PAO enzymatic activities, reduced ROS accumulation, and upregulation of stress-related genes under cold stress. These findings suggest that the ahy-miR396/AhGRF3b module plays a potential regulatory role in leaf morphogenesis and cold tolerance, providing valuable genetic resources for breeding cold-tolerant peanut varieties. Full article

Although previous research has highlighted the role of environmental concerns, responsibility, knowledge, and social norms in shaping sustainable consumption, the persistence of the intention–action gap remains a key challenge, particularly in Latin America. In this context, this study analyzes the moderating effect of price on the relationship between environmental attitude and its influence on the purchase behavior of organic products in an emerging market setting. To address this issue, a quantitative, cross-sectional survey was conducted with 329 Ecuadorian consumers of organic products, using validated scales adapted from prior studies. The proposed model was tested using partial least squares structural equation Modeling. The results confirm that environmental concern, environmental responsibility, subjective norms, and environmental knowledge positively influence environmental attitudes and that environmental attitude directly affects the purchase behavior of organic products. Importantly, price emerged as a critical moderator, showing that, even when consumers hold favorable environmental attitudes, higher prices significantly constrain their translation into purchasing behavior. This study adds theoretical originality by extending the relationship between environmental attitude and purchase behavior of organic products through the SOR framework and by evidencing in an emerging market context; while EA foster organic purchasing, this relationship is conditioned by the price, a situational factor often overlooked in research from developed economies. Full article

Monkeypox (Mpox) has re-emerged as a global public health threat, with recent outbreaks linked to novel mutations that enhance viral transmissibility and immune evasion. The Mpox virus (MPXV), a double-stranded deoxyribonucleic acid (DNA) orthopoxvirus, shares high structural and enzymatic similarity with the variola virus, underscoring the need for urgent therapeutic interventions. While conventional antiviral development is time-intensive and costly, drug repurposing offers a rapid and cost-effective strategy by leveraging the established safety and pharmacological profiles of existing medications. This is a narrative integrative review synthesizing published evidence on drug repurposing strategies against MPXV. To address these issues, this review explores MPXV molecular targets critical for genome replication, transcription, and viral assembly, highlighting how the Food and Drug Administration (FDA)-approved antivirals (cidofovir, tecovirimat), antibiotics (minocycline, nitroxoline), antimalarials (atovaquone, mefloquine), immunomodulators (infliximab, adalimumab), and chemotherapeutics (doxorubicin) have demonstrated inhibitory activity against the virus using computational or experimental approaches. This review further evaluates advances in computational methodologies that have accelerated the identification of host-directed and viral-directed therapeutic candidates. Nonetheless, translational challenges persist, including pharmacokinetic limitations, toxicity concerns, and the limited efficacy of current antivirals such as tecovirimat in severe Mpox cases. Future research should integrate computational predictions with high-throughput screening, organ-on-chip technologies, and clinical pipelines, while using real-time genomic surveillance to track viral evolution. These strategies establish a scalable and sustainable framework for the MPXV drug discovery. Full article

Antioxidant activity is a normal physiological function that is essential for healthy living, and it is maintained by antioxidant dietary nutrients. However, increases in free radical production and oxidative toxicity in many clinical conditions can cause serious and sometimes irreversible damage. Despite many investigations, including hundreds of clinical trials suggesting that there are health benefits obtained from the use of natural antioxidants, no antioxidant drugs have yet been developed for the treatment of any disease associated with free radical pathology. Millions of people choose to use nutraceutical and natural product antioxidants as therapeutics and also for chemoprevention against cancer and other diseases. New academic efforts and strategies are required for the development of antioxidant drugs in clinical practice in the absence of interest by the pharmaceutical and nutraceutical industries. One of the most effective antioxidant therapeutic strategies is inhibition by chelators of iron involved in the catalytic formation of free radical reactions and their associated damage. Hundreds of phytochelators have been shown to inhibit oxidative damage, similar to the iron-chelating drugs deferiprone and deferoxamine. In particular, several nutraceuticals and natural products such as ascorbic acid, quercetin, curcumin, fisetin, lipoic acid, and maltol have been shown to have high antioxidant activity and iron-binding capacity, as well as other effects on iron metabolism, in pre-clinical studies and clinical trials involving different categories of patients. For example, ascorbic acid and maltol–iron complexes are sold as pharmaceutical products for the treatment of iron deficiency. The development of nutraceuticals as antioxidant drugs may involve one or more applications, such as short- or long-term treatments, single-drug or combination therapies, and also different targets, such as the prevention, treatment, or post-treatment of diseases associated with free radical pathology as well as ferroptosis. The academic efforts surrounding the developments of iron-chelating nutraceuticals or natural products into antioxidant pharmaceuticals should fulfill all of the regulatory requirements and include clinical tests of antioxidants in rare or untreatable diseases, as well as the involvement of government translational research institutions and expert groups that specialize in regulatory drug affairs, among others. Full article

(1) Patients in a minimally conscious state (MCS) and their families face prolonged emotional distress and psychological challenges due to the uncertainty of recovery and limited means of emotional communication. This study aims to develop an EEG-based emotion visualization system to support affected families by translating patients’ neural activity into perceivable emotional imagery. (2) Using simulated MCS patient EEG data corresponding to different emotional states, we designed a dynamic visual interface via TouchDesigner to convert bio-signals into real-time emotional animations. User tests involving questionnaires and interviews were conducted to evaluate the system’s performance. (3) The results demonstrate that the system accurately conveys emotional states, enhances caregivers’ perception of patients’ internal conditions, and significantly alleviates family members’ anxiety. (4) These findings suggest that EEG-based emotion visualization offers a viable and compassionate tool for supporting MCS families, providing new pathways for interdisciplinary research combining neuroscience and design while establishing a foundation for future clinical and home-care applications. Full article