Search Results (830)

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

Adipose stem cells (ASCs) are a subset of mesenchymal stem cells with validated immunomodulatory and regenerative capabilities that make them attractive tools for treating neurodegenerative disorders, such as multiple sclerosis (MS). Several studies conducted on experimental autoimmune encephalomyelitis (EAE), the animal model of MS, have clearly shown a therapeutic effect of ASCs. However, controversial data on their efficacy were obtained from I- and II-phase clinical trials in MS patients, highlighting standardization issues and limited data on long-term safety. In this context, ASC-derived extracellular vesicles from (ASC-EVs) represent a safer, more reproducible alternative for EAE and MS treatment. Moreover, their physical characteristics lend themselves to a non-invasive, efficient, and easy handling of intranasal delivery. Using an in vitro setting, we first verified ASC-EVs’ ability to cross the human nasal epithelium under an inflammatory milieu. Magnetic resonance corroborated these data in vivo in intranasally treated MOG35-55-induced EAE mice, showing a preferential accumulation of ASC-EVs in brain-inflamed lesions compared to a stochastic distribution in healthy control mice. Moreover, intranasal treatment of ASC-EVs at the EAE onset led to a long-term therapeutic effect using two different experimental protocols. A marked reduction in T cell infiltration, demyelination, axonal damage, and cytokine production were correlated to EAE amelioration in ASC-EV-treated mice compared to control mice, highlighting the immunomodulatory and neuroprotective roles exerted by ASC-EVs during EAE progression. Overall, our study paves the way for promising clinical applications of self-administered ASC-EV intranasal treatment in CNS disorders, including MS. Full article

Ammonia (NH₃) emissions affect the environment, climate and human health and originate mainly from agricultural sources like synthetic nitrogen fertilizers. Accurate and replicable measurements of NH₃ emissions are crucial for research, inventories and evaluation of mitigation measures. There exist specific application limitations of NH₃ emission measurement techniques and a high variability in method performance between studies, in particular from small plots. Therefore, the aim of this study was the assessment of measurement methods for ammonia emissions from replicated small plots. Methods were evaluated in 18 trials on six sites in Germany (2021–2022). Urea was applied to winter wheat as an emission source. Two small-plot methods were employed: inverse dispersion modelling (IDM) with atmospheric concentrations obtained from Alpha samplers and the dynamic chamber Dräger tube method (DTM). Cumulative NH₃ losses assessed by each method were compared to the results of the integrated horizontal flux (IHF) method using Alpha samplers (Alpha IHF) as a micrometeorological reference method applied in parallel large-plot trials. For validation, Alpha IHF was also compared to IHF/ZINST with Leuning passive samplers. Cumulative NH₃ emissions assessed using Alpha IHF and DTM showed good agreement, with a relative root mean square error (rRMSE) of 11%. Cumulative emissions assessed by Leuning IHF/ZINST deviated from Alpha IHF, with an rRMSE of 21%. For low-wind-speed and high-temperature conditions, NH₃ losses detected with Alpha IDM had to be corrected to give acceptable agreement (rRMSE 20%, MBE +2 kg N ha⁻¹). The study shows that quantification of NH₃ emissions from small plots is feasible. Since DTM is constrained to specific conditions, we recommend Alpha IDM, but the approach needs further development. Full article

Objectives: Sialic acid (SA), a naturally occurring compound abundantly found in birds’ nests, holds immense promise for skincare applications owing to its remarkable biological properties. However, its low bioavailability, poor stability, and limited skin permeability have constrained its widespread application. Methods: To overcome these challenges, SA was encapsulated within nanoliposomes (NLPs) by the high-pressure homogenization technique to develop an advanced and efficient transdermal drug delivery system. The skincare capabilities of this novel system were comprehensively evaluated across multiple experimental platforms, including in vitro cell assays, 3D skin models, in vivo zebrafish studies, and clinical human trials. Results: The SA-loaded NLPs (SA-NLPs) substantially improved the transdermal penetration and retention of SA, facilitating enhanced cellular uptake and cell proliferation. Compared to free SA, SA-NLPs demonstrated a 246.98% increase in skin retention and 1.8-fold greater cellular uptake in HDF cells. Moreover, SA-NLPs protected cells from oxidative stress-induced damage, stimulated collagen synthesis, and effectively suppressed the secretion of matrix metalloproteinases, tyrosinase activity, and melanin production. Additionally, zebrafish-based assays provided in vivo evidence of the skincare efficacy of SA-NLPs. Notably, clinical evaluations demonstrated that a 56-day application of the SA-NLPs-containing cream resulted in a 4.20% increase in L*, 7.87% decrease in b*, 8.45% decrease in TEWL, and 4.01% reduction in wrinkle length, indicating its superior brightening, barrier-repair, and anti-aging effects. Conclusions: This multi-level, systematic investigation strongly suggests that SA-NLPs represent a highly promising transdermal delivery strategy, capable of significantly enhancing the anti-aging, barrier-repair, and skin-brightening properties of SA, thus opening new avenues for its application in the fields of dermatology and cosmeceuticals. Full article

This systematic review aimed to evaluate the effectiveness of teriparatide (TP) in guided bone regeneration (GBR). An electronic search without language or date restrictions was performed in PubMed, Web of Science, Scopus, Scielo, and gray literature for articles published until June 2025. Inclusion criteria considered studies evaluating the effect of TP on bone regeneration, analyzed using SYRCLE’s Risk of Bias tool. Twenty-four preclinical studies were included, covering diverse craniofacial models (mandibular, calvarial, extraction sockets, sinus augmentation, distraction osteogenesis, segmental defects) and employing systemic or local TP administration. Teriparatide consistently enhanced osteogenesis, graft integration, angiogenesis, and mineralization, with potentiated effects when combined with various biomaterials, including polyethylene glycol (PEG), hydroxyapatite/tricalcium phosphate (HA/TCP), biphasic calcium phosphate (BCP), octacalcium phosphate collagen (OCP/Col), enamel matrix derivatives (EMDs), autografts, allografts, xenografts (Bio-Oss), strontium ranelate, and bioactive glass. Critically, most studies presented a moderate-to-high risk of bias, with insufficient randomization, allocation concealment, and blinding, which limited the internal validity of the findings. TP shows promising osteoanabolic potential in guided bone regeneration, enhancing bone formation, angiogenesis, and scaffold integration across preclinical models. Nonetheless, its translation to clinical practice requires well-designed human randomized controlled trials to define optimal dosing strategies, long-term safety, and its role in oral and craniomaxillofacial surgical applications. Full article

Dioscorea species, known as “Yams”, belong to the Dioscoreaceae family. Members of the Dioscoreaceae family are widely distributed across subtropical and tropical regions. They are notable for their high content of starch, dietary fiber, and various bioactive compounds. In addition to serving as a staple food source, these tubers possess significant medicinal value in traditional medicine, particularly for treating diabetes, diarrhea, and various inflammatory diseases. This study aimed to comprehensively summarize the active components and food development potential of Dioscorea species from research over the past decade by searching commonly used databases such as PubMed, Web of Science, Scopus, and Google Scholar. This review highlights the classification of bioactive compounds in Dioscorea spp. using the NPClassifier tool. We discuss 60 representative bioactive metabolites, including terpenoids, phenylpropanoids, carbohydrates, fatty acids, alkaloids, and amino acids. Additionally, we discuss the functional food applications and regulations of Dioscorea spp., which possess antioxidant, anti-inflammatory, anti-diabetic, and anticancer properties. This review is expected to provide scientific ideas for future research related to prioritizing the optimization of extraction technologies, the execution of rigorous clinical trials to confirm therapeutic effects, and the exploration of novel applications of Dioscorea spp. bioactives to fully harness their potential in improving human health. Full article

Ancient grains, including wild rice, millet, fonio, teff, quinoa, amaranth, and sorghum, are re-emerging as vital components of modern diets due to their dense nutritional profiles and diverse health-promoting bioactive compounds. Rich in high-quality proteins, dietary fiber, essential micronutrients, and a broad spectrum of bioactive compounds such as phenolic acids, flavonoids, carotenoids, phytosterols, and betalains, these grains exhibit antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and immunomodulatory properties. Their health-promoting effects are underpinned by multiple interconnected mechanisms, including the reduction in oxidative stress, modulation of inflammatory pathways, regulation of glucose and lipid metabolism, support for mitochondrial function, and enhancement of gut microbiota composition. This review provides a comprehensive synthesis of the essential nutrients, phytochemicals, and functional properties of ancient grains, with particular emphasis on the nutritional and molecular mechanisms through which they contribute to the prevention and management of chronic diseases such as cardiovascular disease, type 2 diabetes, obesity, and metabolic syndrome. Additionally, it highlights the growing application of ancient grains in functional foods and nutrition-sensitive dietary strategies, alongside the technological, agronomic, and consumer-related challenges limiting their broader adoption. Future research priorities include well-designed human clinical trials, standardization of compositional data, innovations in processing for nutrient retention, and sustainable cultivation to fully harness the health, environmental, and cultural benefits of ancient grains within global food systems. Full article

The growing global demand for energy has resulted in a demand for innovative strategies for residential energy management. This study explores a novel framework—MELISSA (Modern Energy LLM-IoE Smart Solution for Automation)—that integrates Internet of Things (IoT) sensor networks with Large Language Models (LLMs) to optimize household energy consumption through intelligent automation and personalized interactions. The system combines real-time monitoring, machine learning algorithms for behavioral analysis, and natural language processing to deliver personalized, actionable recommendations through a conversational interface. A 12-month randomized controlled trial was conducted with 100 households, which were stratified across four socioeconomic quintiles in metropolitan areas. The experimental design included the continuous collection of IoT data. Baseline energy consumption was measured and compared with post-intervention usage to assess system impact. Statistical analyses included k-means clustering, multiple linear regression, and paired t-tests. The system achieved its intended goal, with a statistically significant reduction of 5.66% in energy consumption (95% CI: 5.21–6.11%, $p<0.001$) relative to baseline, alongside high user satisfaction (mean = 7.81, SD = 1.24). Clustering analysis ($k=4$, silhouette = 0.68) revealed four distinct energy-consumption profiles. Multiple regression analysis ($R^2=0.68$, $p<0.001$) identified household size, ambient temperature, and frequency of user engagement as the principal determinants of consumption. This research advances the theoretical understanding of human–AI interaction in energy management and provides robust empirical evidence of the effectiveness of LLM-mediated behavioral interventions. The findings underscore the potential of conversational AI applications in smart homes and have practical implications for optimization of residential energy use. Full article

Diabetic foot ulcers (DFUs) represent a critical global health issue, necessitating the development of advanced smart, flexible, and wearable sensors for continuous monitoring that are reimbursable within foot orthotics. This study presents the design and characterization of a pressure sensor implemented into a shoe insole to monitor diabetic wound pressures, emphasizing the need for a high sensitivity, durability under cyclic mechanical loading, and a rapid response time. This investigation focuses on the electrical and mechanical properties of carbon nanotube (CNT) composites utilizing Ecoflex and polydimethylsiloxane (PDMS). Morphological characterization was conducted using Transmission Electron Microscopy (TEM), Laser Confocal Microscopy, and Scanning Electron Microscopy (SEM). The electrical and mechanical properties of the CNT/Ecoflex- and the CNT/PDMS-based sensor composites were then investigated. CNT/Ecoflex was then further evaluated due to its lower variability performance between cycles at the same pressure, as well as its consistently higher capacitance values across all trials in comparison to CNT/PDMS. The CNT/Ecoflex composite sensor showed a high sensitivity (2.38 to 3.40 kPa⁻¹) over a pressure sensing range of 0 to 68.95 kPa. The sensor’s stability was further assessed under applied pressures simulating human weight. A custom insole prototype, incorporating 12 CNT/Ecoflex elastomeric matrix-based sensors (as an example) distributed across the metatarsal heads, midfoot, and heel regions, was developed and characterized. Capacitance measurements, ranging from 0.25 pF to 60 pF, were obtained across N = 3 feasibility trials, demonstrating the sensor’s response to varying pressure conditions linked to different body weights. These results highlight the potential of this flexible insole prototype for precise and real-time plantar surface monitoring, offering an approachable avenue for a challenging diabetic orthotics application. Full article

Mitochondria are currently of great interest to scientists. The role of mitochondrial DNA (mtDNA) mutations has been proven in the genesis of more than 200 pathologies, which are called mitochondrial disorders. Therefore, the study of mitochondria and mitochondrial DNA is of great interest not only for understanding cell biology but also for the treatment and prevention of many mitochondria-related pathologies. There are two main trends of mitochondrial therapy: mitochondrial replacement therapy (MRT) and mitochondrial transplantation therapy (MTT). Also, there are two main categories of MRT based on the source of mitochondria. The heterologous approach includes the following methods: pronuclear transfer technique (PNT), maternal spindle transfer (MST), Polar body genome transfer (PBT) and germinal vesicle transfer (GVT). An alternative approach is the autologous method. One promising autologous technique was the autologous germline mitochondrial energy transfer (AUGMENT), which involved isolating oogonial precursor cells from the patient, extracting their mitochondria, and then injecting them during ICSI. Transmission of defective mtDNA to the next generation can also be prevented by using these approaches. The development of a healthy child, free from genetic disorders, and the prevention of the occurrence of lethal mitochondrial disorders are the main tasks of this method. However, a number of moral, social, and cultural objections have restricted its exploration, since humanity first encountered the appearance of a three-parent baby. Therefore, this review summarizes the causes of mitochondrial diseases, the various methods involved in MRT and the results of their application. In addition, a new technology, mitochondrial transplantation therapy (MTT), is currently being actively studied. MTT is an innovative approach that involves the introduction of healthy mitochondria into damaged tissues, leading to the replacement of defective mitochondria and the restoration of their function. This technology is being actively studied in animals, but there are also reports of its use in humans. A bibliographic review in PubMed and Web of Science databases and a search for relevant clinical trials and news articles were performed. A total of 81 publications were selected for analysis. Methods of MRT procedures were reviewed, their risks described, and the results of their use presented. Results of animal studies of the MTT procedure and attempts to apply this therapy in humans were reviewed. MRT is an effective way to minimize the risk of transmission of mtDNA-related diseases, but it does not eliminate it completely. There is a need for global legal regulation of MRT. MTT is a new and promising method of treating damaged tissues by injecting the body’s own mitochondria. The considered methods are extremely good in theory, but their clinical application in humans and the success of such therapy remain a question for further study. Full article

This review provides a comprehensive analysis of recent advancements in lower limb exoskeleton systems, focusing on applications, control strategies, hardware architecture, sensing modalities, human-robot interaction, evaluation methods, and technical innovations. The study spans systems developed for gait rehabilitation, mobility assistance, terrain adaptation, pediatric use, and industrial support. Applications range from sit-to-stand transitions and post-stroke therapy to balance support and real-world navigation. Control approaches vary from traditional impedance and fuzzy logic models to advanced data-driven frameworks, including reinforcement learning, recurrent neural networks, and digital twin-based optimization. These controllers support personalized and adaptive interaction, enabling real-time intent recognition, torque modulation, and gait phase synchronization across different users and tasks. Hardware platforms include powered multi-degree-of-freedom exoskeletons, passive assistive devices, compliant joint systems, and pediatric-specific configurations. Innovations in actuator design, modular architecture, and lightweight materials support increased usability and energy efficiency. Sensor systems integrate EMG, EEG, IMU, vision, and force feedback, supporting multimodal perception for motion prediction, terrain classification, and user monitoring. Human–robot interaction strategies emphasize safe, intuitive, and cooperative engagement. Controllers are increasingly user-specific, leveraging biosignals and gait metrics to tailor assistance. Evaluation methodologies include simulation, phantom testing, and human–subject trials across clinical and real-world environments, with performance measured through joint tracking accuracy, stability indices, and functional mobility scores. Overall, the review highlights the field’s evolution toward intelligent, adaptable, and user-centered systems, offering promising solutions for rehabilitation, mobility enhancement, and assistive autonomy in diverse populations. Following a detailed review of current developments, strategic recommendations are made to enhance and evolve existing exoskeleton technologies. Full article

Cyclophosphamide (CPX) is an alkylating agent commonly used for various hematological and solid malignancies. In addition to its use as a cytotoxic agent to directly kill tumor cells, numerous immunomodulatory properties of CPX in the tumor microenvironment (TME) of several cancer types have also been documented. These properties include the selective depletion of immune-suppressive regulatory T cells (Tregs), triggering of immunogenic cell death (ICD) and enhanced antigen presentation, and release of type I interferons (IFNs). Moreover, preclinical models as well as human clinical trials have investigated the efficacy of the low-dose “metronomic” scheduling of CPX in combination with immunotherapies such as immune checkpoint inhibitors, dendritic cell tumor vaccines, and tumor antigen peptide vaccines. The metronomic dosing schedule involves administering a continuous (or frequent, such as daily) low dose of chemotherapy rather than using the canonical approach of administering the maximum tolerated dose. Despite the approval of immune checkpoint inhibitors for clinical usage against an increasing number of cancers, many malignancies simply do not respond to checkpoint inhibition, in part due to the heterogeneous intratumoral network of immune-suppressive cell populations. The immunomodulatory effects of cyclophosphamide have strong translational applicability and could serve to enhance and bolster anti-tumor immunity, potentially synergizing with immune checkpoint inhibitors and other existing immunotherapy agents. Full article

Thyroid eye disease (TED) is a complex autoimmune disorder characterized by orbital inflammation and tissue remodeling. Teprotumumab, a fully human monoclonal antibody targeting insulin-like growth factor-1 receptor (IGF-1R), represents a significant breakthrough in TED treatment. This review comprehensively analyzes the therapeutic role of teprotumumab in TED management. Mechanistically, teprotumumab inhibits the IGF-1R/TSHR signaling complex, thereby reducing orbital fibroblast differentiation and inflammatory responses. Phase II and III clinical trials have demonstrated its remarkable efficacy in reducing proptosis and improving clinical activity scores, with the benefits extending to both active and chronic TED cases. Real-world studies have validated these findings further and expanded its potential applications to various clinical scenarios, including dysthyroid optic neuropathy and steroid-resistant cases. However, several challenges remain. These include treatment-related adverse effects such as hyperglycemia and hearing impairment, with emerging evidence suggesting ethnic variations in susceptibility. The high cost of treatment poses significant accessibility barriers, while limited long-term follow-up data and potential disease recurrence necessitate further investigation. This review synthesizes the current evidence to inform clinical decision-making and highlights areas requiring additional research to optimize teprotumumab’s therapeutic application in TED management. Full article

Background: A comparative analysis was conducted between two immunisation protocols using different amounts of protein extracts from adult Haemonchus contortus worms, purified by thiol-Sepharose chromatography (625 μg/animal vs. 200 μg/animal). These protocols involved either five or two inoculations of the immunogen, respectively. Methods: To evaluate the level of immunoprotection, animals were challenged with L3 of H. contortus two weeks after the last inoculation of the immunogen and humanely sacrificed at 8 weeks post-infection. Parasitological, biopathological, and serological parameters were monitored through the experiment. Parasite burden, abomasal-specific antibody responses, and histopathological changes were determined at the end of the trial. Results: The immunisation protocols resulted in similar reductions in cumulative faecal egg counts (60.5–64.9%) and the total worm burden (47.5–50%) compared to non-immunized (control) animals. Overall, these parasitological data showed an early recovery of the haematocrit (PCV) after challenge in the immunised groups relative to control. Similarly, levels of H. contortus-specific IgG and IgA antibodies increased in both the serum and gastric mucus of immunised groups. Conclusions: These findings represent a further step towards the potential application of this type of immunogen under field conditions, as protective responses (associated with a reduction in faecal egg output) were achieved using a simplified protocol, with lower immunogen doses and fewer inoculations required to induce immunoprotection, thereby mitigating the pathological effects of the parasite and reducing its ability to spread and infect susceptible hosts. Full article

Cartilage injuries, due to their limited regenerative capacity, often result in chronic pain and functional impairment. These injuries are difficult to manage with conventional surgical repair techniques; therefore, alternative treatments are necessary. Gelatin methacrylate (GelMA) has emerged as a promising biomaterial for cartilage tissue engineering due to its biocompatibility, tunable mechanical properties, and ability to be used in advanced applications like 3D bioprinting. This review examines the synthesis, properties, and limitations of GelMA in cartilage repair, focusing on its applications in 3D bioprinting for the creation of patient-specific cartilage constructs. It also highlights preclinical studies exploring the potential of GelMA-based scaffolds in various animal models. Despite its advantages, challenges remain, such as the mechanical limitations of GelMA and its degradation rate in dynamic environments. Hybrid scaffolds, in situ bioprinting, and personalized bioinks offer solutions to these issues. Ultimately, long-term clinical trials are needed to assess the durability and efficacy of GelMA-based scaffolds in human applications. Future research is aimed at overcoming these challenges, improving the mechanical strength of GelMA scaffolds, and enhancing their clinical translation for cartilage repair. Full article