Search Results (1,623)

This study investigates the influence of PLA flowability and talc content on the performance of compostable thermoplastic starch/poly(butylene succinate) (TPS/PBS)-based systems for rigid applications. Different PLA grades with varying melt flow index (PLA23, PLA8 and PLA70) and talc contents (0, 5 and 10 wt%) were incorporated. Twelve formulations were compounded by twin-screw extrusion and processed by injection moulding. FTIR confirmed the coexistence of TPS, PBS and PLA phases without evidence of chemical interactions. Morphological analysis showed that PLA flowability plays a key role in phase distribution, with higher-flow PLA promoting improved dispersion and interfacial adhesion, while talc addition (5 and 10 wt%) increased structural heterogeneity; at higher loadings, particularly, DSC analysis revealed that talc acted as a nucleating agent for the PBS phase, increasing crystallisation temperatures from approximately 73 °C to 81 °C depending on formulation. Mechanical results showed that Young’s modulus increased from approximately 1.4 GPa to 2.7 GPa with decreasing PLA flowability and increasing talc content. Formulations containing low-flow PLA reached tensile strengths close to 32 MPa, although elongation at break decreased to values near 2%. In contrast, high-flow PLA formulations exhibited a more balanced mechanical response, with elongation values up to approximately 8%, associated with improved phase dispersion. Hybrid PLA systems showed intermediate behaviour, reaching elongations up to 22% while maintaining modulus values around 1.8 GPa. Talc provided additional reinforcement but reduced deformation capacity. HDT values remained relatively constant, indicating limited improvement in thermomechanical resistance despite increased stiffness. These results demonstrate that the combined control of PLA molecular characteristics and talc content enables tuning of the mechanical and thermomechanical performance of TPS/PBS/PLA/talc systems for rigid packaging applications. Full article

Background/Objectives: Stevia rebaudiosides represent a class of compounds extracted from the Stevia rebaudiana Bertoni plant or produced via yeast fermentation, which provide a sweet taste with little to no calories. These compounds are commercially referred to as stevia and are used in the food industry to reduce sugar in foods and beverages. Stevia is a non-nutritive sweetener (NNS), which is a class of ingredients which represent both artificial and plant-based sweeteners. NNSs are widely used and have been well studied. However, their effects on efficacy for weight management as a sugar reduction tool and overall metabolic effects are inconsistent. Of the approved NNSs for use, stevia is relatively new and one of the least studied. However, recent human clinical research has provided insights into stevia’s metabolic effects, effects on the gut microbiome and effects on weight management when used to replace sugar. The objective of this narrative review of human clinical studies is to provide an overview of the effects of stevia rebaudiosides (largely rebaudioside A) on glucoregulatory and cardiometabolic functions, as well as their effects on gut microbiome and weight management. These studies were typically short term (acute to three months) and heterogeneous by design, and they contained stevia rebaudiosides as lone sweeteners and as part of a binary blend with other NNSs. The majority of metabolic studies on stevia rebaudiosides have evaluated the effects on glucose homeostasis and, to a lesser extent, the effects on cardiometabolic function, the gut microbiome, and weight management. These studies suggest that stevia rebaudiosides have no statistically significant effects on glycemia, insulinemia, blood lipids, appetite hormones, or the gut microbiome. Limited studies suggest that, particularly when compared to sucrose, stevia produces very modest body weight and BMI changes, while studies on subjective appetite and food intake have had inconsistent results. Conclusions: longer-term studies are needed, with more consistent and rigorous design protocols across various populations. However, current human clinical studies suggest that stevia rebaudiosides have a limited impact on metabolic functions, and the observed effects on gut microbiome and changes in body weight, particularly when used to replace sugar, warrant further study. Full article

Alpha-1 antitrypsin deficiency (AATD) is a genetically heterogeneous disorder with well-established pulmonary and hepatic manifestations; however, the clinical significance of rare compound heterozygous SERPINA1 variants remains incompletely defined. We report the case of a 61-year-old never-smoking woman with chronically elevated liver transaminase who was found to carry a compound heterozygous SERPINA1 genotype (PI*V/M_procida) previously classified as non-polymerogenic and not previously associated with hepatic inclusions. This case expands the phenotypic spectrum of AATD and highlights the importance of considering SERPINA1 genotyping in adults with unexplained chronic transaminase elevation, while raising clinically relevant questions regarding surveillance and management in atypical AATD phenotypes. Full article

The thyroid gland is particularly vulnerable to the effects of environmental pollutants, due to its high vascularization, dependence on iodine uptake, and intrinsic oxidative environment required for hormone biosynthesis. Therefore, environmental exposure to heavy metals (HMs) and endocrine-disrupting chemicals (EDCs) has emerged as a potential contributor to thyroid dysfunction and carcinogenesis. Despite increasing interest, the clinical relevance of these exposures remains incompletely defined. Available epidemiological data suggest heterogeneous associations across EDCs and HMs classes. While evidence is more consistent for some pollutants, for other compounds it remains limited. Furthermore, while experimental studies provide strong mechanistic support for the key pathways linking environmental exposure to thyroid dysfunction and carcinogenesis, the clinical interpretation of epidemiological data is constrained by important methodological limitations. This narrative review aims to integrate current epidemiological and experimental evidence on the role of HMs and EDCs in thyroid diseases, including both non-neoplastic disorders and thyroid cancer, examining their environmental distribution, exposure pathways, and biological effects. Full article

Glioblastoma (GB) is the most aggressive primary central nervous system tumor in adults and the most common malignant primary brain tumor, representing approximately 50.9% of all malignant CNS tumors, with a median overall survival of approximately 14.6 months despite standard multimodal treatment, consisting of surgical resection, concurrent radiotherapy, and temozolomide (TMZ), followed by adjuvant TMZ (Stupp protocol). Tumor recurrence is inevitable and attributed to diffuse infiltration of neoplastic cells into the brain parenchyma, marked intratumoral heterogeneity, the presence of glioma stem cells, and the protection conferred by the BBB. Flavonoids are plant-derived polyphenolic compounds with more than 8000 identified. They have attracted growing interest as potential therapeutic agents because of their capacity to modulate multiple oncogenic signaling pathways and their favorable toxicity profile. Here we synthesize the preclinical evidence on the main flavonoids with documented activity in GB models, with emphasis on quercetin, apigenin, luteolin, and EGCG, while distinguishing glioblastoma-specific evidence from indirect findings derived from other experimental systems. We analyze their underlying molecular mechanisms, including induction of apoptosis through the intrinsic and extrinsic pathways, inhibition of cell proliferation and angiogenesis, suppression of migration and invasion, epigenetic modulation, and, particularly, the capacity to target the glioma stem cell population. We also examine the limited oral bioavailability and restricted penetration across the BBB, as these factors remain major barriers to translational development. We conclude with an analysis of emerging nanotechnological strategies, targeted delivery systems, and synergistic combinations with conventional chemotherapeutic agents, together with a cautious assessment of the current clinical evidence, which remains insufficient to support the use of flavonoids outside controlled clinical trials. Full article

Per- and polyfluoroalkyl substances (PFASs) present a critical challenge to global public health and environmental integrity due to the exceptional stability of the carbon–fluorine (C–F) bond. This review synthesizes current knowledge on PFAS physicochemical properties, exposure pathways, and toxicological outcomes, while evaluating global regulatory efficacy. A central problem addressed in this review is the widening discrepancy between rigid, yet deeply fragmented, international regulatory frameworks and the increasingly complex, non-linear epidemiological data regarding PFAS health risks. While historical paradigms focused heavily on direct carcinogenicity, recent high-resolution data reveal significant heterogeneity and methodological inconsistencies in cancer links. Instead, robust evidence points to severe systemic toxicities—including hepatotoxicity, immunotoxicity, and maternal–fetal disruptions—frequently driven by mixture co-exposures and sex-specific metabolic dimorphisms. Furthermore, the industrial transition to short-chain substitutes has inadvertently compounded the crisis due to their high environmental mobility and resistance to conventional water treatment. By critically evaluating these toxicological and regulatory contradictions, this review demonstrates that current substance-by-substance legislative models fail to mitigate real-world pollution trends. Ultimately, we emphasize the urgent need to transition to holistic mixture modeling, implement unified class-based global regulations, and accelerate advanced destructive remediation technologies to mineralize the resilient C–F bond. Full article

Background: 5-(3′,4′-Dihydroxyphenyl)-γ-valerolactone (DHPV) is a postbiotic gut microbiota-derived flavanol metabolite with reported anti-inflammatory activity. Despite growing interest in its potential dermatological applications, its pharmaceutical properties and suitability for topical delivery have not been systematically investigated. This study aimed to perform the first comprehensive preformulation and formulation-oriented evaluation of DHPV and to develop stable topical ointment formulations suitable for further dermatological research. Methods: The physicochemical properties of DHPV were characterized using powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), quantitative solubility assessment, and excipient compatibility studies. Based on the obtained preformulation data, two anhydrous ointment formulations containing DHPV were developed. The formulations were evaluated for homogeneity, rheological behavior, chemical stability under accelerated storage conditions, and in vitro drug release performance. Results: DHPV was identified as a crystalline compound with heterogeneous particle morphology and limited aqueous solubility. Quantitative solubility studies demonstrated the highest solubility in PEG 300 and glycol-based solvents. Compatibility testing revealed increased impurity formation in hydrophilic environments, whereas lipophilic excipients provided improved chemical stability. Both ointment formulations exhibited acceptable physical characteristics and maintained DHPV stability throughout accelerated storage. However, marked differences in release behavior were observed. The lipid–wax formulation showed significantly higher release rates, lower variability, and more reproducible release profiles than the petrolatum-based reference formulation, indicating more efficient diffusion of DHPV from the semisolid matrix. Conclusions: The physicochemical characteristics of DHPV strongly influence formulation design and performance. Anhydrous lipid-based systems provide a favorable environment for maintaining DHPV stability, while formulation composition significantly affects drug release. The developed lipid–wax formulation represents a promising platform for future skin permeation, pharmacodynamic, and efficacy studies. Full article

Rosa damascena Mill. is a medicinal and aromatic species of major pharmacological and economic importance, widely valued for its complex profile of bioactive secondary metabolites. While extensive research has focused on field-grown plants and essential oils, comparatively little attention has been devoted to the behavior of R. damascena under in vitro conditions. Plant tissue culture systems provide controlled platforms for investigating secondary metabolism independently of environmental variability; however, their application to R. damascena has produced heterogeneous and often inconsistent results. This review examines the main in vitro culture systems developed for R. damascena, including callus, suspension, and organ-derived cultures, with emphasis on their capacity to accumulate secondary metabolites. Available evidence indicates that undifferentiated cultures generally fail to reproduce the full metabolic complexity observed in planta, particularly for volatile monoterpenes associated with tissue specialization. Nevertheless, several studies demonstrate that in vitro systems can accumulate phenolic compounds with relevant biological activities, supporting their use as experimental models for investigating metabolic regulation. By integrating early studies with recent advances in plant biotechnology, this review highlights current limitations, unresolved questions, and future perspectives for the use of R. damascena in vitro cultures in medicinal plant research. Full article

Background: Uveal melanoma is the most common intraocular malignancy in adults with a poor prognosis. Although local therapies are effective, treatment options for advanced disease remain limited. Combination strategies using chemotherapeutic agents and natural compounds, such as quercetin, are in focus for their potential to enhance antitumor efficiency and overcome resistance. Methods: The effects of doxorubicin, quercetin, and their combination were investigated in uveal melanoma cell lines. Cell viability was determined by an MTT assay, and apoptosis and cell cycle distribution by flow cytometry. Invasion assays were performed to evaluate metastatic potential, while modifications in signaling pathways were analyzed by Western blotting and qPCR. Results: Both doxorubicin and quercetin significantly reduced cell viability and induced apoptotic and necrotic cell death. The combination treatment demonstrated additional inhibitory effects in both cell lines, shown by increased SubG1 populations, reduced invasive capacity, and modulation of signaling pathways. Cell cycle analysis indicated treatment-induced growth inhibition. Notably, pathway modifications varied between cell lines, suggesting heterogeneous responses. Conclusions: Quercetin may potentiate certain antitumor effects of doxorubicin in uveal melanoma, particularly by reducing post-treatment invasiveness and modulating certain PI3K/AKT pathway-related proteins. These results support the possibility of quercetin-based combination therapies, although further molecular and in vivo studies are required. Full article

Agri-food byproducts are increasingly recognized as sustainable feedstocks for high-value bioactive compounds; but their practical valorization requires integrated evidence on recovery conditions; chemical composition; bioactivity; and application readiness. This review critically examines green recovery strategies and chemical profiling platforms for bioactive compounds recovered from peels; pomace; seed residues; hulls; vegetation waters; and pruning waste. Emphasis is placed on how extraction variables shape chemical profiles; extract quality; and reported biological activities. Ultrasound- and microwave-assisted extraction; enzyme- and fermentation-assisted recovery; supercritical fluid extraction; pressurized liquid extraction; pulsed electric field-assisted pretreatment; and green solvent-based extraction are discussed in terms of target-compound selectivity; solvent and energy demand; process safety; scalability; and sustainability-related evidence. Chromatographic; mass-spectrometric; spectroscopic; and metabolomics-based profiling approaches are evaluated for identification; annotation; quantification; fingerprinting; quality-marker selection; and standardization; with confidence levels distinguished according to authentic-standard matching; tandem mass spectrometry evidence; spectral libraries; or fingerprint-level evidence. Circular valorization pathways in food; nutraceutical; cosmetic; pharmaceutical, and biopesticide-related applications are further considered with attention to feedstock heterogeneity; process standardization; stability; safety; regulatory feasibility; scalability; and techno-economic feasibility. Overall; this review provides a linkage-oriented framework for developing standardized; application-readiness-oriented bioactive candidates from agri-food byproducts. Full article

Multifunctional dressings capable of maintaining a moist environment, supporting tissue regeneration, and delivering bioactive compounds are increasingly being explored as promising strategies for burn wound management. In this study, alginate-based emulgel patches incorporating hydrophilic and lipophilic plant extracts were developed by extrusion-based 3D printing as potential topical systems for burn wound applications. The formulation included sodium alginate, hyaluronic acid, and hydroglyceric extracts of Calendula officinalis, Matricaria chamomilla, and Plantago major, as well as oily extracts of Hippophae rhamnoides and Hypericum perforatum. The emulgel was evaluated for pH, rheological behaviour, spreadability, physical stability, apparent hydrodynamic size distribution, zeta potential, total polyphenol content, and antioxidant activity. Following Ca²⁺-induced crosslinking, uniform and flexible 3D-printed patches were obtained and further characterised for pharmacotechnical, physicochemical, structural, functional, and biological properties. The emulgel exhibited suitable characteristics for extrusion-based printing, while the resulting patches showed good dimensional uniformity, flexibility, swelling capacity, water vapour transmission, and surface pH compatible with topical application. FTIR, DLS, SEM, and SEM–EDX analyses supported the formation of a Ca²⁺-crosslinked alginate network and confirmed the presence of structurally heterogeneous domains with homogeneous calcium distribution. The patches retained plant-derived bioactive compounds, with a total polyphenol content of 0.2878 ± 0.016 mg GAE/g hydrated patch, and showed improved antioxidant activity compared with the corresponding emulgel. In vitro release studies indicated the time-dependent diffusion of polyphenols over 24 h, with cumulative release reaching 64.42%. The patches also exhibited a water vapour transmission rate of 1270 ± 93 g/m²/24 h, indicating adequate moisture regulation. HaCaT cell viability remained above 90% at lower tested concentrations, demonstrating a favourable biocompatibility profile. Overall, the developed 3D-printed alginate emulgel patches represent promising multifunctional systems for potential burn wound management and warrant further preclinical investigation. Full article

Long-horizon mobile manipulation requires a robot to execute a sequence of heterogeneous subtasks such as navigation, picking, and articulated-object manipulation in indoor environments. Standard reinforcement learning suffers from reward sparsity and inefficient exploration in this setting, and hierarchical methods often fail at the hand-off between consecutive subtasks when the terminal state of one subtask is kinematically infeasible for the next. We propose a motion planning-augmented hierarchical reinforcement learning architecture to resolve the fundamental trade-offs between sample efficiency and hand-off reliability in long-horizon mobile manipulation. The mission is decomposed into subtasks via a Semi-Markov Decision Process; within each subtask, a collision-free reference trajectory generated by RRT* in the full joint configuration space is embedded into the reward as a per-step shaping signal; and a region-goal mechanism, defined analytically from inverse kinematics feasibility, replaces rigid coordinate hand-offs with a continuous feasible region. The architecture is evaluated in the ManiSkill-HAB simulation under teleport-free sequential execution and challenging initialization. The proposed method improves subtask success rate and sample efficiency over the baseline across all six evaluated subtasks, and the advantage compounds along the long-horizon task chain. Full article

Periprosthetic joint infection (PJI) remains one of the most severe and complex complications following joint arthroplasty. With the global increase in primary hip and knee replacements, the clinical and economic burden associated with PJI continues to grow. Although relatively uncommon, PJI is linked to substantial morbidity, elevated mortality, and significantly higher healthcare costs compared to aseptic revision procedures. The challenge is compounded by the intricate pathogenesis of biofilm-forming microorganisms, heterogeneous clinical presentations, and the lack of universally standardised diagnostic criteria. This review provides an integrated overview of current evidence concerning the pathophysiology, risk factors, and microbiological patterns associated with PJI. Contemporary diagnostic pathways based on the Musculoskeletal Infection Society/International Consensus Meeting (MSIS/ICM) criteria are summarised, including the utility and limitations of established serological markers, emerging synovial biomarkers such as alpha-defensin, and the complementary roles of culture techniques, histopathology, and molecular assays. Medical and surgical treatment strategies are outlined, including debridement with implant retention, one-stage and two-stage revision approaches, and organism-directed antimicrobial therapy. Preventive strategies spanning preoperative optimisation, intraoperative protocols, and postoperative risk reduction are also highlighted. Despite significant advances, important gaps persist, particularly in antimicrobial resistance, the management of polymicrobial or culture-negative infections, and the treatment of high-risk or immunocompromised patients. Continued interdisciplinary collaboration and high-quality clinical research are essential to refine diagnostic algorithms, improve therapeutic outcomes, and reduce the incidence of this increasingly consequential complication. Full article

Background/Objectives: San-Huang-Xie-Xin-Tang (SHXXT) is a classical traditional Chinese herbal formula composed of Coptis chinensis, Scutellaria baicalensis, and Rheum palmatum, with documented anti-inflammatory and anticancer properties. Despite growing interest in its pharmacological potential, systematic evaluation of its gene regulatory effects across multiple cancer types remains limited. This study aimed to assess the prognostic relevance of SHXXT-regulated genes across pan-cancer contexts using publicly available transcriptomic and clinical datasets. Methods: Fifteen active compounds of SHXXT were identified from traditional Chinese medicine databases (Encyclopaedia of Traditional Chinese Medicine (ETCM) 2.0, Chinese Compound Medicine Database (ccTCM), and Integrated Traditional Chinese Medicine Database (ITCM)). Compound-induced gene expression profiles were obtained from MCF7-based transcriptomic perturbation data in the ITCM database and integrated with The Cancer Genome Atlas (TCGA) across 24 cancer types. Survival-associated genes were evaluated using Cox proportional hazards regression and Kaplan–Meier analysis. A weighted prognostic scoring framework, supported by normalization and sensitivity analyses, was developed to prioritize cancer types according to the concordance between SHXXT-induced gene regulation and favorable prognostic patterns. Functional enrichment analysis was performed using Annotation, Visualization, and Integrated Discovery (DAVID), and cancer-related genes were annotated using the OncoKB database. Complementary in vitro studies, including Annexin V/propidium iodide (PI) and MT-1 staining assays, were conducted in Hep3B cells using a Good Manufacturing Practice (GMP)-certified commercial SHXXT preparation. Results: SHXXT-regulated genes were significantly enriched in cancer-related pathways, particularly the PI3K–Akt and MAPK signaling pathways. Pan-cancer analysis revealed substantial heterogeneity in prognostic alignment across cancer types. Among the 24 cancer cohorts analyzed, kidney renal clear cell carcinoma (KIRC) achieved the highest prognostic alignment score within the proposed framework. In KIRC, several genes, including PIK3CA, PIK3CB, KRAS, and RAF1, remained significantly associated with favorable prognostic alignment after multivariable adjustment. Pathway enrichment analysis further identified PI3K–Akt and MAPK signaling as the most significantly represented pathways among favorably aligned genes. In contrast, hepatocellular carcinoma exhibited a relatively low prognostic alignment score, consistent with in vitro observations indicating predominantly non-selective cytotoxic stress rather than cancer-specific therapeutic activity. Conclusions: SHXXT-regulated genes exhibited marked heterogeneity across cancer types, with KIRC was consistently prioritized as the top-ranked cancer type across multiple analytical scenarios, suggesting a strong concordance between SHXXT-associated gene regulation and favorable prognostic signatures. These findings represent computational predictions derived from transcriptomic and survival associations rather than direct evidence of therapeutic efficacy. The study provides a reproducible pan-cancer strategy for prioritizing candidate cancer types for future mechanistic and experimental validation of traditional Chinese medicine formulations. Full article

Quinoline derivatives constitute a privileged class of nitrogen-containing heterocycles with extensive applications in medicinal chemistry, agrochemicals, materials science, and functional organic materials. Owing to their broad biological and industrial relevance, the development of efficient, selective, and sustainable synthetic methodologies for quinoline construction remains an active area of research. This review provides a comprehensive overview of recent advances in quinoline synthesis, with particular emphasis on catalytic strategies aligned with the principles of green and sustainable chemistry. Classical transformations, including the Friedländer, Skraup, and Povarov reactions, are revisited in the context of modern catalytic developments that improve reaction efficiency, substrate scope, selectivity, and environmental compatibility. Special attention is devoted to homogeneous and heterogeneous catalytic systems based on both platinum-group and earth-abundant transition metals, highlighting the growing importance of borrowing-hydrogen and acceptorless dehydrogenative coupling methodologies. Recent progress in nanocatalysis, photocatalysis, multicomponent reactions, ionic-liquid-mediated transformations, and metal-free protocols is also critically discussed. Furthermore, solvent-free processes, microwave-assisted synthesis, and recyclable catalytic systems are examined as practical approaches toward minimizing waste generation and energy consumption. Mechanistic aspects, catalytic design principles, substrate limitations, and sustainability metrics are evaluated throughout the review to provide a critical perspective on current methodologies. Collectively, the advances summarized herein demonstrate the rapid evolution of quinoline synthesis toward more atom-economical, environmentally benign, and operationally efficient processes, while also identifying future opportunities for the development of next-generation catalytic platforms for quinoline-based heterocycle construction. Full article