To examine first-year medical students' perceptions of integrating brief, Problem-Based Learning (PBL)-informed medical cases into General and Organic Chemistry laboratories within a traditional 6-year curriculum, and to evaluate Natural Language Processing (NLP)-based sentiment analysis for analysing free-text feedback. First-year medical students participated across two consecutive semesters. Concise, patient-oriented cases were embedded within General Chemistry (fall) and Organic Chemistry (spring) laboratory sessions. After each semester, students completed an anonymous questionnaire with Likert-type items and three open-ended questions addressing challenges, suggested improvements, and overall experience. Quantitative responses were summarised descriptively, with group comparisons by prior experience conducted using chi-square tests. Free-text responses were analysed using NLP-based sentiment analysis in Python. A stratified sample of comments underwent independent sentiment coding by five blinded human raters, and agreement was assessed using Krippendorff's alpha. Response rates were 49% in the fall (106/218) and 52% in the spring (112/215). Overall satisfaction was high across both semesters. Most students agreed that integrated medical cases enhanced understanding of medical concepts, increased engagement and interactivity, and was perceived to support early clinical reasoning. Attitudes did not differ significantly by prior experience with integrated labs. Of 380 open-ended responses, 62.6% were classified by NLP as positive and 12.1% as negative; negative comments focused mainly on time constraints, language barriers, and diagnostic difficulty. Inter-rater agreement among human coders was high (Krippendorff's alpha 0.77), and NLP classifications agreed with the human majority decision in 87% of sampled subset of comments. PBL-informed case integration into first-year chemistry laboratories was associated with high student satisfaction and perceived enhancement of engagement, conceptual understanding, and early clinical reasoning, supporting the value of clinically contextualised laboratory teaching for evidence-based curriculum development in early medical education. In addition, this study demonstrates the potential of combining NLP-based sentiment analysis with targeted human verification as an innovative and scalable methodology for evaluating qualitative student feedback, contributing to the advancement of research and practice in medical education and educational technology. Medical students often find it difficult to see how basic science subjects relate to clinical practice, particularly in the early years of training. In this study, we examined whether adding short, clinically focused medical cases to first-year chemistry laboratory sessions could improve students’ learning experience in a traditional medical curriculum. First-year medical students participated in chemistry laboratories where brief patient cases were used to highlight the medical relevance of the experiments. After completing the sessions, students provided feedback through questionnaires that included both rating scales and open-ended written comments. We analysed these responses using standard statistical methods and computer-based text analysis. Most students reported high satisfaction with the integrated laboratory sessions and felt that the medical cases made the labs more engaging, interactive, and relevant to future clinical practice. Many students also reported that the approach encouraged early clinical reasoning. We found that computer-based analysis of students’ written feedback could reliably summarise overall positive and negative sentiments, although human review was still important for comments suggesting improvements. These findings suggest that simple changes to laboratory teaching can help connect basic science with clinical practice early in medical education and that automated text analysis can support educators in efficiently evaluating student feedback in large courses.
Lithium metal batteries (LMBs), operating at high voltage (>4.2 V), exhibit unprecedented energy density (>400 Wh kg-1), but are restricted by uncontrollable Li dendrites, enigmatic interfacial chemistries, and unstable solid electrolyte interfaces (SEIs). Fluorine, with its high stability, non-flammability, and low cost, is playing an increasingly vital role in high-voltage LMBs and is expected to resolve the above obstacles. Unfortunately, there are few reviews that comprehensively summarise the exquisite design of fluorine engineering in high-voltage LMBs, especially in-depth analysis of its action mechanism in LMBs. In this review, we start with the fundamentals of SEI formation and Li nucleation and deposition, systematically dissecting the exquisite engineering of fluorine chemistry in high-voltage LMBs, including fluorinated electrolyte systems (salts, solvents, additives, etc.), fluorinated polymer-based SEIs, fluorinated collectors and separators. Meanwhile, several targeted and sophisticated cases are handpicked to be portrayed in conjunction with the proposed ideas, aiming to clarify the functionality of fluorine engineering in inhibiting dendrite growth, stabilising SEIs, and minimising safety hazards. Additionally, we highlight the obstacles faced by fluorine chemistry in LMBs and point out its future perspectives. This review provides guidance for the engineering of fluorine chemistry in high-voltage LMBs.
Asparagus officinalis L. (A. officinalis) is a highly representative plant in the Asparagus L. genus, with both edible and medicinal values. As a typical macromolecular metabolite in A. officinalis, A. officinalis L. polysaccharides (AOPs) have attracted much attention due to its rich functional biopolymer properties. AOPs have been proven to have cytotoxic and pro-apoptotic effects, immune regulation, and regulation of intestinal flora, anti-neuritis, anti-atherosclerosis, anti-non-alcoholic liver disease, and other health benefits. Among them, regulation of intestinal flora is the most important health benefit of AOPs. In addition, researchers have developed corresponding drug formulations based on their anti-inflammatory, cytotoxic, and pro-apoptotic effects in practical applications. Through a review of previous studies, researchers have found that plant residues extracted from A. officinalis can be developed into high-value cellulose nanocrystals. This also provides a valuable reference for the reuse of other natural plant waste. In this study, we summarize and review research on AOPs' phytochemical structures, biomedical, and industrial applications, based on the latest research findings and practical considerations.
Microdroplets provide physicochemical environments that differ fundamentally from bulk liquids due to their large surface-to-volume ratios, partial solvation, and pronounced nonequilibrium dynamics. Over the past decade, a growing body of experimental and theoretical work has demonstrated that chemical reactions in microdroplets often exhibit markedly altered kinetics and mechanisms relative to bulk-phase systems. In particular, numerous studies have reported the activation and cleavage of relatively strong covalent bonds under mild conditions in aqueous microdroplets. Recent advances in this field have revealed that microdroplets can act as unique interfacial environments that facilitate bond-breaking reactions. The physicochemical characteristics of microdroplets can reshape reaction energy landscapes and influence reaction pathways. Representative examples of bond activation in microdroplets include C-F, C-H, C-S, C-X, S-O, and O-O bonds. These processes have been proposed to contribute to radical, ionic, or coupled radical-ionic reaction pathways and to alter the behavior of reactive intermediates under confined nonequilibrium conditions. At the same time, the mechanistic origins of many reported microdroplet effects remain actively debated, particularly regarding the roles of interfacial electric fields, spontaneous radical formation, dissolved oxygen, and potential instrumental artifacts. Despite these uncertainties, similar interfacial processes may also operate in natural aqueous microenvironments, particularly in atmospheric aerosols, cloud droplets, and sea spray particles. Interfacial bond cleavage and radical generation may influence sulfur cycling, organic aerosol aging, and the oxidative capacity of the marine boundary layer. Remaining challenges include the spectroscopic detection of transient intermediates, improved scaling between laboratory microdroplet systems and atmospheric particles, and the incorporation of interfacial chemistry into multiphase atmospheric models. Overall, these perspectives highlight the potential of aqueous interfaces as active sites of chemical reactivity linking molecular-scale processes to atmospheric chemistry.
Advanced Glycation End Products (AGEs) accumulate under chronic hyperglycemia and contribute to type 2 diabetes mellitus (T2DM) complications. Three chemical routes generate AGEs in vivo: the Hodge pathway (Amadori rearrangement), the Namiki pathway (Schiff base retroaldol cleavage), and the Wolff pathway (glucose auto-oxidation via Fenton-type chemistry). Each has been extensively characterized, but their integrated behavior in the clinical context - and their relationships to accessible biomarkers - has received less synthetic treatment. This paper provides a clinically oriented mechanistic synthesis of the three pathways, identifying their points of convergence and divergence, and proposes - as a hypothesis-generating organizing schema rather than as established biology - a clinical biomarker mapping linking each pathway to routinely accessible laboratory parameters as a basis for prospective validation. Narrative mechanistic review synthesizing primary biochemistry, dicarbonyl chemistry, and clinical biomarker literatures. The three pathways converge upon a shared reactive dicarbonyl pool comprising methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG); upon the GLO1/GLO2 glyoxalase axis (highest catalytic efficiency for MGO; complementary handling of 3-DG by aldose/aldo-keto reductases); and upon RAGE-mediated inflammatory amplification. They diverge in their dominant kinetic drivers (sustained hyperglycemia for Hodge; glycemic variability for Namiki; oxidative-metal milieu for Wolff) and characteristic AGE adducts. Methylglyoxal also arises substantially from glycolytic triose phosphate degradation independent of the AGE synthesis pathways. We propose that routine laboratory parameters - HbA1c × diabetes duration, glycemic variability indices, hs-CRP, ferritin, gamma-glutamyl transferase, and red cell distribution width - may serve as accessible clinical proxies for pathway-specific activity, with the caveat that these mappings require prospective validation. The Hodge, Namiki, and Wolff pathways are best understood as an integrated AGE synthesis network. This has implications for therapeutic strategy, favoring approaches that act on shared downstream mediators rather than single-pathway interventions, and for the design of pathway-resolved clinical biomarker panels. The proposed mappings and temporal staging are presented as testable hypotheses, not as established clinical algorithms; their validation will require prospective biomarker studies in defined T2DM cohorts.
The net charge on droplets is predicted to play a crucial role in accelerating chemical reactions in microdroplets by either altering reaction energetics or changing surface compositions. However, there are few experimental studies that have explored how the net charge of microdroplets alters their physicochemical properties. Here, we present a new technique to investigate how net charges on levitated microdroplets affect their surface tensions and the partitioning of surfactants to the air-water interface. The technique is validated by measuring how the resonant surface oscillation frequency (ω obs) of microdroplets changes with increasing net charge. For simple one- and two-component microdroplets, ω obs predictably decreases with charge. This enables the determination of surface tension of microdroplets (6-20 µm radius) with net charges approaching the Rayleigh limit (Q R), which represents the maximum net charge a droplet can stably carry before coulombic fission. To demonstrate how this new technique can be used to measure charge-driven changes in surface composition, we measured the dependence of surface tension on charge for microdroplets containing cetrimonium bromide (CTAB). For ∼8 µm-radius microdroplets containing 0.5 mM CTAB, the surface tension was observed to increase from ∼50 to ∼65 mN m-1 as net positive charge on droplets increased from low charge to Q R. A similarly-sized change in surface tension was not observed in negatively charged droplets nor droplets with CTAB concentrations larger than the critical micelle concentration. These initial results demonstrate that the net charge on droplets can alter the equilibrium partitioning of charged surfactants to the air-water interface. Ultimately, the new approach to measure the surface tensions of highly-charged microdroplets enables investigations into how charge alters interfacial concentrations of molecules to promote microdroplet chemistry.
Topological materials have been reported as active and selective electrochemical catalysts for a variety of small-molecule energy-conversion reactions. The exceptional activity and selectivity of these materials have been attributed to their topologically non-trivial surface states, which support chiral spin currents and boast high carrier mobilities. For the topological semimetal PtGa, we find that these states are not robust under practical electrochemical conditions. During electrochemical operation, Ga rapidly corrodes from the surface, yielding a nanoporous, Pt-rich layer. Inductively coupled plasma mass spectrometry and scanning transmission electron microscopy imaging independently confirm Ga corrosion. Hydrogen evolution reaction activity measurements demonstrate that the electrocatalytic performance of PtGa is correlated with the number of Pt active sites, and first-principle calculations further show that introducing Ga vacancies into the PtGa crystal structure disrupts the topologically non-trivial surface states. These observations suggest that previous reports detailing the high electrochemical activity of PtGa might be better explained by an enrichment in Pt active sites following corrosion, rather than by a genuine increase in the intrinsic reaction rate mediated by PtGa's topological surface states. These results urge caution in attributing enhanced catalytic activity to topological surface states without verifying surface composition and electronic structure. They also highlight the distinct meaning of robustness in physics and chemistry.
High-throughput virtual screening of catalysts in organic chemistry remains a grand challenge due to the prohibitive computational cost in exploring vast chemical spaces with quantum-chemical methods. Here, we develop the self-learning diffusion model coupled with potential energy surface exploration (SL-DM-PES) framework, which enables automated high-throughput virtual screening via templated organic reaction pathway construction. This self-learning (SL) framework integrates a general diffusion model (DM) for generating three-dimensional structures of reaction intermediates and transition states directly from two-dimensional molecular graphs, with generalized global neural network potential (GG-NN) calculations for rapid energy evaluation and structure optimization, namely the PES exploration. A high-order pair-reduced equivariant message passing neural network (HPNN-ET) is developed for DM, achieving high precision (RMSE ≤ 0.062 Å) and generality (up to 83 elements) for generating large complexes (up to 362 atoms). As a case study, we applied the SL-DM-PES framework to the Suzuki-Miyaura cross-coupling reaction, using one of the widely accepted mechanisms as the pathway template. Complete reaction profiles of 6883 diverse Pd-phosphine catalysts were generated within 286 GPU hours, costing only $80 overall (about $0.01 per catalyst). With the derived kinetic energy barriers, promising ligands can be predicted, and the prediction is supported by further experiments. SL-DM-PES not only demonstrates the high efficiency of HPNN-ET for complex organic reaction profile generation, but also provides a fast route for reaction screening from first-principles.
MXenes, a rapidly expanding family of two-dimensional transition-metal carbides and nitrides, have emerged as a key material of self-powered wearable electronics and therapeutics owing to their metallic conductivity, mechanical flexibility, and highly tunable surface chemistry. Their integration into piezoelectric nanogenerators and triboelectric nanogenerators (PENGs and TENGs) has substantially advanced mechanical-to-electrical energy conversion in flexible, skin-conformal devices. This review critically examines recent progress in MXene-enabled nanogenerators, covering material synthesis, device architectures, charge-generation mechanisms, and system-level integration. Emphasis is placed on emerging MXene-based composites, including hydrogels, aerogels, nanofibers, and smart textiles, that synergistically integrate energy harvesting, sensing, and mechanical robustness for continuous physiological monitoring, human-machine interfaces, sports analytics, wearable therapeutics and in vivo applications. Key challenges limiting practical deployment, such as oxidation instability, mechanical fatigue, biocompatibility, and scalable manufacturing, are systematically analyzed alongside state-of-the-art mitigation strategies. Finally, future perspectives are outlined, highlighting the convergence of MXene nanogenerators with artificial intelligence, the Internet of Things, and sustainable materials systems to enable autonomous, intelligent, and next-generation, personalized monitoring and therapeutic technologies.
The practical deployment of silicon (Si) anodes is limited by coupled mechanical failure and sluggish electrochemical kinetics arising from repeated volume expansion. While polymer binders are critical to electrode integrity, conventional designs often prioritize mechanical strength over ion transport. Here, a supratopological ion-coordinated binder (PVA-AA-5SAS) by integrating a hyperbranched PVA-AA framework with the sulfonated aromatic small molecule 5-sulfoisophthalic acid sodium salt (SAS) via in situ esterification is developed. The resulting 3D network effectively suppresses polymer chain slippage while simultaneously forming continuous Li+-coordination pathways via cooperative interactions between ester and sulfonate groups. This dual-function architecture markedly accelerates Li+ diffusion, reduces charge-transfer and SEI resistances, and stabilizes interfacial chemistry during deep lithiation. Si electrodes employing this binder demonstrate excellent rate capability and long-term cycling stability, maintaining a capacity retention of 79.2% after 386 cycles at 1 A in a 1 Ah‑level NCM811//SiC550 pouch cell. These results demonstrate that rational binder design can decouple and resolve the long-standing conflict between structural durability and ion conduction, providing a viable route toward kinetically efficient and mechanically durable Si-based batteries.
Water electrolysis is widely acknowledged as a vital pathway for achieving deep decarbonization and facilitating large-scale integration of renewable energy sources. Nonetheless, the anodic oxygen evolution reaction (OER) presents a significant efficiency bottleneck due to its inherently sluggish kinetics associated with multi-electron and proton transfer. In addition to the necessity for high catalytic activity, the long-term stability of OER electrocatalysis has garnered increasing attention. This review focuses on stability under realistic conditions and on understanding and elucidating OER deactivation mechanisms at the microscopic, mesoscopic, and macroscopic levels. At the micro level, the analysis delves into the disruption of dynamic phase equilibrium, stoichiometric deviations caused by selective dissolution, and deactivation resulting from the lattice oxygen mechanism. On the meso scale, it examines the extent of surface reconstruction, the inadequacy of nanomechanical robustness, and catalyst-layer delamination prompted by ripening and agglomeration. At the macro level, it considers corrosion resulting from start-stop cycling, component degradation, and the effects of harsh operational environments. Furthermore, the review summarizes current strategies aimed at enhancing stability, emphasizing intrinsic stability design as a foundational element, supplemented by dynamic stability regulation and optimization of operational conditions. Collectively, these approaches facilitate sustained catalytic performance under high potentials and extended operational periods, paving the way for durable electrocatalytic systems. Lastly, future research should prioritize the stabilization of OER electrocatalysis and its scalable application in industrial water electrolysis.
Sex differences in fear memory are well documented, yet the role of menstrual cycle phases and ovarian hormone dynamics remains unclear. Here, we investigated the individual and combined effects of progesterone and estradiol on fear acquisition and within-session fear extinction in both humans and mice. Human participants included men, women using oral contraceptives, and naturally cycling women across three menstrual phases. Our animal experiment included males and naturally cycling females tested across all estrous stages. Results in humans show an association between high estradiol levels and enhanced within-session extinction, whereas progesterone shows no direct effect. To further explore the relationship between sex hormones and within-session fear extinction, a machine-learning approach (Histogram-based Gradient Boosting Regression Tree) was followed. This showed that the facilitating effect of estradiol on within-session fear extinction is potentiated by its interactions with progesterone. Specifically, a high progesterone to estradiol ratio measured before extinction predicted enhanced extinction in both humans and mice. These findings identify the progesterone to estradiol ratio as a potential translational biomarker of fear extinction, with relevance to sex-informed treatments for fear-related disorders, and uncover a key memory process shared across species.
The increased production of industrial chemicals has led to greater human exposure to endocrine disruptors, such as diethylhexyl phthalate (DEHP). This plasticizer, widely used in hygiene products, packaging, and medical devices, does not covalently bind to polymeric materials, which facilitates its migration and subsequent entry into the human body, primarily via the oral route. In this study, we investigated the effects of DEHP exposure during the lactation period within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. The experimental model utilized Wistar female rats (n=9) that were placed for mating. Litters were standardized to six male pups (n=6) each. DEHP was administered in dams via oral gavage during the lactation (post-natal day, PND 1-21) period to three groups (n=3 dams/group): vehicle, 100 mg/kg/day, and 500 mg/kg/day. After weaning, the offspring were maintained until adulthood.At PND 90, a total of nine male pups (n=3/litters/group) were randomly selected for euthanasia and analyses. At weaning (post-natal day, PND21), animals in the 500DEHP group exhibited reduced body weight and central adiposity, accompanied by increased serum insulin levels, an elevated β-cell function index (HOMA-β), and higher serum total triiodothyronine (T3) levels. By adulthood (PND90), the 500DEHP group developed a delayed obesogenic phenotype, characterized by hyperphagia and increased relative visceral white adipose tissue (vWAT) mass. This phenotype was associated with impaired leptin secretion by vWAT, resulting in reduced circulating leptin levels. Consequently, dysregulation of hypothalamic appetite control pathways was observed, marked by decreased expression of the anorexigenic neuropeptide proopiomelanocortin (POMC) and increased expression of the orexigenic neuropeptide neuropeptide Y (NPY), concomitant with reduced suppressor of cytokine signaling 3 (SOCS3) levels. Notably, elevated serum total T3 levels persisted into adulthood. In contrast, in the 100DEHP group, hypothalamic dysfunction appeared to be the primary target, evidenced by a simultaneous increase in both POMC and NPY expression. Collectively, these findings demonstrate that neonatal exposure to DEHP during lactation influences adult phenotype in a dose- dependent manner. Higher-dose exposure (500 mg/kg/day) compromises peripheral metabolic homeostasis, particularly through vWAT dysfunction and impaired leptin secretion, whereas lower-dose exposure (100 mg/kg/day) preferentially affects central regulation, suggesting dysregulation of hypothalamic neuropeptides.
Bacteriophages are gaining interest due to their potential use against multidrug-resistant bacteria. Here, we investigated the structural dynamics of T7 bacteriophage tail fibers. The T7 virion comprises an icosahedral protein shell and a tail-fiber complex, which is involved in bacterial target recognition and viral DNA injection. The virus has six L-shaped, ∼40-nm-long fibers connected to the tail-tube, which are thought to be essential for initial host recognition and, possibly, for surface exploration. By using high-speed atomic force microscopy (HS-AFM) and molecular dynamics (MD) simulations combined with small angle X-ray scattering (SAXS), we analyzed the molecular structure and movements of isolated tail fibers and tail-fiber complexes. We found that the kink region separating the proximal and distal sections of the fiber acts as a molecular hinge, which allows large-scale dynamic bending. Furthermore, partial unwinding-rewinding in the triple-helical coiled-coil structure of the proximal section permits gross fiber rotation and twisting. The two dynamic regions allow for large-scale, rapid fiber flexing and extension, thus enabling an efficient topological search for anchorage sites by the phage on the host surface. Since the fiber-assisted topological search is likely a universal mechanism of host recognition, modulating it could be used for fine-tuning the phage-bacterium infection process.
Herein, we demonstrate how the chemical sensitivity and mechanical stability of 2D thin films of eutectic gallium indium (eGaIn) can be leveraged to sense the presence of dilute amounts of fluorinated compounds (e.g., per- and polyfluorinated alkyl substances or PFAS). The method utilizes the interfacial interactions between 2D thin films of eGaIn and PFAS microdroplets, which induce thin film delaminations due to the perturbations in the Ga-to-O ratio at the interface. We tested three fluorinated samples - 200 ppm perfluorooctanoic acid (PFOA), 0.014 ppb PFAS, and 0.001 ppb PFAS to investigate the delamination, which exhibits sensitivities to concentrations. We leveraged energy-dispersive X-ray spectroscopy (EDS) and Raman spectroscopy to quantify and probe the shift in elemental distributions and surface dynamics of the eGaIn films. The observed delamination phenomena and the spectroscopic analyses suggest that our method provides a rapid in situ PFAS analysis tool related to total organic fluorine detection, complementing the existing technologies. Such a simplistic tool offers a fast approach to developing low-cost, field-deployable chemical sensors for total organofluorine detection.
Three-dimensional (3D) printing is increasingly used to build electrochemical sensing platforms because it allows researchers to create complex geometries, combine multiple functional components in a single device, and adjust sensor designs to suit specific analytical applications. In this context, fused filament fabrication (FFF) has gained increasing attention for its ability to use conductive thermoplastic filaments and its suitability for rapid design iterations. This review summarizes recent research on electrochemical sensors produced by FFF printing, emphasizing how factors such as printing parameters, filament composition, post-printing processes, and device design affect electrochemical performance. The discussion also addresses ongoing issues with reproducibility, surface accessibility, and inconsistencies in reported performance. In addition, the review considers a range of routinely employed approaches to enhance electrode performance, including mechanical, chemical, and electrochemical activation, and stresses the importance of achieving an appropriate trade-off between sensitivity, stability, and other practical constraints.
Type 2 diabetes has become one of the most common causes of human deaths. Key factors that contribute to the progression of this disease include a sedentary lifestyle, high-fat diet, and genetic abnormalities. Enzyme PTP1B is an important target for researchers as it plays a vital role in performing normal metabolic functions of the human body. Metabolic diseases such as obesity, type 2 diabetes, and cardiovascular complications are due to PTP1B imbalance. It is evident that the overproduction of PTP1B is a prominent factor contributing to the onset and progression of type 2 diabetes. Multiple attempts have been made in recent years to synthesize PTP1B inhibitors but, in most cases, complications were associated with the selectivity and toxicity of the synthesized analogs, which resulted in the failure of their clinical trials. This study comprises a series of ondansetron derivatives, which were developed by employing a one-pot (reductive amination) reaction between ondansetron and substituted anilines to synthesize primary amines as final products. These final products (ondansetron derivatives) were analyzed as PTP1B inhibitors to study the role of enzyme PTP1B in lowering blood glucose levels in conditions such as type 2 diabetes. These novel compounds can provide valuable insights into the development of improved treatment options for diabetes. The synthesized PTP1B inhibitors were subject to in silico, in vitro, and in vivo analysis that revealed encouraging results. The computational data of the selected ligand FN-06 showed highest binding affinity, with the protein PTP1B (1T48) having a docking score of -7.317 kcal/mol. The indicators of the simulation also reflected the stability of the said ligand. Similarly, the results of an in vitro inhibition assay further confirmed that the synthesized compound FN-10 showed direct inhibition of the enzyme PTP1B. Furthermore, animal studies demonstrate the hepatoprotective and anti-diabetic action of the selected compounds FN-06 and FN-10 along with the parent compound ondansetron. The findings of this study suggest that compounds FN-06 and FN-10 may act as lead structures to design potent derivatives, which have antidiabetic activity with hepatoprotective effects.
Ursolic acid (UA), the antimalarial triterpenic mixture 8TTE (containing C-27 feruloyl and coumaroyl esters of ursane and oleane skeletons), and the semi-synthetic antitrypanosomal derivative ursolic acid O-phenyl propionate (UAOPP) exhibit high lipophilicity, which may limit their oral bioavailability. This study aimed to develop lipid nanocapsules (LNCs) to improve the solubility, intestinal permeability, and antiparasitic activity of these triterpenic compounds for potential oral delivery. LNCs formulations containing UA, 8TTE, and UAOPP were prepared and evaluated. A sensitive UPLC\x{2013}MS method was developed and validated for selected triterpenes quantification during transport studies across Caco-2 cell monolayers [limit of detection (LOD): 2 nM; limit of quantification (LOQ): 25 nM]. Cytotoxicity and permeability studies were conducted on Caco-2 cells to assess formulation safety and intestinal transport. In vitro antiparasitic activity of free and formulated compounds was evaluated against Plasmodium falciparum and Trypanosoma brucei brucei (Tbb). The formulations were non-toxic to Caco-2 cells at concentrations up to 2 mg/mL. Permeability studies demonstrated enhanced transport for the formulated triterpenic esters, with permeability increases of up to 2.68-fold, shifting their classification from poorly absorbed to moderately absorbed compounds in humans [apparent permeability coefficient (Papp) > 1 × 10-6 cm/s]. Free UA showed the highest Papp value (4.95 × 10-6 cm/s ± 1.29 × 10-7), but caused epithelial integrity disruption after 2 h of incubation and during the following 48 h, whereas formulated UA induced minimal integrity loss at the same concentration. In antiparasitic assays, blank LNCs exhibited maximum non-toxic concentrations of 165 μg/mL against P. falciparum and 65 μg/mL against Tbb. At these maximum concentrations, formulated UA and 8TTE showed enhanced antiplasmodial activity; however, blank LNCs produced comparable effects. In contrast, UAOPP-loaded LNCs showed significantly improved antitrypanosomal activity by approximately 20% at 2.15 μM (cell viability: 38.20% ± 5.41) compared with free UAOPP (20.38% ± 8.80). These findings suggest that LNCs represent promising oral delivery systems for lipophilic triterpenes. Further in vivo pharmacokinetic and efficacy studies are needed to confirm their therapeutic potential.
Sweet cherry cv. 'Regina' is highly susceptible to rapid postharvest deterioration due to high respiration rate, moisture loss, and ethylene sensitivity, resulting in reduced firmness, stem browning, and decay. This study evaluated the effectiveness of two commercial modified atmosphere packaging films (Fresh Mama and Keep It Fresh) in combination with ethylene scavengers such as potassium permanganate, activated carbon, and their combination in extending the shelf life and preserving fruit quality under ambient (25°C) and refrigerated (4°C) storage. Fruits were assessed for physiological loss in weight (PLW), rot incidence, total soluble solids (TSS), titratable acidity, ascorbic acid, anthocyanin content, and color attributes at defined intervals. Packaging type, ethylene scavenger treatment, and storage conditions significantly (p < 0.05) influenced all quality parameters. Among treatments, Fresh Mama film integrated with potassium permanganate + activated carbon (P3T3) consistently showed superior performance. Under refrigerated storage, PLW was reduced to 3.55% compared to 4.67% in the control; rot incidence remained below 5% up to 70 days, ascorbic acid was retained at 5.91 mg 100 g- 1 compared with 3.03 mg 100 g- 1 in control, and TSS was maintained at 16.83 °Brix. Refrigerated storage (4°C) substantially outperformed ambient storage (25°C) by suppressing respiration, enzymatic activity, and oxidative deterioration. Overall, the integrated use of advanced packaging films with ethylene scavengers, particularly under refrigerated conditions, extended the marketable shelf life of Regina cherries by up to 70 days, offering a practical and commercially viable postharvest management strategy for reducing losses in this highly perishable cultivar.
Correction for 'Thermal-shock-processed thin proton exchange membranes for efficient and durable water electrolysis with reduced hydrogen crossover' by Yuyang Wang et al., Chem. Commun., 2025, 61, 14446-14449, https://doi.org/10.1039/D5CC04399A.