Search Results (554)

Tyrosinase (EC 1.14.18.1) is the primary enzyme responsible for melanogenesis in mammals and enzymatic browning in food, creating a high demand for potent, safe inhibitors of this enzyme in the cosmetic, medical, and agricultural sectors. Conventional synthetic inhibitors often face limitations concerning their cytotoxicity and stability, necessitating the exploration of marine natural products (MNPs). Marine algae, comprising macroalgae (seaweeds) and microalgae (including cyanobacteria), represent an underexploited source of structurally diverse bioactives. Macroalgae, particularly brown species, yield complex phlorotannins, such as the non-competitive oligomer dieckol, which exhibits an IC50 of 2.16 µg/mL. Conversely, microalgae deliver high-potency, low-molecular-weight compounds, notably the synthesizable scytonemin monomer (ScyM) with an IC50 of 4.90 µM—significantly stronger than kojic acid. Mechanistic analysis, supported by molecular docking, reveals diverse modes of action, from the two-step slow binding of complex phlorotannins to the highly specific competitive binding of red algal bromophenols. Translational success requires the consistent application of green extraction techniques, such as Natural Deep Eutectic Solvents (NADESs), and advanced delivery systems, like Nanostructured Lipid Carriers (NLCs), to ensure the stability and bioavailability of these compounds for future cosmeceutical and medical applications. Full article

Cathepsin B (CatB) is a lysosomal cysteine protease that plays a major role in various pathologies and is therefore considered a valuable therapeutic target. To address species-specific inhibitor challenges, we characterized the selective binding of designed ankyrin repeat protein (DARPin) 4m3 toward mouse cathepsin B (mCatB) over human CatB (hCatB). The mCatB–DARPin 4m3 complex was validated by size-exclusion chromatography (SEC), nano-differential scanning fluorimetry (nano-DSF), and surface plasmon resonance (SPR), revealing high affinity binding (K_D = 65.7 nM) and potent inhibition (Ki = 26.7 nM; mixed competitive/noncompetitive). DARPin 4m3 showed no binding/inhibition toward hCatB. The 1.67 Å crystal structure of the complex—the first for mCatB—identified key interaction residues (e.g., I65/Q66 in mCatB vs. S65/M66 in hCatB) conferring selectivity. Proteomic analysis of endogenous substrates using a support vector machine (SVM) revealed greater similarity between mCatB and hCatB cleavages (Area Under the Curve (AUC) = 0.733) than between mCatB and other human cathepsins (AUC = 0.939–0.965). Clustering and SVM methods offer broadly applicable tools for protease specificity profiling in drug discovery. This study demonstrates the utility of DARPins for species-selective targeting and highlights the importance of integrated structural and proteomic approaches for dissecting protein–protein interactions. Full article

Plant protease inhibitors (PPI) play a significant role against microbes, insects, and, to a considerable extent, human pathogens. PPIs inactivate hydrolase enzymes or depolarize the plasma membrane of the pathogens, thereby inhibiting their growth, replication, and invasion. Here, an active serine protease inhibitor was isolated and purified from the seeds of Cleome viscosa. The purified inhibitor was homogenous and exhibited a molecular weight of around 12 kDa as a monomer. The secondary structure analysis indicated that the inhibitor was predominantly composed of α-helical content. The kinetics experiments demonstrated a noncompetitive mode of inhibition towards serine protease when casein was used as the enzyme substrate. The inhibitor formed a stable complex with serine protease, having a likely 1:1 stoichiometry, as inferred from ITC, and the dissociation constant was examined to be K_d = 1.9 × 10⁻⁶ M with a Gibbs free energy of ΔG = −8.079 (kcal/mol). The inhibitor exhibits stable protease inhibition up to 90 °C. Further, in vitro preliminary studies revealed its inhibitory effects against HSV-2 function, evidence that it may have a role in the treatment of viral infections. Full article

The Berberis nummularia fruit is rich in polyphenols and which are associated with the inhibition of carbohydrate-digesting enzymes. However, the phytochemical compositions, antioxidant strength, and the ability of the fruits on the inhibition of α-amylase to control postprandial blood glucose remained elusive. In this study, therefore, different concentrations of ethanol were used in ultrasound processing at 70 °C for 1 h to obtain the crude polyphenol of B. nummularia fruit (CPB) and obtain the purified polyphenol (PPB) using AB-8 macroporous resin. After this, the polyphenolic constituents within PPB were identified using LC-MS/QTOF and investigated for anti-hyperglycemic properties by sucrose loading test. The results showed that the optimal extraction yield (44.32 ± 2.08%) of CPB was achieved with 30% ethanol and the PPB from CPB was reached at 71.88 ± 2.74%. A total of 30 polyphenols including 13 phenolic acids, 13 flavonoids, 3 benzaldehyde derivatives, and 1 aromatic acid were identified, in which the caffeic acid had the highest content (426.20 ± 0.18 ng/mg). The PPB displayed potent α-amylase inhibitory activity with an IC₅₀ value of 69.91 μg/mL and kinetic analysis via Lineweaver–Burk double reciprocal plots confirmed a non-competitive inhibition mechanism. Moreover, at an administration dose of 100 mg/kg body weight (BW), PPB significantly reduced blood glucose levels by 13.75 ± 0.87% and exerted a marked ameliorative effect on postprandial hyperglycemia in vivo. Therefore, these findings provide a foundation for considering PPB as a beneficial functional food ingredient and a potential dietary supplement for the management of postprandial hyperglycemia. Full article

Background/Objectives: This study mapped parent/guardian–child physical activity (PA) inequities across racial and ethnic groups in the Americas. Method: A systematic scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) and the Joanna Briggs Institute guidelines. Searches were carried out in January 2025 in the following databases: SciELO, LILACS, Web of Science, MEDLINE, EMBASE, Scopus, Web of Science, SPORTDiscus, and PsycINFO. Eligible studies were original articles that jointly assessed parents/guardians and children from diverse racial and ethnic backgrounds. Results: 4195 articles were found, and a total of 25 studies were included (cross-sectional design n = 20). Among these, 18 studies reported that higher parental/guardian PA was associated with greater child PA, regardless of race and ethnic background. Only seven studies provided explicit race and ethnic comparisons (six cross-sectional and one cohort). In four studies Black/African American parents/guardians and children were less physically active than their White counterparts; one study of Latino families showed lower participation in sports compared with African Americans; in one study Hispanic, African American, and Asian families had lower odds of engaging in PA compared with White peers; and one study of African American and Mexican American families reported lower participation in non-competitive individual sports than Anglo families. Conclusions: This review demonstrates consistent associations between parental/guardian and child PA, although a few studies reported null or inverse findings. Moreover, racial and ethnic inequalities in intergenerational PA reflect broader structural health inequities, where access to time, space, and resources for movement remains unevenly distributed. Full article

Cardiovascular magnetic resonance (CMR) imaging is a key component of current diagnostic pathways in subjects with acute myocarditis. The 2020 ESC Guidelines on Sports Cardiology recommend athletes with acute myocarditis to abstain from sports during the recovery phase from inflammation and to undergo comprehensive evaluation—including CMR—before safely returning to play. This retrospective study analyzed 95 non-competitive athletes presenting with acute myocarditis and evaluated by initial and repeated CMRs. CMR exams assessed myocardial inflammation, edema, and scarring as defined based on the updated Lake Louise criteria. As per 2020 ESC Guidelines, eligibility was granted by excluding extensive myocardial damage. Initial CMR showed 84% positive STIR (edema) and 79% with LGE ≥ 3 segments. After 3–6 months, STIR positivity dropped to 12%, LGE extent remained globally stable, but with some reduction in 42%. Few experienced recurrent myocarditis or LVEF decline; 24% met return-to-play criteria by repeated CMR. Our study shows that few non-competitive athletes recovering from acute myocarditis meet ESC CMR criteria to resume competitive sports at prescribed follow-up evaluation. The long-term prognostic value of CMR markers like LGE and edema remains unclear, highlighting the need for further research to refine return-to-play guidelines and ensure athlete safety. Full article

Inhibition of agonist-induced M₂ muscarinic receptor (M₂R) activation by functional anti-M₂R autoantibodies has been associated with cardiac parasympathetic dysfunction in patients with chronic Chagas disease (CD). This study explored the allosteric nature of that inhibitory effect by assessing the ability of serum IgG from patients with CD and dysautonomia (DCD IgG) to modulate the interaction between M₂R and β-arrestins in HEK 293T cells using bioluminescence resonance energy transfer. DCD IgG alone did not stimulate arrestin-2 or arrestin-3 recruitment. When cells were preincubated with DCD IgG and then treated with carbachol, arrestin-2 translocation decreased in a concentration-dependent manner, while arrestin-3 recruitment remained unaffected. Inhibition curve analysis showed a submaximal inhibitory effect (68.1 ± 2.4%) and a Hill slope less than −1 (−4.03 ± 0.39). Carbachol concentration–response assays after preincubation with DCD IgG revealed a noncompetitive inhibition of arrestin-2 recruitment, with no change in arrestin-3 translocation. Unlikely, simultaneous exposure to DCD IgG and carbachol potentiated agonist-induced Arr-2 recruitment. We conclude that anti-M₂R autoantibodies selectively inhibit agonist-induced arrestin-2 recruitment, acting as negative allosteric modulators of agonist efficacy. The direction of autoantibody-induced allosteric modulation depends on the timing of IgG application relative to the agonist and the duration of receptor exposure to autoantibodies. Full article

This study examines the dynamic decoupling relationship between energy consumption and export growth in China since its accession to the World Trade Organization (WTO) (2002–2018) by combining the noncompetitive input–output model, Tapio decoupling model, and the Logarithmic Mean Divisia Index (LMDI) model. The results reveal the substantial energy consumption generated by China’s export trade, emphasizing the urgency of reducing energy consumption in export trade for energy conservation and emissions reduction. Since its WTO accession, China has experienced sustained improvement in the energy decoupling effect during the growth of export trade, entering a period of strong decoupling from 2014 to 2018. The expanded export scale remains a major obstacle to decoupling export trade growth from energy consumption, while decreased energy intensity in exports is a significant driving force for energy decoupling, with relatively minor impact from changes in the export trade structure. By integrating non-competitive input–output modeling, Tapio decoupling analysis, and LMDI decomposition, this study develops a novel framework to investigate the structural drivers of energy–export decoupling in China from 2002 to 2018. Bridging methods from energy systems, trade economics, and policy modeling, it contributes to the field of multi-disciplinary sustainability by offering sector-level insights and decomposition-based evidence to support more efficient, equitable, and sustainable trade transitions. Full article

The phytohormone abscisic acid (ABA) plays a central role in organizing adaptive responses in plants to various abiotic stresses, helping the plant minimize the negative impact on growth and development. Rapid and direct detection of ABA is valuable for investigating plant responses to abiotic stress. In this work, we propose a novel label-free, non-competitive immunoassay for detecting and quantifying ABA easily and rapidly using a surface plasmon resonance (SPR) biosensor. The SPR sensor chip was functionalized with a commercial anti-ABA antibody, characterized for its affinity, binding kinetics, and specificity using the same platform. The direct assay demonstrated high specificity and sensitivity, with a calculated limit of detection of 1.36 ng/mL in buffer. The new immunosensor was applied to determine ABA concentrations directly in xylem sap samples from tomato plants subjected to abiotic stress (drought and high salinity) and was able to accurately reflect ABA levels corresponding to the applied stress. The results were comparable to the reference method, ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), establishing this new immunosensor as a novel detection method for rapid and reliable monitoring of ABA levels associated with abiotic stress in tomato plants. Full article

Although associative interference has traditionally been attributed to retrieval competition, emerging evidence suggests that interference may also arise from encoding-based representational processes. The present study examined whether retroactive interference (RI) and proactive interference (PI) can occur in the absence of explicit retrieval competition and whether they reflect distinct underlying mechanisms. Participants studied two lists of word–picture pairs in an AB/AC associative learning paradigm, followed by a non-competitive two-alternative forced-choice (2AFC) associative recognition test and a source memory task. Across both frequentist and Bayesian analyses, recognition accuracy revealed a significant RI effect—lower accuracy for earlier A-B pairs relative to non-overlapping controls—whereas PI manifested as longer reaction times (RTs) for later A-C pairs, despite comparable accuracy. Source judgments showed faster correct responses for overlapping than for non-overlapping pairs, suggesting that cue overlap facilitated more fluent retrieval rather than confusion. These findings indicate that interference can emerge independently of retrieval competition and that RI and PI are supported by dissociable mechanisms: RI reflects encoding-related reorganization that weakens earlier associations, whereas PI reflects increased retrieval effort following differentiation of overlapping traces. Together, the results support a process-interaction framework in which encoding-based reactivation and reorganization shape later retrieval dynamics, demonstrating that associative interference arises from the interplay between encoding and retrieval processes rather than retrieval competition alone. Full article

Self Determination Theory posits that individuals may be more likely to initiate and maintain behaviors tied to intrinsic (vs. extrinsic) motivations and may provide a useful framework for understanding youth participation in novel sports. Using the Intrinsic Motivation Inventory (IMI) and Patient-Centered Assessment and Counseling for Exercise Plus Nutrition (PACE+) surveys, motivation and physical activity habits were explored in 27 children/adolescents (ages 7–16) enrolled in Parkour, an individual, non-competitive youth sport. Fifteen Parkour participants were also interviewed to gain an understanding of their motivations for participating. Study participants had high median IMI subscale scores related to interest/enjoyment (6.71/7) and perceived choice (6.40/7) compared to the whole scale. Similarly median sub-scale Pros and Self-Efficacy scores for physical activity from the PACE+ were high (4.25/5 and 3.91/5, respectively). The themes of autonomy and enjoyment were consistently reported in the qualitative interviews, expanding on the quantitative results. Other themes included appreciation for camaraderie, creativity, and a drive for improvement. These results provide early evidence that Parkour, and similar lifestyle sports, may be tied more to intrinsic than extrinsic motivations and could have potential for adoption and maintenance by youth with low motivation to engage in physical activity to promote healthy behaviors. Full article

Seaweed holds significant promise as a renewable feedstock for bioenergy due to its rapid growth, carbon sequestration capacity, and non-competition with terrestrial agriculture. This review examines recent progress in multi-method synergies for optimized energy conversion from seaweed biomass. Physical pre-treatments (e.g., drying, milling, ultrasound, microwave) enhance substrate accessibility but face energy intensity constraints. Chemical processes (acid/alkali, solvent extraction, catalysis) improve lipid/sugar recovery and bio-oil yields, especially via hydrodeoxygenation (HDO) and catalytic cracking over tailored catalysts (e.g., ZSM-5), though cost and byproduct management remain challenges. Biological methods (enzymatic hydrolysis, fermentation) enable eco-friendly valorization but suffer from scalability and enzymatic cost limitations. Critically, integrated approaches—such as microwave-solvent systems or hybrid thermochemical-biological cascades—demonstrate superior efficiency over singular techniques. Upgrading pathways for liquid bio-oil (e.g., HDO, catalytic pyrolysis) show considerable potential for drop-in fuel production, while solid-phase biochar and biogas offer carbon sequestration and circular economy benefits. Future priorities include developing low-cost catalysts, optimizing process economics, and scaling synergies like hydrothermal liquefaction coupled with catalytic upgrading to advance sustainable seaweed biorefineries. Full article

Glutamate receptors represent a potential target for neuroprotection in neurodegenerative neurological conditions. Perampanel, a non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist, is clinically approved for the management of epilepsy. Perampanel’s neuroprotective effects have been reported in global and focal cerebral ischemia models, but the cellular mechanisms remain incompletely understood. Therefore, we studied the potential neuroprotective effects of perampanel in rats using the pial vessel disruption (PVD) stroke model, an established focal cortical non-reperfusion ischemic stroke model. Perampanel was given once intraperitoneally (3 mg/kg body weight) 1 h after PVD surgery and repeated on days 2–3 post-surgery. On the fourth day post PVD, animal behavioral assays and imaging, biochemical, and electrophysiological analyses were performed. Compared to vehicle control, perampanel in PVD-treated rats significantly inhibited hippocampal neurodegeneration and long-term potentiation deficits. Perampanel also attenuated PVD-induced motor deficits, depressive/anxiety-like behaviors, and hippocampal-dependent cognitive impairment. In addition, perampanel prevented the PVD-induced downregulation of surface-expressed GluA1 and GluA2 AMPARs and increased phosphorylation of GluA1 at S831 and S845. Molecular docking analysis revealed perampanel binding to transmembrane regions M1, M3 and M4 of GluA1 and GluA2 subunits. Together, our results show that perampanel attenuated PVD-induced neurodegeneration and behavioral deficits by blocking AMPARs and decreasing GluA1 and GluA2 internalization. In addition, this study shows the neuroprotective potential of perampanel through the inhibition of neuroinflammation mediated by activated microglia and astrocytes following cerebral ischemia. This study is the first to evaluate perampanel in the pial vessel disruption model of ischemia without reperfusion, a clinically relevant stroke paradigm that differs fundamentally from middle cerebral carotid artery occlusion and photothrombosis stroke models. Full article

To address the greenhouse effect and environmental pollution stemming from fossil fuels, the development of new energy sources is widely regarded as a critical pathway toward achieving carbon neutrality. Microalgae, as a feedstock for third-generation biofuels, have emerged as a research hotspot for producing biojet fuel due to their high photosynthetic efficiency, non-competition with food crops, and potential for carbon reduction. This paper provides a systematic review of technological advancements in the catalytic hydrogenation of microalgal oil for biojet fuel production. It specifically focuses on the reaction mechanisms and catalyst design involved in the hydrogenation–deoxygenation and cracking/isomerization processes within the Oil-to-Jet (OTJ) pathway. Furthermore, the paper compares the performance differences among various catalyst support materials and between precious and non-precious metal catalysts. Finally, it outlines the current landscape of policy support and progress in industrialization projects globally. Full article

Cannabidiol (CBD) is a chemical produced by the cannabis plant that acts as an allosteric modulator of cannabinoid receptors resulting in non-competitive receptor antagonism in the central nervous system. This mechanism of action leads to anti-convulsant, anti-anxiety, and analgesic properties with minimal psycho-activity, which has led to significant interest in the use of CBD as a medication. Legislation around cannabis has changed in recent years, with many states permitting the use of CBD-based products as “medication” without approval from the Federal Drug Administration. This has led to a proliferation of products with associated marketing claims that are often unsubstantiated. This review summarizes the evidence for cannabidiol as a medical treatment, focusing on epilepsy, mental health, behavioral and substance use disorders occurring in pediatric and adolescent populations for which information is available. CBD preparations have been approved by the FDA to treat epilepsy in childhood; no other indications currently exist, and the literature remains inconclusive. Few adverse effects related to CBD use have been reported. However, endogenous cannabinoids play an important role in guiding brain development, and the long-term impact of modulating the endocannabinoid system during periods of brain growth during childhood and adolescence is unknown. While there is excitement about the potential for the development of CBD medications, currently, there is very limited information about the long-term safety of CBD, especially in children and adolescents, and caution is recommended regarding the use of unregulated, unapproved CBD preparations that are currently available over the counter. Full article