Search Results (878)

Efficient production of artemisinin, a valuable secondary metabolite from Artemisia annua, remains a challenge for pharmaceutical applications. This study investigated the use of ex vitro composite plants—generated by inoculation with Agrobacterium rhizogenes strains 2659 and 1523—under hydroponic and aeroponic conditions to enhance artemisinin and phenolic compound accumulation. In leaves, artemisinin content increased in a cultivation-specific, strain-dependent manner: strain 2659 was effective under aeroponics (+36%), while strain 1523 enhanced accumulation under hydroponics (+32%). In roots, strain 2659 led to higher artemisinin accumulation than strain 1523 under both systems, with increases of up to 145% in hydroponics and 75% in aeroponics. Strain 1523 strongly promoted artemisinin exudation, especially in hydroponics, suggesting active regulation of artemisinin export. Aeroponic cultivation increased total phenolic content (TPC) in roots, while strain 1523 reduced TPC in leaves. Although total biomass was unaffected, A. rhizogenes altered assimilate partitioning, decreasing the shoot-to-root ratio and enhancing root metabolism. These findings demonstrate that ex vitro composite plants, combined with optimized soilless cultivation, represent a flexible tool to boost accumulation and secretion of high-value compounds in A. annua. The strain and environment-specific responses emphasize the importance of selecting appropriate bacterial strain–cultivation combinations for scalable production systems. Full article

Background/Objectives: HNSCC is a highly aggressive malignancy marked by the dysregulation of the cell cycle. In HPV⁻ HNSCC, mutations in the CDKN2A gene frequently result in the loss of the p16 protein, a key inhibitor of the cyclin D1/CDK4/6 complex. This loss results in unchecked G1/S phase progression. The CDK4/6 inhibitor palbociclib has shown therapeutic potential in HPV⁻ HNSCC by inducing G1 phase arrest and reducing cell viability. In this study, we investigated the molecular mechanisms by which palbociclib affects cell viability in HPV⁻ HNSCC. Methods: Four HPV⁻ HNSCC cell lines were treated with palbociclib, and RNA sequencing was performed to assess changes in gene expression. Cell viability was measured using the MTT assay. To further investigate protein localization, interactions, and function, we used immunofluorescence staining, co-immunoprecipitation, small molecule inhibitors, and siRNA-mediated knockdown. Results: We demonstrate that palbociclib downregulates survivin, a protein that plays dual roles in mitosis and apoptosis, thereby inhibiting cell proliferation. We also found that survivin is overexpressed in HPV⁻ HNSCC. Inhibiting survivin dimerization using the compound LQZ-7i significantly reduces cell viability and promotes its export from the nucleus to the cytoplasm. Additionally, we identified USP1, a deubiquitinase, as both a downstream target of CDK4/6 and a key regulator of survivin stability. Inhibiting USP1 activity or silencing its expression significantly reduces survivin levels. Conclusions: Our findings highlight survivin as a critical mediator of cell proliferation in HPV⁻ HNSCC and suggest that targeting the CDK4/6-USP1-survivin axis may offer a promising therapeutic strategy. Full article

This study aimed to evaluate the effects of controlled atmosphere (CA) treatment on the postharvest quality of strawberries harvested at different 50% and 80% maturity under export shipping conditions. The strawberries were subjected to CA and refrigerated container (Reefer) environments at 10 °C, and their quality attributes were then analyzed. Metabolomic profiling revealed significant variations in primary and secondary metabolites and volatile organic compounds (VOCs). A pathway analysis revealed that CA conditions altered metabolic pathways related to sugar, amino acid, and energy metabolism during storage. CA treatment effectively delayed the accumulation of anthocyanins and enhanced the levels of specific amino acids and VOCs essential for the flavor and aroma of strawberries. Bioluminescence imaging revealed that CA treatment effectively reduced lipid peroxidation. A correlation analysis showed that certain VOCs and secondary metabolites significantly correlated with lipid peroxidation, indicating their role in enhancing antioxidant activity and reducing oxidative stress. These results suggest that CA conditions are associated with significantly reduced weight loss, the maintenance of firmness, and lower respiration rates in strawberries, particularly in those harvested at 80% maturity, extending the shelf life and improving the sensory quality of strawberries. Therefore, CA treatment is an effective method for long-term export. Full article

Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways—including PI3K–AKT–mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades—undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome–lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3–CR3 axis), and excitatory–inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network “meaning-making”—a collapse of coordinated signal interpretation, triage prioritization, and adaptive response—the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning—a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration. Full article

Background/Objectives: Endozepines known as the endogenous ligands of benzodiazepine-binding sites, include the diazepam binding inhibitor (DBI) and its processing products, the triakontatetraneuropeptide (TTN) and the octadecaneuropeptide (ODN). Despite indisputable evidence of the binding of ODN on GABA_AR-BZ-binding sites, their action on this receptor lacks compelling electrophysiological observations, with some studies reporting that ODN acts as a negative allosteric modulator (NAM) of GABA_AR while others suggest the opposite (positive allosteric modulation, PAM effect). All these studies were carried out in vitro with various neuronal cell types. To further elucidate the role of ODN in neuronal excitability, we tested its effect in vivo in the cerebral cortex of the anesthetized mouse. Methods: Spontaneous neuronal spikes were recorded by means of an extracellular pipette, in the vicinity of which ODN was micro-infused, either at a high dose (10⁻⁵ M) or low dose (10⁻¹¹ M). Results: ODN at a high dose induced a significant increase in neuronal spiking. This effect could be antagonized by the GABA_AR-BZ-binding site blocker flumazenil. In sharp contrast, at low concentrations, ODN reduced neuronal spiking with a magnitude similar to GABA itself. Interestingly, this decrease in neuronal activity by low dose of ODN was not flumazenil-dependent, suggesting that this effect is mediated by another receptor. Finally, we show that astrocytes in culture, known to be stimulated by picomolar doses of ODN via a GPCR, increased their export of GABA when stimulated by low dose of ODN. Conclusion: Our results confirm the versatility of ODN in the control of GABA transmission, but suggest that its PAM-like effect is, at least in part, mediated via an astrocytic non-GABA_AR ODN receptor release of GABA. Full article

This article examines the historical evolution, contemporary dynamics, and future trajectory of China’s legal and judicial framework for pangolin protection. By reviewing over seventy years of regulatory changes, case law, and policy implementation, it outlines three distinct phases: the early emphasis on pangolins as medicinal and export resources (1949–1989); the phase of conflicted protection and utilization under regulatory expansion (1989–2020); and the post-2020 shift toward judicial activism and ecological civil litigation. We then highlight the long-standing contradiction between legislative protection and continued medicinal use, particularly the centuries-old use of pangolins and their derivatives in traditional Chinese medicine, a practice still acknowledged within certain state policies and regulatory frameworks, showing how these inconsistencies enabled persistent illegal exploitation despite regulatory controls. Through systematic analysis of public court records and case databases, the policy historical records reveal a marked increase in environmental public interest litigation since 2020. These lawsuits, often attached to criminal prosecutions, signal a transition from merely punitive approaches to restorative ones—anchored in ecological valuation of species and their services. Case studies illustrate how courts now impose not only wildlife resource loss fees, but also punitive damages and compensation for ecological service function loss. The article will elaborate in detail on the distinctions and interrelations among these types of compensation. The landmark Case No.17 also demonstrates this paradigm shift, wherein courts recognized pangolins’ role in balancing forest ecosystems. However, significant challenges persist. Valuation methodologies lack uniform standards; while the ecological value of pangolins has been recognized, their inherent value as individuals has not been emphasized within the legal system; judicial discretion varies across jurisdictions; and public interest organizations remain underutilized in litigation. Moreover, while the crackdown on organized crime succeeded in curbing mass trafficking, smaller-scale violations tied to cultural consumption for medicine use persist. The article concludes that judicial innovations, such as ecological judicial restoration bases and integration into China’s draft Ecological Environment Code, offer promising pathways forward. To enhance efficacy, it calls for standardization in ecological valuation, strengthened civil society participation, and nuanced differentiation in penal strategies between minor and serious offenses. This study ultimately positions judicial reform as the cornerstone of China’s evolving pangolin conservation strategy. Full article

The effect of creative industries in modern post-industrial realities is increasingly significant, becoming one of the economic drivers for developing countries. The creative sphere is more frequently being considered both in scientific circles and government programs in various countries, and the states of the Eurasian Economic Union (EAEU) are no exception. These countries have significant potential to develop creative industries due to the need for more efficient growth in new areas of the economy. The creative sector, in turn, can stimulate these economies by increasing jobs, heightening export volumes, and attracting investment. Governments are taking active measures to develop this sector by updating the regulatory framework and introducing effective ways to support entrepreneurship. This study analyzes the regulatory legal acts of the EAEU countries in the field of the creative economy. As a result, the main directions of development, measures of state support, and gaps in the existing legislative bases of the countries under consideration were identified. Based on the analysis, the authors have compiled recommendations for the development of policy in the creative sector. The application of the developed recommendations in practice can have a positive impact on the effectiveness of the creative economy’s development, both at the country level and at the level of the Eurasian Economic Union as a whole. Full article

Intracellular alkalosis and extracellular acidosis are two pathological features associated with malignant cells. They offer advantages in terms of invasiveness and proliferation. Extracellular acidification is the consequence of intracellular metabolic changes associated with a higher metabolic rate of cancer cells, potentially inducing dangerous intracellular acidification. To overcome this menace, malignant cells adapt themselves to export hydrogen ions. Therefore, it is reasonable that targeting intracellular alkalinization and extracellular acidification to prompt the reversal of such a pH gradient towards a condition comparable to normal, untransformed cells may represent a strategy helping to contrast malignant behavior. In the present study, we investigated in vitro, in prostate cancer cell models, the biological activity towards intracellular, extracellular and organelle pH of systems of molecules of vegetal origin. A few of these systems were shown to promote intracellular acidification in vitro, whereas others were shown to prevent extracellular acidification and promote lysosomal alkalinization in a cell type-dependent manner. This result clearly indicates that these systems may function as agents interfering with malignant cells inverted pH gradient. Further analysis would be necessary to unravel the cell type specificity of their effects, as well as their mechanism of action. Nevertheless, our proof-of-principle study provides evidence that such systems of molecules can be considered interesting agents in co-adjuvating anti-cancer therapies. Full article

For a long time, the explanation of the various determinants of oil price fluctuations and their impact on economic activity has been based on the supply and demand mechanism. However, with various volatile changes in the international situation in recent years, such as threats to public health and an increase in regional conflicts, special attention has been paid to the geopolitical context as an additional driver of oil price fluctuations. This study examines the relationship between oil price changes and GDP growth and other macroeconomic variables from the perspective of the vulnerability of oil-importing and oil-exporting countries to unexpected oil price shocks, driven by tense geopolitical events, in three European countries (Norway, Germany, and Poland). We apply the Structural Vector Autoregressive (SVAR) model and orthogonalized impulse response functions, based on quarterly data, in regard to two samples: the first spans 1995Q1–2019Q4 (pre-2020 sample), with relatively gradual changes in oil prices, and the second spans 1995Q1–2024Q2 (whole sample), with sudden fluctuations in oil prices due to geopolitical developments. A key finding of this research is that vulnerability to unpredictable oil price shocks related to geopolitical tensions is higher than in regard to expected gradual changes in oil prices, both in oil-importing and oil-exporting countries. Different causality patterns and stronger responses in regard to GDP growth during the period, including in regard to tense geopolitical events in comparison to the pre-2020 sample, lead to the belief that economies are not more resilient to oil price shocks as has been suggested by some studies, which referred to periods that were not driven by geopolitical events. Our research also suggests that countries implementing policies to reduce oil dependency and promote investment in alternative energy sources are better equipped to mitigate the adverse effects of oil price shocks. Full article

This article investigates the macroeconomic and labor market conditions that shape the adoption of artificial intelligence (AI) technologies among large firms in Europe. Based on panel data econometrics and supervised machine learning techniques, we estimate how public health spending, access to credit, export activity, gross capital formation, inflation, openness to trade, and labor market structure influence the share of firms that adopt at least one AI technology. The research covers all 28 EU members between 2018 and 2023. We employ a set of robustness checks using a combination of fixed-effects, random-effects, and dynamic panel data specifications supported by Clustering and supervised learning techniques. We find that AI adoption is linked to higher GDP per capita, healthcare spending, inflation, and openness to trade but lower levels of credit, exports, and capital formation. Labor markets with higher proportions of salaried work, service occupations, and self-employment are linked to AI diffusion, while unemployment and vulnerable work are detractors. Cluster analysis identifies groups of EU members with similar adoption patterns that are usually underpinned by stronger economic and institutional fundamentals. The results collectively suggest that AI diffusion is shaped not only by technological preparedness and capabilities to invest but by inclusive macroeconomic conditions and equitable labor institutions. Targeted policy measures can accelerate the equitable adoption of AI technologies within the European industrial economy. Full article

Stress granule formation is a type of liquid–liquid phase separation in the cytoplasm, leading to RNA–protein condensates that are associated with various cellular stress responses and implicated in numerous pathologies, including cancer, neurodegeneration, inflammation, and cellular senescence. One of the key components of mammalian stress granules is the DEAD-box RNA helicase DDX3, which unwinds RNA in an ATP-dependent manner. DDX3 is involved in multiple steps of RNA metabolism, facilitating gene transcription, splicing, and nuclear export and regulating cytoplasmic translation. In this study, we investigate the role of the RNA helicase DDX3’s enzymatic activity in shaping the RNA content of ribonucleoprotein (RNP) condensates formed during arsenite-induced stress by inhibiting DDX3 activity with RK-33, a small molecule previously shown to be effective in cancer clinical studies. Using the human osteosarcoma U2OS cell line, we purified the RNP granule fraction and performed RNA sequencing to assess changes in the RNA pool. Our results reveal that RK-33 treatment alters the composition of non-coding RNAs within the RNP granule fraction. We observed a DDX3-dependent increase in circular RNA (circRNA) content and alterations in the granule-associated intronic RNAs, suggesting a novel role for DDX3 in regulating the cytoplasmic redistribution of non-coding RNAs. Full article

Cross-border energy trading activity via interconnection has received much attention in Southern Asia to help the South Asian Association for Regional Cooperation (SAARC) region’s energy deficit states. This research article proposed a smart metering system to reduce energy losses and increase distribution sector efficiency. The implementation of smart metering systems in utility management plays a pivotal role in advancing several Sustainable Development Goals (SDGs), i.e.; SDG (Affordable and Clean Energy), and SDG Climate Action. By enabling real-time monitoring, accurate measurement, and data-driven management of energy resources, smart meters promote efficient consumption, reduce losses, and encourage sustainable behaviors among consumers. The adoption of a smart metering system along with Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis, socio-economic analysis, current challenges, and future prospects was also investigated. Besides the economics of the electrical distribution system, one feeder with non-technical losses of about 16% was selected, and the cost–benefit analysis and cost–benefit ratio was estimated for the SAARC region. The import/export ratio is disturbing in various SAARC grids, and a solution in terms of community microgrids is presented from Pakistan’s perspective as a case study. The proposed work gives a guidelines for SAARC countries to reduce their losses and improve their system functionality. It gives a composite solution across multi-faceted evaluation for the betterment of a large region. Full article

Background/Objectives: P-glycoprotein (P-gp), an ATP-binding cassette (ABC) transporter, plays a key role in multidrug resistance by actively exporting chemotherapeutic agents and xenobiotics from cells. Overexpression of P-gp significantly reduces intracellular drug accumulation and compromises treatment efficacy. Despite extensive research, clinically approved P-gp inhibitors remain elusive due to toxicity, poor specificity, and limited efficacy. This study investigates DMH1, a selective type I BMP receptor inhibitor, as a novel P-gp inhibitor. Methods: DMH1 cytotoxicity was assessed in P-gp-overexpressing (PC3-TxR, K562/Dox) and P-gp-deficient (PC3) cell lines using MTT assays. P-gp inhibition was evaluated using calcein AM retention and daunorubicin (DNR) accumulation assays. Kinetic analysis determined DMH1’s effect on P-gp-mediated transport (Vmax and Km). ATPase activity assays were performed to assess DMH1’s impact on ATP hydrolysis. Preliminary molecular docking (CB-Dock2) was used to predict DMH1’s binding site on the human P-gp structure (PDB ID: 6QEX). Results: DMH1 showed no cytotoxicity in P-gp-overexpressing or deficient cells. It significantly enhanced intracellular accumulation of Calcein AM and DNR, indicating effective inhibition of P-gp function. Kinetic data revealed that DMH1 reduced Vmax without affecting Km, consistent with noncompetitive, allosteric inhibition. DMH1 also inhibited ATPase activity in a dose-dependent manner. Docking analysis suggested DMH1 may bind to an allosteric site in the transmembrane domain, potentially stabilizing the inward-facing conformation. Conclusions: DMH1 is a promising noncompetitive, allosteric P-gp inhibitor that enhances intracellular drug retention without cytotoxicity, supporting its potential as a lead compound to overcome multidrug resistance and improve chemotherapeutic efficacy. Full article

Wild-growing edible mushrooms are known to bioaccumulate radionuclides from their environment, particularly the natural isotope potassium-40 (⁴⁰K) and anthropogenic cesium-137 (¹³⁷Cs). However, region-specific data for commercially relevant species in north-eastern Poland remain limited, despite the cultural and economic importance of mushroom foraging and export. This study aimed to assess the radiological safety of wild mushrooms intended for human consumption, with particular attention to regulatory compliance and potential exposure levels. In this study, 230 mushroom samples representing 19 wild edible species were analyzed using gamma spectrometry, alongside composite soil samples collected from corresponding foraging sites. The activity concentration of ¹³⁷Cs in mushrooms ranged from 0.94 to 159.0 Bq/kg fresh mass (f.m.), and that of ⁴⁰K from 64.4 to 150.2 Bq/kg f.m. None of the samples exceeded the regulatory limit of 1250 Bq/kg f.m. for ¹³⁷Cs. The highest estimated annual effective dose was 2.32 µSv from ¹³⁷Cs and 0.93 µSv from ⁴⁰K, with no exceedance of regulatory limits observed in any sample. A strong positive correlation was observed between ¹³⁷Cs activity in soil and mushroom dry mass (Spearman’s Rho = 0.81, p = 0.042), supporting predictable transfer patterns. Additionally, the implications of mushroom drying were assessed considering Council Regulation (Euratom) 2016/52, which mandates radionuclide levels in dried products be evaluated based on their reconstituted form. After such adjustment, even the most contaminated dried samples were found to comply with food safety limits. These findings confirm the radiological safety of wild mushrooms from north-eastern Poland and contribute novel data for a region with limited prior monitoring, in the context of current food safety regulations. Full article

Indonesia’s dependence on fossil fuel exports, particularly coal and crude oil, presents a dual challenge: sustaining economic growth while addressing rising CO₂ emissions. Despite significant attention to domestic energy consumption, the environmental implications of export activities remain underexplored. This study examines the dynamic relationship between energy exports, crude oil prices, and CO₂ emissions in Indonesia using a Vector Autoregressive (VAR) model with annual data from 2002 to 2022. The analysis incorporates Impulse Response Functions (IRFs) and Forecast Error Variance Decomposition (FEVD) to trace short- and long-term interactions among variables. Findings reveal that coal exports are strongly persistent and positively linked to past emission levels, while oil exports respond negatively to both coal and emission shocks—suggesting internal trade-offs. CO₂ emissions are primarily self-driven yet increasingly influenced by oil export fluctuations over time. Crude oil prices, in contrast, have limited impact on domestic emissions. This study contributes a novel export-based perspective to Indonesia’s emission profile and demonstrates the value of dynamic modeling in policy analysis. Results underscore the importance of integrated strategies that balance trade objectives with climate commitments, offering evidence-based insights for refining Indonesia’s nationally determined contributions (NDCs) and sustainable energy policies. Full article