Search Results (1,088)

Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant expression of polysialic acid (PSA), has been linked to increased plasticity, motility, and immune evasion. PSA, a long α2,8-linked sialic acid polymer typically attached to the NCAM, is abundant in the embryonic brain and re-expressed in cancers, correlating with poor prognosis. Here, we investigated how PSA expression was regulated in GBM cells under nutrient-limiting conditions. Serum starvation induced a marked increase in PSA-NCAM, driven by upregulation of the polysialyltransferase ST8SiaIV and an autophagy-dependent recycling of sialic acids from degraded glycoproteins. Inhibition of autophagy or sialidases impaired PSA induction, and PSA regulation appeared dependent on p53 function. Immunohistochemical analysis of GBM tissues revealed co-localization of PSA and LC3, particularly around necrotic regions. In conclusion, we identified a novel mechanism by which GBM cells sustain PSA-NCAM expression via autophagy-mediated sialic acid recycling under nutrient stress. This pathway may enhance cell migration, immune escape, and stem-like properties, offering a potential therapeutic target in GBM. Full article

Every year, a billion tires are discarded worldwide, with only a small percentage being recycled. This leads to significant environmental hazards, such as fire risks and improper disposal. Silty sand also presents technical challenges due to its poor shear strength, susceptibility to erosion, and low permeability. This study explores the incorporation of crumb rubber derived from waste tires into silty sand to enhance its mechanical properties. Crumb rubber particles of varying sizes (3–6 mm, 5–10 mm, and 10–20 mm) were mixed with silty sand at 0%, 3%, 6%, and 9% percentages, respectively. Triaxial compression tests of unconsolidated and consolidated undrained tests with cell pressures of 100, 300, and 500 kPa were conducted. The deviatoric stress, shear stress, and stiffness modulus were investigated. The results revealed that the addition of crumb rubber significantly increased the deviatoric and shear stresses, especially at particle sizes of 5–10 mm, with contents of 3%, 6%, and 9%. Additionally, the stiffness modulus was notably reduced in the mixture containing 6% crumb rubber tire. These findings suggest that incorporating crumb rubber tires into silty sand not only improves silty sand performance but also offers an environmentally sustainable approach to tire waste recycling, making it a viable strategy for silty sand stabilization in construction and geotechnical engineering performance. Full article

Specific venom immunotherapy (VIT) in patients with hymenoptera venom allergy (HVA) represents a well-studied approach to reduce the severity of a possible anaphylactic reaction. Currently, data on mechanisms of tolerance induction at the cellular level within the first hours of therapy are lacking. To address this, total and unoccupied high-affinity IgE receptor (FcεRI) numbers per basophil, soluble FcεRI (sFcεRI) and serum tryptase levels were measured before and after the first day of VIT induction in HVA patients. Additionally, basophil activation tests (BATs) were performed at those time points. In the early phase of VIT induction, no significant change in total FcεRI receptor density on basophils was observed, but a significant increase in unoccupied FcεRI was noticeable, predominantly in patients with high total IgE and low baseline unoccupied FcεRI density. No meaningful difference in serum tryptase levels or sFcεRI levels was observed after VIT induction. BATs showed heterogeneous results, often unchanged before and after VIT (in 47% of the cases), sometimes increased (in 40%) and only rarely decreased EC₅₀ sensitivity (in 13%). Changes in the BAT EC₅₀ correlated with FcεRI receptor density changes in basophils. In summary, VIT induction led to an increased ratio of unoccupied-to-total FcεRI without notable tryptase or sFcεRI serum elevation, pointing towards subthreshold cell activation with receptor internalization and recycling. However, the mostly unchanged or even increased basophil sensitivity in EC₅₀ calls for further research to clarify the clinical relevance of these rapid receptor modulations. Full article

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological mechanisms underlying NAFLD remain unclear, and effective therapeutic strategies are still under investigation. Autophagy, a vital intracellular process in eukaryotic cells, enables the degradation and recycling of cytoplasmic components through a membrane trafficking pathway. Recent studies have demonstrated a strong association between impaired or deficient autophagy and the development and progression of NAFLD. Restoring autophagic function may represent a key approach to mitigating hepatocellular injury. Nevertheless, due to the complexity of autophagy regulation and its context-dependent effects on cellular function, therapeutic strategies targeting autophagy in NAFLD remain limited. This review aims to summarise the relationship between autophagy and NAFLD, focusing on autophagy as a central mechanism. We discuss the latest research advances regarding interventions such as diet and exercise, pharmacological therapies (including modern pharmacological therapy and plant-derived compounds), and other approaches (such as hormones, nanoparticles, gut microbiota, and vitamins). Furthermore, we briefly highlight potential autophagy-related molecular targets that may offer novel therapeutic insights for NAFLD management. Full article

Plastic waste accumulation is one of the most pressing environmental challenges of the 21st century, owing to the widespread use of synthetic polymers and the limitations of conventional recycling methods. Among available strategies, chemical upcycling via depolymerization has emerged as a promising circular approach that converts plastic waste back into valuable monomers and chemical feedstocks. This article provides an in-depth narrative review of recent progress in the upcycling of major plastic types such as PET, PU, PS, and engineering plastics through thermal, chemical, catalytic, biological, and mechanochemical depolymerization methods. Each method is critically assessed in terms of efficiency, scalability, energy input, and environmental impact. Special attention is given to innovative catalyst systems, such as microsized MgO/SiO₂ and Co/CaO composites, and emerging enzymatic systems like engineered PETases and whole-cell biocatalysts that enable low-temperature, selective depolymerization. Furthermore, the conversion pathways of depolymerized products into high-purity monomers such as BHET, TPA, vanillin, and bisphenols are discussed with supporting case studies. The review also examines life cycle assessment (LCA) data, techno-economic analyses, and policy frameworks supporting the adoption of depolymerization-based recycling systems. Collectively, this work outlines the technical viability and sustainability benefits of depolymerization as a core pillar of plastic circularity and monomer recovery, offering a path forward for high-value material recirculation and waste minimization. Full article

Pancreatic cancer is frequently accompanied by cancer-associated cachexia, a debilitating metabolic syndrome marked by progressive skeletal muscle wasting and systemic metabolic dysfunction. This study presents a systems biology framework to simultaneously identify therapeutic targets for both pancreatic ductal adenocarcinoma (PDAC) and its associated cachexia (PDAC-CX), using cell-specific genome-scale metabolic models (GSMMs). The human metabolic network Recon3D was extended to include protein synthesis, degradation, and recycling pathways for key inflammatory and structural proteins. These enhancements enabled the reconstruction of cell-specific GSMMs for PDAC and PDAC-CX, and their respective healthy counterparts, based on transcriptomic datasets. Medium-independent metabolic biomarkers were identified through Parsimonious Metabolite Flow Variability Analysis and differential expression analysis across five nutritional conditions. A fuzzy multi-objective optimization framework was employed within the anticancer target discovery platform to evaluate cell viability and metabolic deviation as dual criteria for assessing therapeutic efficacy and potential side effects. While single-enzyme targets were found to be context-specific and medium-dependent, eight combinatorial targets demonstrated robust, medium-independent effects in both PDAC and PDAC-CX cells. These include the knockout of SLC29A2, SGMS1, CRLS1, and the RNF20–RNF40 complex, alongside upregulation of CERK and PIKFYVE. The proposed integrative strategy offers novel therapeutic avenues that address both tumor progression and cancer-associated cachexia, with improved specificity and reduced off-target effects, thereby contributing to translational oncology. Full article

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance against chemotherapy. Therefore, GGT inhibitors have potential as adjuvants in treating GGT-positive tumors; however, most have been abandoned during clinical trials due to toxicity. Recent studies indicate marine-derived ovothiols as more potent non-competitive GGT inhibitors, inducing a mixed cell-death phenotype of apoptosis and autophagy in GGT-overexpressing cell lines, such as the chronic B leukemic cell HG-3, while displaying no toxicity towards non-proliferative cells. In this work, we characterize the activity of two synthetic ovothiol analogs, L-5-sulfanylhistidine and iso-ovothiol A, in GGT-positive cells, such as HG-3 and HL-60 cells derived from acute promyelocytic leukemia. The two compounds inhibit the activity of membrane-bound GGT, without altering cell vitality nor inducing cytotoxic autophagy in HG-3 cells. We provide evidence that a portion of L-5-sulfanylhistidine enters HG-3 cells and acts as a redox regulator, contributing to the increase in intracellular GSH. On the other hand, ovothiol A, which is mostly sequestered by external membrane-bound GGT, induces intracellular ROS increase and the consequent autophagic pathways. These findings provide the basis for developing ovothiol derivatives as adjuvants in treating GGT-positive tumors’ chemoresistance. Full article

Honey processing is closely linked to water pollution due to the lack of a specific wastewater treatment. This study proposes a sustainable and innovative solution based on two sequential bioprocesses using a real effluent from an Argentine honey-exporting facility. In the initial stage, the honey wastewater was enriched with a non-Saccharomyces yeast (Candida ethanolica), isolated from the same effluent. Treatment with this yeast in a bioreactor nearly doubled the total sugar removal efficiency compared to the control (native flora). Subsequent clarification with diatomaceous earth reduced the optical density (91.6%) and COD (30.9%). In the second stage, secondary sewage effluent was added to the clarified effluent and inoculated with Chlorella vulgaris under different culture conditions. The best microalgae performance was observed under high light intensity and high inoculum concentration, achieving a fivefold increase in cell density, a specific growth rate of 0.752 d⁻¹, and a doubling time of 0.921 d. Although total sugar removal in this stage remained below 28%, cumulative COD removal reached 90% after nine days under both lighting conditions. This study presents the first integrated treatment approach for honey industry effluents using a native yeast–microalgae system, incorporating in situ effluent recycling and the potential for dual waste valorization. Full article

Herpes simplex virus type 1 (HSV-1) has a global prevalence of 64%. Established antiviral drugs, such as acyclovir (ACV), have been successfully used over the past decades. However, due to growing viral resistance against approved antivirals and the lack of effective vaccines, new concepts are essential to target HSV-1 infections. Here, we present data on the inhibitory effect of the procaine-based substance ProcCluster^® (PC) in reducing HSV-1 replication in vitro. Non-toxic PC concentrations significantly decreased HSV-1 replication in infected cells. Immunofluorescence microscopy revealed an accumulation of viral proteins in early and recycling endosomes, resulting in reduced viral release. The combination of PC with ACV resulted in an enhanced antiviral effect. Based on these results, PC alone, as well as in combination with ACV, appears to be a promising substance with antiviral potential against HSV-1 infections. Full article

Rail transit as a high-energy consumption field urgently requires the adoption of clean energy innovations to reduce energy consumption and accelerate the transition to new energy applications. As an energy-saving fluid machinery, the ejector exhibits significant application potential and academic value within this field. This paper reviewed the recent advances, technical challenges, research hotspots, and future development directions of ejector applications in rail transit, aiming to address gaps in existing reviews. (1) In waste heat recovery, exhaust heat is utilized for propulsion in vehicle ejector refrigeration air conditioning systems, resulting in energy consumption being reduced by 12~17%. (2) In vehicle pneumatic pressure reduction systems, the throttle valve is replaced with an ejector, leading to an output power increase of more than 13% and providing support for zero-emission new energy vehicle applications. (3) In hydrogen supply systems, hydrogen recirculation efficiency exceeding 68.5% is achieved in fuel cells using multi-nozzle ejector technology. (4) Ejector-based active flow control enables precise ± 20 N dynamic pantograph lift adjustment at 300 km/h. However, current research still faces challenges including the tendency toward subcritical mode in fixed geometry ejectors under variable operating conditions, scarcity of application data for global warming potential refrigerants, insufficient stability of hydrogen recycling under wide power output ranges, and thermodynamic irreversibility causing turbulence loss. To address these issues, future efforts should focus on developing dynamic intelligent control technology based on machine learning, designing adjustable nozzles and other structural innovations, optimizing multi-system efficiency through hybrid architectures, and investigating global warming potential refrigerants. These strategies will facilitate the evolution of ejector technology toward greater intelligence and efficiency, thereby supporting the green transformation and energy conservation objectives of rail transit. Full article

This study analyses the greenhouse gas reduction potential of different end-of-life (EoL) strategies based on a case study of light electric vehicles (LEVs). Using a shared electric moped scooter as a reference, four EoL scenarios are evaluated in a comparative life cycle assessment (LCA). The modelling of the scenarios combines different R-strategies (e.g., recycling, reusing, and repurposing) regarding both the vehicle itself and the battery. German and EU regulations for vehicle and battery disposal are incorporated, as well as EU directives such as the Battery Product Pass. The global warming potential (GWP₁₀₀) of the production and EoL life cycle stages ranges from 644 to 1025 kg CO₂ eq among the four analysed scenarios. Landfill treatment led to the highest GWP₁₀₀, with 1.47 times higher emissions than those of the base scenario (status quo treatment following EU directives), while increasing component reuse and repurposing the battery cells achieved GWP₁₀₀ reductions of 2.8% and 7.8%, respectively. Overall, the importance of implementing sustainable EoL strategies for LEVs is apparent. To achieve this, a product design that facilitates EoL material and component separation is essential as well as the development of political and economic frameworks. This paper promotes enhancing the circularity of LEVs by combining the LCA of EoL strategies with eco-design considerations. Full article

There is an increasing demand for the development of efficient and sustainable battery recycling processes. Currently, many recycling processes rely on toxic inorganic acids to recover materials from high-value battery chemistries such as lithium nickel manganese cobalt oxides (NMCs) and lithium cobalt oxide (LCOs). However, as cell manufacturers seek more cost-effective battery chemistries, the value of the spent battery value chain is increasingly diluted by chemistries such as lithium iron phosphate (LFPs). These cheaper alternatives present a difficulty when recycling, as current recycling processes are geared towards dealing with high-value chemistries; thus, the current processes become less economical. To date, much research is focused on treating a single battery chemistry; however, often, the feed material entering a battery recycling facility is contaminated with other battery chemistries, e.g., LFP feed contaminated with NMC, LCO, or LMOs. This research aims to selectively leach various battery chemistries out of a mixed feed material with the aid of a green organic acid, namely oxalic acid. When operating at the optimal conditions (2% solids, 0.25 M oxalic acid, natural pH around 1.15, 25 °C, 60 min), this research has proven that oxalic acid can be used to selectively dissolve 95.58% and 93.57% of Li and P, respectively, from a mixed LFP-NMC mixed feed, all while only extracting 12.83% of Fe and 8.43% of Mn, with no Co and Ni being detected in solution. Along with the high degree of selectivity, this research has also demonstrated, through varying the pH, that the selectivity of the leaching system can be altered. It was determined that at pH 0.5 the system dissolved both the NMC and LFP chemistries; at a pH of 1.15, the LFP chemistry (Li and P) was selectively targeted. Finally, at a pH of 4, the NMC chemistry (Ni, Co and Mn) was selectively dissolved. Full article

Galectin-3 (Gal-3) is a β-galactoside-binding lectin that mediates diverse signaling events in multiple cell types, including immune cells. It is also a prognostic indicator for multiple clinically important disorders, including cardiovascular disease. Gal-3 binds to cell surface glycans to form lattices that modulate surface receptor signaling and internalization. However, the tissue-specific regulation of Gal-3 surface expression remains poorly understood. Here, we review evidence for the involvement of Gal-3 in cell surface signaling, intranuclear events, and intracellular trafficking. Our focus will be on the O-GlcNAc modification as a regulator of Gal-3 biosynthesis, non-canonical secretion, and recycling. We argue that the nutrient-driven cytoplasmic hexosamine biosynthetic pathway (HBP) and endomembrane transport mechanisms generate unique pools of nucleotide sugars. The differing levels of nucleotide sugars in the cytosol, endoplasmic reticulum (ER), and Golgi apparatus generate differential thresholds for the responsiveness of O-GlcNAc cycling, N- and O-linked glycan synthesis/branching, and glycolipid synthesis. By regulating Gal-3 synthesis and non-canonical secretion, O-GlcNAc cycling may serve as a nexus constraining Gal-3 cell surface expression and lattice formation. This homeostatic feedback mechanism would be critical under conditions where extensive glycan synthesis and branching in the endomembrane system and on the cell surface are maintained by elevated hexosamine synthesis. Thus, O-GlcNAc cycling and Gal-3 synergize to regulate Gal-3 secretion and influence cellular signaling. In humans, Gal-3 serves as an early-stage prognostic indicator for heart disease, kidney disease, viral infection, autoimmune disease, and neurodegenerative disorders. Since O-GlcNAc cycling has also been linked to these pathologic states, exploring the interconnections between O-GlcNAc cycling and Gal-3 expression and synthesis is likely to emerge as an exciting area of research. Full article

Background and Objectives: VPS26A, a core component of the retromer complex, is pivotal to endosomal trafficking and membrane protein recycling. However, its expression profile, prognostic significance, and clinical relevance in liver hepatocellular carcinoma (LIHC) remain unexplored. This study investigates the prognostic potential of VPS26A by extensively analyzing publicly available LIHC-related databases. Materials and Methods: Multiple databases, including TIMER, UALCAN, HPA, GSCA, KM Plotter, OSlihc, MethSurv, miRNet, OncomiR, LinkedOmics, GeneMANIA, and STRING, were used to evaluate VPS26A expression patterns, prognostic implications, correlations with tumor-infiltrating immune cells (TIICs), epigenetic modifications, drug sensitivity, co-expression networks, and protein–protein interactions in LIHC. Results: VPS26A was significantly overexpressed at both the mRNA and protein levels in LIHC tissues compared to that in normal tissues. This upregulation was strongly associated with a poor prognosis. Furthermore, VPS26A expression was both positively and negatively correlated with various TIICs. Epigenetic analysis indicated that VPS26A is regulated by promoter and regional DNA methylation. Additionally, VPS26A influences the sensitivity of LIHC cells to a broad range of anticancer agents. Functional enrichment and co-expression analyses revealed that VPS26A serves as a central regulator of the LIHC transcriptomic landscape, with positively correlated gene sets linked to poor prognosis. Additionally, VPS26A contributes to the molecular architecture governing vesicular trafficking, with potential relevance to diseases involving defects in endosomal transport and autophagy. Notably, miRNAs targeting VPS26A-associated gene networks have emerged as potential prognostic biomarkers for LIHC. VPS26A was found to be integrated into a highly interconnected signaling network comprising proteins in cancer progression, immune regulation, and cellular metabolism. Conclusions: Overall, VPS26A may serve as a potential prognostic biomarker and therapeutic target in LIHC. This study provides novel insights into the molecular mechanisms underlying LIHC progression, and highlights the multifaceted role of VPS26A in tumor biology. Full article

Polyethylene terephthalate (PET) pollution represents a significant environmental challenge due to its widespread use and recalcitrant nature. PET-degrading enzymes, particularly Ideonella sakaiensis PETases (IsPETase), have emerged as promising biocatalysts for mitigating this problem. This review provides a comprehensive overview of recent advancements in the discovery and heterologous expression of IsPETase and closely related enzymes. We highlight innovative approaches, such as in silico and AI-based enzyme screening and advanced screening assays. Strategies to enhance enzyme secretion and solubility, such as using signal peptides, fusion tags, chaperone co-expression, cell surface display systems, and membrane permeability modulation, are critically evaluated. Despite considerable progress, challenges remain in achieving industrial-scale production and application. Future research must focus on integrating cutting-edge molecular biology techniques with host-specific optimisation to achieve sustainable and cost-effective solutions for PET biodegradation and recycling. This review aims to provide a foundation for further exploration and innovation in the field of enzymatic plastic degradation. Full article