Search Results (290)

The widespread presence of polystyrene microplastics (PS-MPs) and agricultural pollutants such as avermectin (AVM) in aquatic environments poses a significant threat to aquatic organisms. However, the combined toxic effect of PS-MPs and AVM on cardiac development remains poorly understood. This study aimed to investigate the cardiac toxicity of AVM co-exposed with two sizes of MPs (large MPs, LMPs, 20 µm; small MPs, SMPs, 80 nm) in both larval and adult zebrafish. Firstly, under the co-exposure conditions of MPs and AVM, we observed significant cardiac developmental toxicity, including decreased survival rate, body length, and hatching rate, as well as a significant reduction in the number of myocardial cells. Secondly, the number of neutrophils and antioxidant enzyme activities such as CAT and SOD were greatly decreased, while inflammatory cytokines such as TNF-α and IL8 were significantly increased after co-exposure in larval zebrafish. Thirdly, there was severe disorganization of cardiomyocytes and interstitial edema in adult zebrafish hearts under the co-exposure by histopathological examination. Our results suggest that cardiomyocyte proliferation was suppressed, but heart apoptosis level and anti-apoptotic genes were significantly increased in the AVM+MPs co-exposure. Additionally, transcriptome sequencing and bioinformatics analysis revealed that significant changes in differentially expressed genes in the AVM+SMPs co-exposure group, particularly in the processes related to oxidation–reduction, inflammatory response, and the MAPK signaling pathway in the adult zebrafish heart. Furthermore, our pharmacological experiments demonstrated that inhibiting ROS and blocking the MAPK signaling pathway could partially rescue the heart injury induced by AVM and MPs co-exposure in both larval and adult zebrafish. In summary, this study suggested that co-exposure to AVM and MPs could induce heart toxicity mainly via the ROS-mediated MAPK signaling pathway in zebrafish. The information provided important insights into the potential environmental risk of microplastic and pesticide co-exposure on aquatic ecosystems. Full article

In the last three decades, significant progress has been made to find, develop, test, and qualify advanced green monopropellants which have the potential to replace hydrazine in satellite propulsion to a large extent due to their lower health risks, environmentally friendliness, and interesting or even better performance properties. Some ADN- and HAN-based monopropellant blends have meanwhile reached high TRL levels. The ADN-based blend LMP-103S, is an energetic ionic liquid (EIL) and is used onboard more than 25 satellites. It was the first green EIL used in space and currently has the most applications. HAN-based monopropellant blends like AF-M315E also have several applications on satellites. Nevertheless, intensive research and development activities are furthermore conducted on the way to a mature green propulsion technology base and to identify and test further species and monopropellant mixtures, which could or seem to promise even better properties and may have also the potential to replace hydrazine. This paper provides an overview on the properties of developed monopropellants and interesting candidates for orbital satellite propulsion in the thrust range up to approximately 200 N. It discusses types of monopropellants, used species, and mixtures broader than in previous review and overview publications listed in the Introduction, and considers the status up to summer 2025. Full article

Hericium erinaceus (Lion’s Mane mushroom) is a medicinal species recognised for its neuroprotective and antioxidant properties. This study investigated its potential as a functional ingredient in oat milk-based desserts formulated for individuals with dysphagia. Freeze-dried Lion’s Mane powder (LMP), containing high-quality protein (~16%, amino acid score 88%), dietary fibre (~31%), and phenolic compounds (72.15 mg GAE/g), was incorporated at varying levels using gelatin or iota-carrageenan (IC) as gelling agents. Incorporation of up to 5% LMP significantly improved the nutritional composition and maintained favourable texture and sensory characteristics while meeting the International Dysphagia Diet Standardisation Initiative (IDDSI) Level 6 criteria. Both manual and instrumental fork pressure tests confirmed that all samples were soft and easy to compress without stickiness or deformation recovery, ensuring safe swallowing. Higher inclusion levels of LMP or hydrocolloids increased hardness and firmness but adversely affected colour and mouthfeel. Carrageenan-based formulations further supported the development of vegan-friendly options with stable structure and desirable rheology. Overall, the study demonstrates that Lion’s Mane-enriched soft foods can deliver enhanced nutrition and texture suitable for dysphagic diets, offering a novel, plant–fungal approach to supporting healthy ageing with potential neuroprotective properties. Full article

The lysosome is no longer viewed as a simple degradative “trash can” of the cell. The lysosome is not only degradative; its acidic, redox-active lumen also serves as a chemical “microreactor” that can modulate anticancer drug disposition and activation. This review examines how the distinctive chemical features of the lysosome, including its acidic pH (~4.5–5), strong redox gradients, limited thiol-reducing capacity, generation of reactive oxygen (ROS), diverse acid hydrolases, and reservoirs of metal ions, converge to influence the fate and activity of anticancer drugs. The acidic lumen promotes sequestration of weak-base drugs, which can reduce efficacy by trapping agents within a protective “safe house,” yet can also be harnessed for pH-responsive drug release. Lysosomal redox chemistry, driven by intralysosomal iron and copper, catalyzes Fenton-type ROS generation that contributes to oxidative damage and ferroptosis. The lysosome’s broad enzyme repertoire enables selective prodrug activation, such as through protease-cleavable linkers in antibody–drug conjugates, while its membrane transporters, particularly P-glycoprotein (Pgp), can sequester chemotherapies and promote multidrug resistance. Emerging therapeutic strategies exploit these processes by designing lysosomotropic drug conjugates, pH- and redox-sensitive delivery systems, and combinations that trigger lysosomal membrane permeabilization (LMP) to release trapped drugs. Acridine–thiosemicarbazone hybrids exemplify this approach by combining lysosomal accumulation with metal-based redox activity to overcome Pgp-mediated resistance. Advances in chemical biology, including fluorescent probes for pH, redox state, metals, and enzymes, are providing new insights into lysosomal function. Reframing the lysosome as a chemical reactor rather than a passive recycling compartment opens new opportunities to manipulate subcellular pharmacokinetics, improve drug targeting, and overcome therapeutic resistance in cancer. Overall, this review translates the chemical principles of the lysosome into design rules for next-generation, more selective anticancer strategies. Full article

Chronic inflammation constitutes a significant characteristic of sustained infections caused by viral and fungal pathogens, with a strong correlation to the development of cancer, autoimmune disorders, and tissue fibrosis. Viral proteins such as HIV-1 Tat, HBV X (HBx), HPV E6/E7, and EBV LMP1 modulate the host’s immune signaling pathways, primarily through the activation of the NF-κB signaling cascade and the disruption of cytokine equilibrium. These molecular interactions result in a pro-inflammatory microenvironment that facilitates viral persistence, immune evasion, and the process of oncogenesis. Structural investigations have elucidated the mechanisms by which these viral proteins interact with host signaling complexes, thereby highlighting their potential as viable therapeutic targets. Similarly, fungal proteins, including secreted aspartyl proteases (Saps), ribotoxin Asp f1, and chitin-binding proteins, incite chronic inflammation by activating pattern recognition receptors and triggering inflammasome activation. Despite the limited structural information of these fungal proteins, emerging models and bioinformatic analyses identified conserved motifs that are crucial for host interactions. Biologic therapies, encompassing antiviral and antifungal peptides as well as monoclonal antibodies, are currently under development to disrupt these protein-host interactions and modulate inflammatory responses. This review provides structural and functional insight into viral and fungal inflammatory proteins and evaluates the potential of biologics as targeted therapeutic interventions for chronic inflammation associated with infections. We discuss the ongoing clinical trials involving neutralizing antibodies targeting HIV, peptide vaccines aimed at HPV and other promising molecules. Finally, we discuss the current limitations of biologics and possible solutions to translate these promising therapeutics into clinical practice. Full article

Liver transplantation represents the only curative method for end-stage liver disorders and certain liver malignancies. Over the last three decades, advancements in immunosuppression, surgical technique, and intensive care measures have resulted in improved patient and graft survival outcomes, but a deficit of donor organs is constantly the major issue that limits our ability to reduce the mortality on the liver transplant waiting list. To address this, marginal grafts and those from donors after cardiac death are increasingly employed, but these strategies necessitated novel methods to improve the preservation and quality of liver grafts and the most promising one is liver machine perfusion (LMP). LMP evolved significantly in the past 10 years, and consequently, it is gradually establishing itself as a standard protocol at many transplant centers. However, many unresolved questions remain concerning the indications, types, and protocols associated with LMP. Therefore, continuous research is necessary to determine optimal guidelines and recommendations for its clinical application. This review aims to analyze the development of liver machine perfusion, including its different modalities underlying mechanisms of operation, and provide an overview of its historical evolution, current status, and future prospects. Full article

Background/Objectives: Identifying novel targets to treat gastric cancer (GC) has become a focus of research in recent years. Our accelerated Helicobacter-induced gastric cancer mouse model allowed us to identify several differentially expressed genes (DEGs), including Psmb8 (proteasome subunit beta type 8, also called Lmp7), which was also found to be elevated in GC patient samples. PSMB8 encodes one of the immune subunits of the immunoproteasome, which has been associated with disease severity in multiple cancers. Methods: We identified carfilzomib from a public database as a potential drug targeting PSMB8; it effectively halts immunoproteasome activity, leading to apoptosis. We tested carfilzomib’s efficacy against gastric cancer by subcutaneously implanting nude mice with human gastric epithelial-derived tumors and treating them with carfilzomib, either alone or in combination with 5-fluorouracil (5-FU), a standard-of-care drug. The effectiveness of drug treatment was measured by tumor growth, cell proliferation, and apoptosis. Results: We observed that carfilzomib retarded tumor growth, inhibited cell proliferation, and induced apoptosis. Conclusions: These results strongly suggest that PSMB8 is a suitable candidate for targeted therapy. Moreover, with carfilzomib having robust anti-tumor activity, it has potential as a treatment option for cancers where high levels of PSMB8 are associated with poor overall survival. Full article

Background/Objectives: Melanoma cells enhance glycolysis and expand lysosomes to support energy metabolism, proliferation, and metastasis. However, lysosomal membrane permeabilization (LMP) causes cathepsin leakage into cytosol triggering cytotoxicity. This study investigated the antimelanoma effect of 2-deoxy-D-glucose (2DG), an inhibitor of glycolytic enzyme hexokinase-2, in combination with cathepsin C-dependent LMP inducer L-leucyl-L-leucine methyl ester (LLOMe) and cathepsin C-independent LMP-inducers mefloquine and siramesine. Methods: The viability of A375 and B16 melanoma cells and primary fibroblasts was measured by crystal violet. Apoptosis, necrosis, and LMP were assessed by flow cytometry; caspase activation, mitochondrial depolarization, superoxide production, and energy metabolism were analyzed by fluorimetry, and expression of cathepsins and hexokinase-2 was evaluated by immunoblot. Appropriate inhibitors, antioxidant, and energy boosters were used to confirm cell death type and mechanism. Results: LLOMe triggered LMP, mitochondrial depolarization, and mitochondrial superoxide production, while suppressing oxidative phosphorylation. 2DG suppressed glycolysis and, together with LLOMe, synergized in ATP depletion, caspase activation, and mixed apoptosis and necrosis in A375 cells. Inhibitors of lysosomal acidification, cysteine cathepsins, and caspases, as well as antioxidant and energy boosters, reduced 2DG+LLOMe-induced toxicity. Cathepsins B, C, and D were lower, while hexokinase-2 was higher in A375 cells than fibroblasts. Accordingly, 2DG exhibited lower while LLOMe exhibited higher toxicity against fibroblasts than A375 and B16 cells. However, mefloquine and siramesine induced stronger LMP in A375 cells than in fibroblasts and showed melanoma-selective toxicity when combined with 2DG. Conclusions: 2DG-mediated glycolysis inhibition in combination with lysosomal destabilization induced by mefloquine and siramesine, but not with non-selectively toxic LLOMe, may be promising antimelanoma strategy. Full article

With the development of electricity spot markets, the integrated renewable-storage plant (IRSP) has emerged as a crucial entity in real-time energy markets due to its flexible regulation capability. However, traditional methods face computational inefficiency in high-dimensional bidding scenarios caused by expansive decision spaces, limiting online generation of multi-segment optimal quotation curves. This paper proposes a policy migration-based optimization framework for high-dimensional IRSP bidding: First, a real-time market clearing model with IRSP participation and an operational constraint-integrated bidding model are established. Second, we rigorously prove the monotonic mapping relationship between the cleared output and the real-time locational marginal price (LMP) under the market clearing condition and establish mathematical foundations for migrating the self-dispatch policy to the quotation curve based on value function concavity theory. Finally, a generalized inverse construction method is proposed to decompose the high-dimensional quotation curve optimization into optimal power response subproblems within price parameter space, substantially reducing decision space dimensionality. The case study validates the framework effectiveness through performance evaluation of policy migration for a wind-dual energy storage plant, demonstrating that the proposed method achieves 90% of the ideal revenue with a 5% prediction error and enables reinforcement learning algorithms to increase their performance from 65.1% to 84.2% of the optimal revenue. The research provides theoretical support for resolving the “dimensionality–efficiency–revenue” dilemma in high-dimensional bidding and expands policy possibilities for IRSP participation in real-time markets. Full article

The emergence of human coronaviruses has led to three epidemics or pandemics in the last two decades, collectively causing millions of deaths and thus highlighting a long-term need to identify new antiviral drug targets and develop antiviral therapeutics. In this study, a compound library was screened to uncover novel potential inhibitors of coronavirus replication. Three lead compounds, designated #16-14, #16-23, and #16-24, which were Ixazomib and its analogs, were identified based on their potent antiviral activity and minimal cytotoxicity. These compounds were found to inhibit the immunoproteasome subunit LMP7, a target whose subcellular localization and expression are altered in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected Huh7 cells. Yeast two-hybrid assays and co-immunoprecipitation further revealed that LMP7 interacts with the viral proteins Nsp13 and Nsp16. In addition, Nsp13 and Nsp16 disrupted the expression of LMP7 in response to pathogen attacks. Functional studies showed that LMP7 knockout in BEAS-2B-ACE2 cells resulted in enhanced replication of attenuated SARS-CoV-2, highlighting the role of this subunit in restricting viral replication. Taken together, these findings position LMP7 as a novel therapeutic target and highlight Ixazomib and its analogs as potential antiviral agents against current and future coronavirus threats. Full article

Background/Objectives: Epstein–Barr virus (EBV) detection patterns in lymphoproliferative disorders (LPDs) show significant geographical variation worldwide. Regional epidemiological data are essential for understanding viral distribution patterns and developing appropriate clinical surveillance strategies. This study aimed to determine EBV detection frequency in LPDs using available molecular and immunohistochemical methods in Western Mexico. Methods: We conducted a cross-sectional study of 200 formalin-fixed paraffin-embedded tissue samples from patients diagnosed with LPDs (2015–2019) at Hospital Civil de Guadalajara. EBV detection combined with real-time PCR targeting the BNTp143 gene and immunohistochemistry for LMP-1 protein. Cases were classified following current WHO criteria. Statistical analysis included multivariate logistic regression, diagnostic concordance assessment, and age-stratified analysis. Results: EBV detection frequency reached 35.5% overall, with marked differences between neoplastic (53.9%) and reactive LPDs (24.2%) (OR: 3.515; 95% CI: 1.859–6.645, p < 0.001). Hodgkin lymphoma showed the highest detection rate (80.6%), significantly exceeding non-Hodgkin lymphoma (39.3%) (OR: 6.43; 95% CI: 2.08–19.41, p = 0.001). Age-stratified analysis revealed predominant adult involvement (49.1% vs. 22.0% in young adults, p = 0.025). We identified three epidemiological categories based on detection probability patterns. Conclusions: This study represents the first comprehensive molecular and immunohistochemical characterization of Epstein–Barr virus in lymphoproliferative disorders from Western Mexico, establishing distinct epidemiological patterns that align with Latin American regional characteristics. The validated methodology provides a reproducible framework for multi-center studies, while the epidemiological data serve as an essential baseline for future longitudinal research and resource optimization in similar healthcare settings. Full article

This study evaluated the effects of dietary probiotic-fermented corn wet distillers grains (FCWDGs) on finishing pigs. Three Bacillus subtilis strains (CGMCC21218, CCTCC2022073, and CICC10275) were used to ferment corn wet distillers grains, yielding FCWDGs-1, FCWDGs-2, and FCWDGs-3. A total of 128 130-day-old Anqing six white pigs were randomly assigned to four groups: a control group and groups supplemented with 6% FCWDGs-1 (T1), FCWDGs-2 (T2), and FCWDGs-3 (T3). Over a 60-day trial, FCWDGs significantly enhanced growth performance, with T1 and T3 groups showing higher final weight and average daily gain (ADG) compared to the control (p < 0.05), and feed-to-gain ratios were reduced in all treatments (p < 0.05). Loin muscle depth (LMD) was significantly greater in all treatments (p < 0.05), and the lean meat percentage (LMP) was significantly higher in the T1 group (p < 0.05). Antioxidant activity (T-AOC, SOD, and GSH-Px) was enhanced in all treatments, with the highest values observed in the T1 group (p < 0.05). Notably, FCWDGs reduced heavy-metal residues (As, Pb, Cu) in muscle, liver, and kidney tissues, particularly in the T1 group. The results highlight the potential of Bacillus subtilis-fermented FCWDGs to enhance growth performance and carcass traits, and reduce heavy metal accumulation in pig tissues. Full article

Optimizing the metabolizable protein level in ruminant diets represents a promising strategy to increase nitrogen use efficiency and mitigate environmental pollution. This study explored the impacts of varying metabolizable protein (MP) levels on amino acid (AA) balance, nitrogen (N) utilization, and the ruminal microbiota in Hu lambs. Fifty-four female Hu lambs of 60 d old, with an average body weight (BW) of 18.7 ± 2.37 kg, were randomly allocated to three dietary MP groups: (1) low MP (LMP, 7.38% of DM), (2) moderate MP (MMP, 8.66% of DM), and (3) high MP (HMP, 9.93% of DM). Three lambs with similar BW within each group were housed together in a single pen, serving as one experimental replicate (n = 6). The feeding trial lasted for 60 days with 10 days for adaptation. The final BW of lambs in the MMP and HMP groups increased (p < 0.05) by 5.64% and 5.26%, respectively, compared to the LMP group. Additionally, lambs fed the MMP diet exhibited an 11.6% higher (p < 0.05) average daily gain than those in the LMP group. Increasing dietary MP levels enhanced (p < 0.05) N intake, urinary N, retained N, and percent N retained, but decreased apparent N digestibility (p < 0.05). Urinary uric acid, total purine derivatives, intestinally absorbable dietary protein, microbial crude protein, intestinally absorbable microbial crude protein, and actual MP supply all increased (p < 0.05) with higher MP values in the diet. The plasma concentrations of arginine, lysine, methionine, phenylalanine, threonine, aspartic acid, proline, total essential AAs, and total nonessential AAs were the lowest (p < 0.05) in the LMP group. In the rumen, elevated MP levels led to a significant increase (p < 0.05) in the ammonia N content. The relative abundances of Candidatus_Saccharimonas, Ruminococcus, and Oscillospira were the lowest (p < 0.05), whereas the relative abundances of Terrisporobacter and the Christensenellaceae_R-7_group were the highest (p < 0.05) in the MMP group. In conclusion, the moderate dietary metabolizable protein level could enhance growth performance, balance the plasma amino acid profiles, and increase nitrogen utilization efficiency in Hu lambs, while also altering the rumen bacterial community by increasing beneficial probiotics like the Christensenellaceae_R-7_group. Full article

Liquid metals (LMs), with their unique combination of high electrical conductivity and mechanical deformability, have emerged as promising materials for stretchable electronics and biointerfaces. However, the practical application of bulk LMs in wearable sensors has been hindered by processing challenges and low stability. To overcome these limitations, liquid metal particles (LMPs) encapsulated by native oxide shells have gained attention as versatile and stable fillers for stretchable and conductive composites. Recent advances have focused on the development of LM-based hybrid composites that combine LMPs with metal, carbon, or polymeric fillers. These systems offer enhanced electrical and mechanical properties and can form conductive networks without the need for additional sintering processes. They also impart composites with multiple functions such as self-healing, electromagnetic interference shielding, and recyclability. Hence, the present review summarizes the fabrication methods and functional properties of LM-based composites, with a particular focus on their applications in wearable sensing. In addition, recent developments in the use of LM composites for physical motion monitoring (e.g., strain and pressure sensing) and electrophysiological signal recording (e.g., EMG and ECG) are presented, and the key challenges and opportunities for next-generation wearable platforms are discussed. Full article

The electricity market can optimize the resource allocation in power systems by calculating the market clearing problem. However, in the market clearing process, various market operation requirements must be considered. These requirements might cause the obtained power system dispatch instructions to deviate from the optimal solutions of original market clearing problems, thereby compromising the economic properties of locational marginal price (LMP). To mitigate the adverse effects of such optimality limitations, this paper proposes a pricing method for improving economic properties under the optimality limitation of power system dispatch instructions. Firstly, the underlying mechanism through which optimality limitations lead to economic property distortions in the electricity market is analyzed. Secondly, an analytical framework is developed to characterize economic properties under optimality limitations. Subsequently, an optimization-based electricity market pricing model is formulated, where price serves as the decision variable and economic properties, such as competitive equilibrium, are incorporated as optimization objectives. Case studies show that the proposed electricity market pricing method effectively mitigates the economic property distortions induced by optimality limitations and can be adapted to satisfy different economic properties based on market preferences. Full article