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20 pages, 2452 KiB  
Article
The Importance of Solution Studies for the Structural Characterization of the Enterovirus 5’ Cloverleaf
by Morgan G. Daniels, Meagan E. Werner, Xiaobing Zuo and Steven M. Pascal
Viruses 2025, 17(8), 1127; https://doi.org/10.3390/v17081127 (registering DOI) - 16 Aug 2025
Abstract
Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5’ cloverleaf (5’CL). Here, we present a biophysical analysis of the 5’CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD [...] Read more.
Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5’ cloverleaf (5’CL). Here, we present a biophysical analysis of the 5’CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD spectroscopy, size-exclusion chromatography, and small-angle X-ray scattering. In general, a tendency toward a smaller monomeric hydrodynamic radius in the presence of salts was observed, but the exact structural signature of each 5’CL varied depending upon the serotype. Rhinovirus B14 (RVB14) exhibited at least two monomeric conformations and a low propensity for dimerization, while poliovirus 1 (PV1) showed a high propensity for dimerization, which was enhanced by the presence of salts. Enterovirus D70 was observed to be somewhat intermediate, with primarily a monomeric structure, but possessing some potential for dimerization. The equilibrium between the two monomeric and the dimeric conformations is also discussed. These results indicate that the 5’CL conformation may be more complex than the current literature suggests, thus underscoring the need for a combined crystal and solution approach for the accurate representation of the 5’CL conformation, and the conformation of other RNA structural elements, under native conditions. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research, 2nd Edition)
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21 pages, 5020 KiB  
Article
Divergent Hepatic and Adipose Tissue Effects of Kupffer Cell Depletion in a Male Rat Model of Metabolic-Associated Steatohepatitis
by Morena Wiszniewski, Diego Mori, Silvia I. Sanchez Puch, Camila Martinez Calejman, Cora B. Cymeryng and Esteban M. Repetto
Biology 2025, 14(8), 1058; https://doi.org/10.3390/biology14081058 - 15 Aug 2025
Abstract
Kupffer cells (KCs) play a pivotal role in the progression of metabolic-associated steatohepatitis (MASH). This study evaluated the impact of short-term KC depletion induced by gadolinium chloride (GdCl3) in a rat model of MASH. The intervention with GdCl3 effectively reduced [...] Read more.
Kupffer cells (KCs) play a pivotal role in the progression of metabolic-associated steatohepatitis (MASH). This study evaluated the impact of short-term KC depletion induced by gadolinium chloride (GdCl3) in a rat model of MASH. The intervention with GdCl3 effectively reduced KC markers CD68 and Clec4f, together with pro-inflammatory cytokines (IL-1β, TNFα, NOS2), without affecting anti-inflammatory markers (IL-10, MRC1). Histologically, GdCl3 reduced hepatocyte ballooning and NAS despite persistent steatosis. KC depletion was associated with decreased oxidative stress markers (TBARS, 3-nitrotyrosine) and antioxidant enzyme activity (SOD, catalase). Additionally, markers of endoplasmic reticulum stress (ATF4, GRP78, CHOP, P58IPK) and apoptosis (BAX/BCL2 ratio, cleaved caspase-3) were diminished. Despite these improvements, GdCl3 had no effect on lipid or glucose metabolism in the liver, associated with persistent elevation of PTP1B expression induced by SRD intake. KC depletion, however, increased FGF21 expression. GdCl3 treatment improved systemic insulin sensitivity and reduced fasting glucose and NEFA serum levels. In white adipose tissue, the treatment decreased adipocyte size, restored insulin signaling, and inhibited lipolysis (ATGL expression) without altering macrophage infiltration (IBA) or thermogenic protein levels (UCP1) in SRD rats. These findings suggest that KC depletion modulates liver-to-adipose tissue crosstalk, potentially through FGF21 signaling, contributing to improved systemic metabolic homeostasis of SRD animals. Full article
(This article belongs to the Special Issue Cellular and Molecular Biology of Liver Diseases)
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21 pages, 980 KiB  
Article
Remediation of Heavy Metal-Contaminated Soils Using Phosphate-Enriched Sewage Sludge Biochar
by Protogene Mbasabire, Yves Theoneste Murindangabo, Jakub Brom, Protegene Byukusenge, Jean de Dieu Marcel Ufitikirezi, Josine Uwihanganye, Sandra Nicole Umurungi, Marie Grace Ntezimana, Karim Karimunda and Roger Bwimba
Sustainability 2025, 17(16), 7345; https://doi.org/10.3390/su17167345 - 14 Aug 2025
Viewed by 17
Abstract
Heavy metals represent long-lasting contaminants that pose significant risks to both human health and ecosystem integrity. Originating from both natural and anthropogenic activities, they bioaccumulate in organisms through the food web, leading to widespread and long-lasting contamination. Industrialization, agriculture, and urbanization have exacerbated [...] Read more.
Heavy metals represent long-lasting contaminants that pose significant risks to both human health and ecosystem integrity. Originating from both natural and anthropogenic activities, they bioaccumulate in organisms through the food web, leading to widespread and long-lasting contamination. Industrialization, agriculture, and urbanization have exacerbated soil and water contamination through activities such as mining, industrial production, and wastewater use. In response to this challenge, biochar produced from waste materials such as sewage sludge has emerged as a promising remediation strategy, offering a cost-effective and sustainable means to immobilize heavy metals and reduce their bioavailability in contaminated environments. Here we explore the potential of phosphate-enriched biochar, derived from sewage sludge, to adsorb and stabilize heavy metals in polluted soils. Sewage sludge was pyrolyzed at various temperatures to produce biochar. A soil incubation experiment was conducted by adding phosphate-amended biochar to contaminated soil and maintaining it for one month. Heavy metals were extracted using a CaCl2 extraction method and analyzed using atomic absorption spectrophotometry. Results demonstrated that phosphate amendment significantly enhanced the biochar’s capacity to immobilize heavy metals. Amending soils with 2.5 wt% phosphate-enriched sewage sludge biochar led to reductions in bioavailable Cd (by 65–82%), Zn (40–75%), and Pb (52–88%) across varying pyrolysis temperatures. Specifically, phosphate-amended biochar reduced the mobility of Cd and Zn more effectively than unamended biochar, with a significant decrease in their concentrations in soil extracts. For Cu and Pb, the effectiveness varied with pyrolysis temperature and phosphate amendment, highlighting the importance of optimization for specific metal contaminants. Biochar generated from elevated pyrolysis temperatures (500 °C) showed an increase in ash content and pH, which improved their ability to retain heavy metals and limit their mobility. These findings suggest that phosphate-amended biochar reduces heavy metal bioavailability, minimizing their entry into the food chain. This supports a sustainable approach for managing hazardous waste and remediating contaminated soils, safeguarding ecosystem health, and mitigating public health risks. Full article
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19 pages, 3457 KiB  
Article
Transcriptome Analysis Revealed the Immune and Metabolic Responses of Grass Carp (Ctenopharyngodon idellus) Under Acute Salinity Stress
by Leshan Ruan, Baocan Wei, Yanlin Liu, Rongfei Mu, Huang Li and Shina Wei
Fishes 2025, 10(8), 380; https://doi.org/10.3390/fishes10080380 - 5 Aug 2025
Viewed by 306
Abstract
Freshwater salinization, an escalating global environmental stressor, poses a significant threat to freshwater biodiversity, including fish communities. This study investigates the grass carp (Ctenopharyngodon idellus), a species with the highest aquaculture output in China, to elucidate the molecular underpinnings of its [...] Read more.
Freshwater salinization, an escalating global environmental stressor, poses a significant threat to freshwater biodiversity, including fish communities. This study investigates the grass carp (Ctenopharyngodon idellus), a species with the highest aquaculture output in China, to elucidate the molecular underpinnings of its physiological adaptations to fluctuating salinity gradients. We used high-throughput mRNA sequencing and differential gene expression profiling to analyze transcriptional dynamics in intestinal and kidney tissues of grass carp exposed to heterogeneous salinity stressors. Concurrent serum biochemical analyses showed salinity stress significantly increased Na+, Cl, and osmolarity, while decreasing lactate and glucose. Salinity stress exerted a profound impact on the global transcriptomic landscape of grass carp. A substantial number of co-regulated differentially expressed genes (DEGs) in kidney and intestinal tissues were enriched in immune and metabolic pathways. Specifically, genes associated with antigen processing and presentation (e.g., cd4-1, calr3b) and apoptosis (e.g., caspase17, pik3ca) exhibited upregulated expression, whereas genes involved in gluconeogenesis/glycolysis (e.g., hk2, pck2) were downregulated. KEGG pathway enrichment analyses revealed that metabolic and cellular structural pathways were predominantly enriched in intestinal tissues, while kidney tissues showed preferential enrichment of immune and apoptotic pathways. Rigorous validation of RNA-seq data via qPCR confirmed the robustness and cross-platform consistency of the findings. This study investigated the core transcriptional and physiological mechanisms regulating grass carp’s response to salinity stress, providing a theoretical foundation for research into grass carp’s resistance to salinity stress and the development of salt-tolerant varieties. Full article
(This article belongs to the Special Issue Adaptation and Response of Fish to Environmental Changes)
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15 pages, 1303 KiB  
Article
Extracellular Vesicle Release from Immune Cells in Cutaneous Leishmaniasis: Modulation by Leishmania (V.) braziliensis and Reversal by Antimonial Therapy
by Vanessa Fernandes de Abreu Costa, Thaize Quiroga Chometon, Katherine Kelda Gomes de Castro, Melissa Silva Gonçalves Ponte, Maria Inês Fernandes Pimentel, Marcelo Rosandiski Lyra, Rienk Nieuwland and Alvaro Luiz Bertho
Pathogens 2025, 14(8), 771; https://doi.org/10.3390/pathogens14080771 - 4 Aug 2025
Viewed by 395
Abstract
Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In [...] Read more.
Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4+, CD8+, and CD14+ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4+ and CD14+ EV were significantly reduced, while CD8+ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article
(This article belongs to the Special Issue Leishmania & Leishmaniasis)
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16 pages, 3236 KiB  
Article
Sulforaphane Prevents Cadmium Chloride-Induced Reproductive Toxicity in Caenorhabditis elegans
by Estefani Yaquelin Hernández-Cruz, Elí Juárez-Peredo, Karla Alejandra Avendaño-Briseño, Jorge Escutia-Martínez, Karla Jaqueline Ramírez-Magaña, Tania Gómez-Sierra and José Pedraza-Chaverri
Oxygen 2025, 5(3), 15; https://doi.org/10.3390/oxygen5030015 - 31 Jul 2025
Viewed by 215
Abstract
Cadmium (Cd) is a highly toxic heavy metal that disrupts development and reproduction, primarily through oxidative stress. In this context, sulforaphane (SFN), an antioxidant compound, may serve as a promising agent to counteract Cd-induced oxidative damage and prevent developmental and reproductive abnormalities. This [...] Read more.
Cadmium (Cd) is a highly toxic heavy metal that disrupts development and reproduction, primarily through oxidative stress. In this context, sulforaphane (SFN), an antioxidant compound, may serve as a promising agent to counteract Cd-induced oxidative damage and prevent developmental and reproductive abnormalities. This study aimed to evaluate the effect of SFN on reproductive toxicity induced by cadmium chloride (CdCl2) in the nematode Caenorhabditis elegans (C. elegans). Five experimental groups were established: (I) Control: no treatment, (II) dimethyl sulfoxide (DMSO): 48 h with 0.01% DMSO, (III) CdCl2: 24 h with 4600 µM CdCl2, (IV) SFN + CdCl2: 24 h with 100 µM SFN followed by 24 h with both SFN and CdCl2, and (V) SFN: 48 h with 100 µM SFN. Co-exposure to SFN and CdCl2 prevented the reduction in the percentage of adult nematodes and increased egg-laying. It also significantly improved hatching rates, allowing more embryos to reach the larval stage, and prevented reductions in body size. However, no effects were observed on glutathione S-transferase-4 (GST-4) levels in the transgenic CL2166 strain. In conclusion, SFN substantially prevents Cd-induced reproductive toxicity in C. elegans. Future studies should investigate the molecular mechanisms by which SFN enhances egg-laying and offspring viability in this model. Full article
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18 pages, 2510 KiB  
Article
The Glutathione Peroxidase Gene Family in Chenopodium quinoa: Genome-Wide Identification, Classification, Gene Expression and Functional Analysis
by Jing Yang, Anna Xu, Kexin An, Lilong Wang, Taiping Luo, Xinyue Yu, Haibo Yin, Shanli Guo and Xia Zhang
Antioxidants 2025, 14(8), 940; https://doi.org/10.3390/antiox14080940 - 30 Jul 2025
Viewed by 288
Abstract
Glutathione peroxidase (GPX) is crucial in mediating plant responses to abiotic stresses. In this study, bioinformatics methods were used to identify the GPX gene family in quinoa. A total of 15 CqGPX genes were identified at the quinoa genome level and conducted preliminary [...] Read more.
Glutathione peroxidase (GPX) is crucial in mediating plant responses to abiotic stresses. In this study, bioinformatics methods were used to identify the GPX gene family in quinoa. A total of 15 CqGPX genes were identified at the quinoa genome level and conducted preliminary analysis on their protein characteristics, chromosome distribution, gene structure, conserved domain structure, cis-acting elements, and expression patterns. Phylogenetic analysis showed that the GPX genes of quinoa, Arabidopsis, soybean, rice, and maize were divided into three groups. Most of the CqGPXs had the three characteristic conserved motifs and other conserved sequences and amino acid residues. Six types of cis-acting elements were identified in the CqGPX gene promoter, with stress and hormone response-related cis-acting elements constituting the two main categories. Additionally, the expression patterns of CqGPX genes across various tissues and their responses to treatments with NaCl, PEG, CdCl2, and H2O2 were also investigated. The qRT-PCR results showed significant differences in the expression levels of the CqGPX genes under stress treatment at different time points. Consistently, the activity of glutathione peroxidase enzymes increased under stresses. Heterologous expression of CqGPX4 and CqGPX15 conferred stress tolerance to E. coli. This study will provide a reference for exploring the function of CqGPX genes. Full article
(This article belongs to the Special Issue Oxidative Stress in Plant Stress and Plant Physiology)
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18 pages, 2652 KiB  
Article
The Use of a Composite of Modified Construction Aggregate and Activated Carbon for the Treatment of Groundwater Contaminated with Heavy Metals and Chlorides
by Katarzyna Pawluk, Marzena Lendo-Siwicka, Grzegorz Wrzesiński, Sylwia Szymanek and Osazuwa Young Osawaru
Materials 2025, 18(15), 3437; https://doi.org/10.3390/ma18153437 - 22 Jul 2025
Viewed by 254
Abstract
The treatment of contaminants from road infrastructure poses significant challenges due to their variable composition and the high concentrations of chloride ions, heavy metals, and oil-derived substances. Traditional methods for protecting groundwater environments are often insufficient. A promising alternative is permeable reactive barrier [...] Read more.
The treatment of contaminants from road infrastructure poses significant challenges due to their variable composition and the high concentrations of chloride ions, heavy metals, and oil-derived substances. Traditional methods for protecting groundwater environments are often insufficient. A promising alternative is permeable reactive barrier (PRB) technology, which utilizes recycled materials and construction waste as reactive components within the treatment zone of the ground. This paper delves into the potential of employing a composite (MIX) consisting of modified construction aggregate (as recycled material) and activated carbon (example of reactive material) to address environmental contamination from a mixture of heavy metals and chloride. The research involved chemical modifications of the road aggregate, activated carbon, and their composite, followed by laboratory tests in glass reactors and non-flow batch tests to evaluate the kinetics and chemical equilibrium of the reactions. The adsorption process was stable and conformed to the pseudo-second-order kinetics and Langmuir, Toth, and Redlich–Peterson isotherm models. Studies using MIX from a heavy metal model solution showed that monolayer adsorption was a key mechanism for removing heavy metals, with strong fits to the Langmuir (R2 > 0.80) and Freundlich models, and optimal efficiencies for Cd and Ni (R2 > 0.90). The best fit, at Cd, Cu, Ni = 0.96, however, was with the Redlich–Peterson isotherm, indicating a mix of physical and chemical adsorption on heterogeneous surfaces. The Toth model was significant for all analytes, fitting Cl and Cd well and Pb and Zn moderately. The modifications made to the composite significantly enhanced its effectiveness in removing the contaminant mixture. The test results demonstrated an average reduction of chloride by 85%, along with substantial removals of heavy metals: lead (Pb) by 90%, cadmium (Cd) by 86%, nickel (Ni) by 85%, copper (Cu) by 81%, and zinc (Zn) by 79%. Further research should focus on the removal of other contaminants and the optimization of magnesium oxide (MgO) dosage. Full article
(This article belongs to the Special Issue Recovered or Recycled Materials for Composites and Other Materials)
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19 pages, 3216 KiB  
Article
The Mechanism of an Fe-Based MOF Material as a Foliar Inhibitor and Its Co-Mitigation Effects on Arsenic and Cadmium Accumulation in Rice Grains
by Tianyu Wang, Hao Cui, Weijie Li, Zhenmao Jiang, Lei Li, Lidan Lei and Shiqiang Wei
Agronomy 2025, 15(7), 1710; https://doi.org/10.3390/agronomy15071710 - 16 Jul 2025
Viewed by 379
Abstract
Arsenic (As) and cadmium (Cd) in rice grains are major global food safety concerns. Iron (Fe) can help reduce both, but current Fe treatments suffer from poor stability, low leaf absorption, and fast soil immobilization, with unclear underlying mechanisms. To address these issues, [...] Read more.
Arsenic (As) and cadmium (Cd) in rice grains are major global food safety concerns. Iron (Fe) can help reduce both, but current Fe treatments suffer from poor stability, low leaf absorption, and fast soil immobilization, with unclear underlying mechanisms. To address these issues, an Fe-based metal–organic framework (MIL-88) was modified with sodium alginate (SA) to form MIL-88@SA. Its stability as a foliar inhibitor and its leaf absorption were tested, and its effects on As and Cd accumulation in rice were compared with those of soluble Fe (FeCl3) and chelating Fe (HA + FeCl3) in a field study on As–Cd co-contaminated rice paddies. Compared with the control, MIL-88@SA outperformed or matched the other Fe treatments. A single foliar spray during the tillering stage increased the rice yield by 19% and reduced the inorganic As and Cd content in the grains by 22.8% and 67.8%, respectively, while the other Fe treatments required two sprays. Its superior performance was attributed to better leaf affinity and thermal stability. Laser ablation inductively coupled plasma–mass spectrometry (LA–ICP–MS) and confocal laser scanning microscopy (CLSM) analyses revealed that Fe improved photosynthesis and alleviated As–Cd stress in leaves, MIL-88@SA promoted As and Cd redistribution, and Fe–Cd co-accumulation in leaf veins enhanced Cd retention in leaves. Full article
(This article belongs to the Topic Effect of Heavy Metals on Plants, 2nd Volume)
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16 pages, 3177 KiB  
Article
Cadmium as the Critical Limiting Factor in the Co-Disposal of Municipal Solid Waste Incineration Fly Ash in Cement Kilns: Implications for Three-Stage Water Washing Efficiency and Safe Dosage Control
by Zhonggen Li, Qingfeng Wang, Li Tang, Liangliang Yang and Guangyi Sun
Toxics 2025, 13(7), 593; https://doi.org/10.3390/toxics13070593 - 15 Jul 2025
Viewed by 419
Abstract
The co-disposal of municipal solid waste incineration fly ash (MSWI-FA) in cement kilns is an effective method for managing incineration by-products in China. However, the presence of heavy metals in MSWI-FA raises environmental concerns. This study analyzed the Cu, Zn, Cd, Pb, Cr, [...] Read more.
The co-disposal of municipal solid waste incineration fly ash (MSWI-FA) in cement kilns is an effective method for managing incineration by-products in China. However, the presence of heavy metals in MSWI-FA raises environmental concerns. This study analyzed the Cu, Zn, Cd, Pb, Cr, and Ni concentrations in MSWI-FA from 11 representative facilities across China and assessed the efficacy of a three-stage water washing process for Cl and heavy metal removal. The results revealed significant regional variations in heavy metal content that were strongly correlated with surface soil levels, with Zn, Pb, and Cu exhibiting the highest concentrations. Elemental correlations, such as Cu-Pb and Zn-Cd synergies and Cd-Ni antagonism, suggest common waste sources and temperature-dependent volatilization during incineration. The washing process (solid–liquid ratio = 1:10) achieved 97.1 ± 2.0% Cl removal, reducing residual Cl to 0.45 ± 0.32%, but demonstrated limited heavy metal elimination (10.28–19.38% efficiency), resulting in elevated concentrations (32.5–60.8% increase) due to 43.4 ± 9.2% mass loss. Notably, the washing effluents exceeded municipal wastewater discharge limits by up to 52-fold for Pb and 38-fold for Cd, underscoring the need for advanced effluent treatment. To mitigate environmental risks, the addition of washed MSWI-FA in cement kilns should be restricted to ≤0.5%, with Cd content prioritized in pre-disposal assessments. This study provides actionable insights for optimizing MSWI-FA co-processing while ensuring compliance with ecological safety standards. Full article
(This article belongs to the Special Issue Distribution and Behavior of Trace Metals in the Environment)
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19 pages, 1773 KiB  
Systematic Review
Immunomodulatory Effects of Anesthetic Techniques in Lung Cancer Surgery: A Systematic Review and Meta-Analysis
by Georgios Konstantis, Ilias Katsadouros, Georgia Tsaousi, Vasileios Grosomanidis and Chryssa Pourzitaki
Medicina 2025, 61(7), 1263; https://doi.org/10.3390/medicina61071263 - 12 Jul 2025
Viewed by 331
Abstract
Background and Objectives: Lung cancer represents one of the principal causes of cancer-associated mortality worldwide. Despite the numerous novel therapeutic agents, surgical resection remains, in many cases, the mainstay treatment. A growing body of evidence indicates that the anesthetic technique of choice [...] Read more.
Background and Objectives: Lung cancer represents one of the principal causes of cancer-associated mortality worldwide. Despite the numerous novel therapeutic agents, surgical resection remains, in many cases, the mainstay treatment. A growing body of evidence indicates that the anesthetic technique of choice contributes to perioperative immunosuppression, thus having an impact on cancer recurrence and prognosis. The aim of this systematic review is to provide a thorough summary of the current literature regarding the modulation of the immune response induced by the various anesthetic techniques that are used in lung cancer surgery, with a particular emphasis on cellular immunity. Materials and Methods: PubMed, Scopus, and the Cochrane databases were systematically searched from November 2023 up to March 2024 to identify randomized controlled trials (RCTs) that met the eligibility criteria. Results: A total of seven RCTs were included. Four of the RCTs compared the administration of general anesthesia alone versus general anesthesia combined with epidural anesthesia. The subsequent meta-analysis showed that the combination of general and epidural anesthesia exerted a positive impact on the cell counts of the CD3+ cells (SMD −0.42, 95% Cl −0.70 to −0.13 24 h postoperatively and SMD −0.86 95% Cl −1.48 to −0.23 72 h postoperatively), the CD4+ cells (SMD −0.41 95% Cl −0.69 to −0.12 at the end of surgery and SMD −0.56 95% Cl −0.85 to −0.27 72 h later), and the CD4+/CD8+ ratio (SMD −0.31 95% Cl −0.59 to −0.02 immediately after surgery, SMD −0.50 95% Cl −0.86 to −0.14 24 h postoperatively, and SMD −0.60 95% Cl −0.89 to −0.31 72 h later). The pooled results regarding CD8+ and NK cell counts were inconclusive. The remaining three studies compared volatile-based anesthesia with total intravenous anesthesia (TIVA). Due to disparities between these studies, qualitative analysis was inconclusive, whereas quantitative analysis was not feasible. Conclusions: The supplementation of general anesthesia with epidural anesthesia favorably impacts CD3+ and CD4+ cell counts, as well as the CD4+/CD8+ ratio. The present results and the effects of anesthetic technique on other immune cells must be consolidated with further high-quality studies. Full article
(This article belongs to the Section Pharmacology)
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28 pages, 5527 KiB  
Article
Oral Metronomic Delivery of Atorvastatin and Docetaxel via Transporter-Targeted Nanoemulsions Enhances Antitumor Efficacy and Immune Modulation in Colon Cancer
by Laxman Subedi, Arjun Dhwoj Bamjan, Susmita Phuyal, Bikram Khadka, Mansingh Chaudhary, Ki-Taek Kim, Ki Hyun Kim, Jung-Hyun Shim, Seung-Sik Cho, Ji Eun Yu and Jin Woo Park
Pharmaceutics 2025, 17(7), 872; https://doi.org/10.3390/pharmaceutics17070872 - 2 Jul 2025
Viewed by 507
Abstract
Background/Objectives: This study aimed to enhance the oral delivery and therapeutic synergy of atorvastatin (AT) and docetaxel (DT) through a metronomic schedule using a transporter-targeted nanoemulsion (NE), with the goal of improving antitumor efficacy and immune modulation. Methods: AT and DT [...] Read more.
Background/Objectives: This study aimed to enhance the oral delivery and therapeutic synergy of atorvastatin (AT) and docetaxel (DT) through a metronomic schedule using a transporter-targeted nanoemulsion (NE), with the goal of improving antitumor efficacy and immune modulation. Methods: AT and DT were co-encapsulated in a NE system (AT/DT-NE#E) incorporating deoxycholic acid–DOTAP (D-TAP), biotin-conjugated phospholipid (Biotin-PE), and d-α-tocopherol polyethylene glycol succinate (TPGS) to exploit bile acid and multivitamin transport pathways and inhibit P-glycoprotein efflux. The optimized NE was characterized physicochemically and evaluated for permeability in artificial membranes and Caco-2/HT29-MTX-E12 monolayers. Pharmacokinetics, tumor suppression, and immune cell infiltration were assessed in vivo using rat and CT26.CL25 mouse models. Results: AT/DT-NE#E showed enhanced permeability of AT and DT by 45.7- and 43.1-fold, respectively, across intestinal cell models and improved oral bioavailability by 118% and 376% compared to free drugs. In vivo, oral metronomic AT/DT-NE#E reduced tumor volume by 65.2%, outperforming intravenous AT/DT. Combination with anti-PD1 therapy achieved a 942% increase in tumor suppression over the control, accompanied by marked increases in tumor-infiltrating CD45+, CD4+CD3+, and CD8+CD3+ T cells. Conclusions: Oral metronomic administration of AT/DT via a dual-transporter-targeted NE significantly improves drug absorption, tumor inhibition, and immune response. This strategy presents a safe and effective approach for colon cancer therapy, particularly when combined with immunotherapy. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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13 pages, 2581 KiB  
Article
Triazine Calixarene as a Dual-Channel Chemosensor for the Reversible Detection of Cu2+ and I Ions via Water Content Modulation
by Fuyong Wu, Long Chen, Mei Yu, Liang Zhao, Lu Jiang, Tianzhu Shi, Ju Guo, Huayan Zheng, Ruixiao Wang and Mingrui Liao
Molecules 2025, 30(13), 2815; https://doi.org/10.3390/molecules30132815 - 30 Jun 2025
Viewed by 369
Abstract
Rationally designing and synthesizing chemosensors capable of simultaneously detecting both anions and cations via water content modulation is challenging. In this study, we synthesized and characterized a novel triazine calixarene derivative-based iodide and copper ion-selective fluorescent “turn-off” sensor. This dual-channeled fluorescent probe is [...] Read more.
Rationally designing and synthesizing chemosensors capable of simultaneously detecting both anions and cations via water content modulation is challenging. In this study, we synthesized and characterized a novel triazine calixarene derivative-based iodide and copper ion-selective fluorescent “turn-off” sensor. This dual-channeled fluorescent probe is able to recognize Cu2+ and I ions simultaneously in aqueous systems. The fluorescent sensor s4 was synthesized by displacement reaction of acridine with 1, 3-bis (dichloro-mono-triazinoxy) benzene in acetonitrile. Mass spectrometry (MS), UV-vis, and fluorescence spectra were acquired to characterize the fluorescence response of s4 to different cations and anions, while infrared (IR) spectroscopy and isothermal titration calorimetry (ITC) were employed to study the underlying selectivity mechanism of s4 to Cu2+ and I. In detail, s4 displayed extremely high sensitivity to Cu2+ with over 80% fluorescence decrement caused by the paramagnetic nature of Cu2+ in the aqueous media. The reversible fluorescence response to Cu2+ and the responses to Cu2+ in the solution of other potential interferent cations, such as Li+, Na+, K+, Ca2+, Cd2+, Zn2+, Sr2+, Ni2+, Co2+ were also investigated. Probe s4 also exhibited very good fluorescence selectivity to iodide ions under various anion (F, Cl, Br, NO3, HSO4, ClO4, PF6, AcO, H2PO4) interferences. In addition to the fluorescent response to I, s4 showed a highly selective naked-eye-detectable color change from colorless to yellow with the other tested anions. Full article
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16 pages, 6251 KiB  
Article
Removal of HF via CaCl2-Modified EAF Slag: A Waste-Derived Sorbent Approach
by Go-eun Kim, Seong-ho Jang and Young-chae Song
Water 2025, 17(13), 1919; https://doi.org/10.3390/w17131919 - 27 Jun 2025
Viewed by 561
Abstract
This study evaluates CaCl2-modified electric arc furnace (EAF) slag for fluoride removal from synthetic hydrofluoric acid (HF) wastewater. Adsorption performance was assessed under different particle sizes (850 μm–1.7 mm, 250–850 μm, and <250 μm), temperatures (25–45 °C), and initial pH values [...] Read more.
This study evaluates CaCl2-modified electric arc furnace (EAF) slag for fluoride removal from synthetic hydrofluoric acid (HF) wastewater. Adsorption performance was assessed under different particle sizes (850 μm–1.7 mm, 250–850 μm, and <250 μm), temperatures (25–45 °C), and initial pH values (2–11), using oxidized (EOS) and reduced (ERS) slags in raw and modified (C1, C2) forms. Characterization included isotherm modeling (Langmuir and Freundlich), X-ray diffraction (XRD), and inductively coupled plasma mass spectrometry (ICP-MS). The CaCl2-modified slags (particularly EOS-C2 and ERS-C2) demonstrated stable performance under all conditions. ERS-C2 achieved the maximum adsorption capacity of 16.13 mg/g at 600 mg F/L. EOS-C2 maintained capacities above 8.0 mg/g across pH 2–11, whereas unmodified slag showed a decline in performance above pH 5, with residual concentrations exceeding 250 mg F/L and capacities dropping to 1.14–2.14 mg/g. XRD analysis indicated increased amorphization and enhancement of dicalcium silicate and brownmillerite phases after modification. Isotherm fitting showed better agreement with the Freundlich model, suggesting multilayer adsorption. Leaching tests confirmed that Cr, Cu, and As concentrations were within safe limits, while Pb and Cd were not detected. These results demonstrate the strong potential of CaCl2-modified EAF slag as an efficient, pH-stable, and environmentally safe adsorbent for treating HF-containing industrial wastewater. Full article
(This article belongs to the Section Wastewater Treatment and Reuse)
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16 pages, 2127 KiB  
Article
Residual Chlorine Interaction with Microelements in Plants Applied for Phytoremediation in Rain Gardens
by Ieva Andriulaityte, Marina Valentukeviciene, Viktoras Chadysas and Antonina Kalinichenko
Plants 2025, 14(13), 1957; https://doi.org/10.3390/plants14131957 - 26 Jun 2025
Viewed by 491
Abstract
Stormwater pollution from residual chlorine after outdoor disinfection with sodium hypochlorite is an increasing environmental challenge due to its potential negative impact on aquatic ecosystems. Even at low concentrations, residual chlorine can disrupt the stability of water ecosystems. In this regard, stormwater treatment [...] Read more.
Stormwater pollution from residual chlorine after outdoor disinfection with sodium hypochlorite is an increasing environmental challenge due to its potential negative impact on aquatic ecosystems. Even at low concentrations, residual chlorine can disrupt the stability of water ecosystems. In this regard, stormwater treatment requires innovative and green solutions such as green infrastructure (rain gardens) using the plant phytoremediation technique to reduce the amount of residual chlorine. This study explores the interactions between residual chlorine retained by plants in a rain garden and different microelements. Selected plants were analyzed via spectroscopy, and possible interactions with elements such as chlorine (Cl), phosphorus (P), zinc (Zn), iron (Fe), calcium (Ca), potassium (K), nickel (Ni), silicon (Si), manganese (Mn), magnesium (Mg), chromium (Cr), and cadmium (Cd) were determined using Python-based analysis. Chlorine presented significant positive correlations with cadmium (0.39–0.53) and potassium (0.51–0.55), while negative correlations were found between silicon and chlorine (−0.48–−0.54) and chlorine and iron (−0.45–−0.51). The correlations between chlorine and microelements suggest both common uptake mechanisms and mutual interactions. These results provide a better understanding of the behavior of chlorine in rain gardens and its interactions with other materials, which is especially valuable for designing green infrastructure. This research can help to develop sustainable solutions that reduce environmental pollution and strengthen urban adaptation to climate change. Full article
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