Search Results (51,381)

Viper bites are medical emergencies that can develop into serious clinical complications and can endanger the life of the paediatric patient. This observational retrospective study analyses 24 cases of viper bites involving paediatric patients (<18 years) encountered over 10 years (2016–2025) in the emergency department of Saint Mary Emergency Hospital of Iasi, Romania, with a focus on those requiring specialised surgical monitoring. Sociodemographic factors, toxicity, and surgical management of snakebites were analysed. In 83.33% cases, viper bites were found on the lower limb. The retrospective study was completed through an in-depth analysis of two representative cases, with a particular focus on the evolution up to compartment syndrome. Of the 24 cases presented in the Emergency Department, one was a rare and severe case, which evolved into compartment syndrome and required fasciotomy to save the limb in the Plastic Surgical Department. Another one, with the bite localised at the upper limb, had perilesional oedema, without skin colour changes or secretions, preservation of joint contours, and normal nail colouration. Both were analysed and described in detail with all available data (images, investigations, etc.) to highlight pathophysiological and therapeutic aspects. Appropriate, multidisciplinary treatment considerably improves the functional prognosis of patients with viper bites; administration of antivenom and selective fasciotomy contribute to successful outcomes. The study emphasises that viper bites in children remain a public health problem in Romania and require prompt and multidisciplinary treatment. Full article

Background: Stenotrophomonas maltophilia is a multidrug-resistant pathogen with limited therapeutic options that predominantly affects critically ill and immunocompromised patients. Trimethoprim–sulfamethoxazole (TMP/SMX) remains the conventional first-line therapy; however, emerging resistance and toxicity concerns necessitate alternative regimens. This study represents, to our knowledge, the first network meta-analysis (NMA) comparing the efficacy and safety of clearly defined monotherapy and combination antibiotic regimens for S. maltophilia infections. Materials and methods: A systematic search of PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov (inception to January 2026) identified eligible randomized-controlled studies and retrospective studies. Data were analyzed using a frequentist random-effects NMA with TMP/SMX as the reference. Evaluated regimens included TMP/SMX, fluoroquinolone (FQ), minocycline (MIN), TMP/SMX + FQ, TMP/SMX + MIN, FQ + MIN and FQ + other. Primary and secondary outcomes were all-cause mortality, clinical cure, and adverse effects. Results: Thirteen retrospective studies encompassing 2980 patients were included. Using TMP/SMX as the reference, network meta-analysis demonstrated heterogeneity in all-cause mortality across antimicrobial regimens. FQ and MIN monotherapies were associated with lower odds of mortality (effect sizes: 0.65, 95% CI: 0.49–0.85 and 0.50, 95% CI: 0.28–0.90), whereas combination therapy with TMP/SMX plus FQ was associated with higher mortality (effect size: 2.93, 95% CI: 1.18–7.31). Treatment ranking based on effect sizes suggested more favorable mortality profiles for MIN and FQ regimsens. No significant differences were observed in clinical cure, while FQ was associated with a lower incidence of adverse effects compared with TMP/SMX. Conclusions: This network meta-analysis suggests that FQ and MIN monotherapies may be associated with more favorable survival and tolerability compared with TMP/SMX monotherapy. No clear differences were observed for combination therapy relative to other active monotherapy options. Prospective randomized studies are required to validate these observations and to better inform the management of S. maltophilia infections. Full article

Intranasal drug delivery represents a transformative “backdoor” to the brain, bypassing the blood–brain barrier (BBB) that bars 98% of small molecules and nearly all large biopharmaceuticals. By harnessing the unique anatomy of the olfactory and trigeminal nerves, therapeutics can travel directly from the nasal cavity to the central nervous system, achieving therapeutic concentrations without the systemic toxicity of traditional routes. Clinical and preclinical evidence highlight the efficacy of intranasal insulin (INI) in treating Alzheimer’s disease (AD) and delirium, with studies showing significant improvements in cognitive scores and reduced hospital stays (7.9 vs. 12.9 days; p = 0.014). Additionally, other peptides can be administered intranasally like oxytocin, neuropeptide Y, and novel metabolic modulators for neuroprotection and affective disorders (AD, autism, Down syndrome). Despite these promises, critical translational gaps remain, including anatomical differences between macrosmatic rodents and microsmatic humans, and significant sex-based dosing dimorphism. The ease of intranasal administration introduces profound bioethical dilemmas regarding neuroenhancement, authenticity, and informed consent in vulnerable populations. The current literature concludes that realizing the full potential of nose-to-brain (N2B) therapy requires a commitment to precision medicine, utilizing specialized delivery devices and objective biomarkers to ensure safe and equitable clinical application. Full article

The increasing prevalence of antimicrobial resistance, especially in methicillin-resistant Staphylococcus aureus (MRSA), underscores the need for alternative therapies from natural sources. This study investigated the chemical composition, antibacterial activity, and gene expression modulation of Melaleuca cajuputi essential oils. Gas chromatography–mass spectrometry (GC-MS) identified 91 compounds, with naphthalene (23.90%), guaiol (12.92%), caryophyllene oxide (9.69%), D-limonene 98% (8.59%), and gamma terpinene (7.54%) among the most abundant. In Silico molecular docking against MRSA virulence proteins revealed that alloaromadendrene had the strongest binding to toxic shock syndrome toxin-1 (TSST-1) (−7.948 kcal/mol), suggesting high inhibitory potential, while cyclohexane showed weak binding with staphylococcal enterotoxin A (SEA) (−3.532 kcal/mol). Antibacterial assays demonstrated concentration-dependent inhibition, with the zones ranging from 6.33 ± 0.33 mm to 16.67 ± 0.88 mm. MIC and MBC values ranged from 1.56 to 12.5% and 3.13 to 25%, respectively, with most isolates showing bactericidal effects (MBC/MIC ≤ 2). Gene expression analysis of MRSA isolate 4 indicated that sea was moderately upregulated (FC = 1.44), while sec remained unchanged (FC = 1.02). In contrast, fnbA (FC = 0.72), seb (FC = 0.33), and mecA (FC = 0.23) genes were downregulated, and the tsst-1 gene (FC = 0.05) was nearly silent. These findings highlight M. cajuputi essential oils as a promising candidate with both antibacterial efficacy and regulatory effects on MRSA virulence genes. Full article

The modern development of the energy and metallurgy industries is accompanied by the increasing use of coal in the form of fuel and raw material. However, at the same time, urgent issues are arising concerning assessments of its radiological and environmental safety. Coal and ashes accumulate natural radionuclides (such as thorium, uranium, and potassium-40), and toxic and rare earth elements (REEs) that are capable of migrating into the environment during the processes of production, burning and ash disposal. Special attention has recently been paid to rare earth elements that are of economic value as critical metals for sophisticated technologies, but these can pose environmental risks. Their presence in coal is becoming an increasingly relevant issue for cross-disciplinary research, at the intersection of geochemistry, radioecology and the sustainable use of natural resources. Moreover, issues regarding the radiological safety of coal deposits and their derivative products are especially crucial for Kazakhstan, Russia, China and other countries with developed coal production industries. Studies demonstrate that ash and slag of thermal power plants can comprise increased concentrations of natural radionuclides that can accumulate in soil, water and the environment. Therefore, the study of rare earth, toxic and radioactive element contents in coal using nuclear analytical methods is of high practical and environmental significance, especially in terms of assessing radiation load on the environment, designing control measures and ash disposal, and the prospect of the selective extraction of REEs from the coals. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which no disease-modifying therapy that halts or substantially slows disease progression is currently available. Although antibody therapies targeting amyloid β (Aβ) have recently received FDA approval, their high cost, limited efficacy, and potential adverse effects highlight the need for alternative solutions. Therefore, the development of low-molecular-weight compounds capable of reducing toxic Aβ aggregates is of considerable interest. In this study, we investigated the effects of 2,3,4-trihydroxybenzophenone (THB) on the inhibition and disassembly of Aβ_1–42 aggregates through in vitro and in vivo experiments. Methods: In vitro assays were performed to evaluate the effects of THB on Aβ_1–42 aggregation and fibril disassembly. Cell viability assays and hippocampal slice electrophysiology were conducted to assess neurotoxicity and synaptic function. In vivo effects were examined in Aβ_1–42 aggregate-injected mice and in 5 Familial AD mutations (5XFAD) mice using behavioral, histological, and electrophysiological analyses. Results: THB inhibited Aβ_1–42 aggregation in a concentration-dependent manner and promoted the disassembly of preformed fibrils. THB attenuated Aβ_1–42-induced Neuro2a cell death and restored Aβ_1–42 aggregate-associated long-term potentiation (LTP) deficits in hippocampal slices. In Aβ_1–42 aggregate-injected and 5XFAD mice, THB reduced amyloid pathology and neuroinflammatory markers and improved synaptic function and memory performance. Conclusions: These findings suggest that THB modulates pathogenic Aβ_1–42 assemblies and provides a structural basis for the development of small-molecule modulators of Aβ_1–42 aggregation with potential preventive or disease-modifying applications in AD. Full article

Fluopyram is a widely used nematicide with a growing number of varieties registered both domestically and overseas. However, its absorption, transportation, and metabolism behaviors in plants have not been fully elucidated, thus hindering comprehensive assessment of the risks associated with its use. This study investigated the plant uptake, distribution, and metabolic behavior of fluopyram through 168 h hydroponic experiments. Fluopyram was easily absorbed by the roots of the tested crops, and almost 90.5% and 70.9% of fluopyram was transformed in cucumber and tomato, respectively, leading to the tentative identification of 16 metabolites using Quadrupole Time-of-Flight mass spectrometry. The metabolic reactions involved were hydroxylation, hydroxylation–dechlorination, dehydrogenation, dechlorination, and glucuronidation conjugation. Most metabolites were detected in leaves, suggesting that they have considerable potential to accumulate in the upper parts, even the edible parts. Model prediction indicated that fluopyram and high-toxicity metabolites (M430A, M412C) pose significant risks to aquatic ecosystems across trophic levels, while M574A and M574B showed reduced toxicity due to glucuronidation conjugation. These findings deepen our understanding of the behavioral characteristics of fluopyram within plants, and serve as an important reference for comprehensively assessing its risks. Full article

Rationale: Radium-223 dichloride (²²³RaCl₂) is an FDA-approved alpha-emitting radiopharmaceutical that targets bone metastases in metastatic castration-resistant prostate cancer (mCRPC). This study investigates the therapeutic and immunological effects of combining ²²³RaCl₂ with immune checkpoint inhibitors (ICIs) in a clinically relevant, immunocompetent murine model of prostate cancer bone metastasis. Methods: Luciferase-expressing MyC-CaP prostate cancer cells were implanted intratibially into FVB mice to establish bone metastases. Mice were treated with escalating doses of ²²³RaCl₂ (0.04–0.27 µCi) alone or a single dose combined with anti-CTLA-4 and anti-PD-L1 ICIs. Tumor growth was monitored using bioluminescence imaging. Micro-CT, alpha camera imaging, histology, and qPCR were used to assess bone remodeling, radiopharmaceutical distribution, immune infiltration, and gene expression. Ex vivo biodistribution and blood analyses quantified tissue uptake and toxicity. Results: Escalating doses of ²²³RaCl₂ did not significantly inhibit tumor growth or improve survival. Biodistribution and imaging showed preferential localization of ²²³RaCl₂ to tumor-adjacent bone, with minimal signal in isolated tumor tissue. Immunohistochemistry revealed increased CD4⁺ and CD8α⁺ T-cell infiltration in regions of high γH2AX expression, indicating localized immune modulation. However, combination therapy with ICIs did not enhance tumor control or immune infiltration beyond monotherapy. qPCR demonstrated significant upregulation of Mhc1 only in the combination group, suggesting localized immune activation. Toxicity profiles remained acceptable. Conclusions: ²²³RaCl₂ localizes primarily to bone surfaces, limiting direct cytotoxic and immunomodulatory effects within the tumor microenvironment. While combination with ICIs did not improve efficacy, these findings provide a platform for studying spatial dose distribution and support future development of tumor-targeted alpha therapies to potentiate immunotherapy in mCRPC. Full article

The environmental degradation of plastics results not only in their mechanical fragmentation into microplastics (MPs), but also in polymer main-chain scission processes, causing continuous leaching and/or volatilization of low-molecular-weight species, often characterized by a hazardous profile. In this study, we investigated the hydrophilic photooxidation products (HyPOPs) generated upon UV irradiation of polystyrene (PS) and their transformation catalyzed by the enzyme laccase from the fungus Trametes versicolor. Through a series of enzymatic tests, the enzyme was found to promote coupling and conjugation reactions of HyPOPs into poorly soluble compounds mimicking natural humic acids. The enzymatic activity of laccase was studied under different experimental conditions to simulate those found in environmental matrices. Due to their oligomeric nature, these humic acid-like products of metabolic transformation by the fungal laccase are here nicknamed “mycoplastics” (i.e., polymers from fungi). This enzymatic biodegradation and biotransformation of xenobiotic HyPOPs highlights the role of specific enzymes as biological tools for environmental self-repair of polluted ecosystems. Moreover, it opens new perspectives for remediation strategies targeting elusive micro- and nanoplastics and their continuously generated hazardous molecular degradation by-products. Humic acid-like products resulting from laccase conversion of HyPOPs could contribute to the rehabilitation of contaminated sites by promoting the removal of toxic contaminants from soil and water. Full article

Plastics are highly persistent materials, and their environmental degradation can potentially exacerbate, rather than alleviate, pollution. The degradation of plastic materials releases toxic monomers and additives, such as bisphenol A (BPA), styrene, and dioxins, which are more reactive, harmful, and persistent than intact plastics. With half-lives ranging from weeks to decades, they bioaccumulate in food chains, disrupt ecosystems, and contribute to endocrine disruption and mutagenicity. Natural degradation pathways, like microbial metabolism and photodegradation, are slow and incomplete, often leaving toxic intermediates such as microplastics. Artificial strategies, including bioremediation and advanced oxidation processes (AOPs), show potential to address the problems of plastic pollution but face additional challenges like secondary pollution and scalability. Sustainable alternatives, including bioplastics and renewable non-plastic substitutes, present promising solutions. However, their widespread adoption is hindered by challenges such as high production costs and the need for specific conditions to facilitate degradation, necessitating further research and development. A combined approach of reducing plastic production, advancing recycling, and implementing effective remediation strategies is critical to mitigating plastic pollution’s long-term impacts on ecosystems, biodiversity, and human health. This review provides a critical analysis of the current understanding of plastic degradation processes and the toxic byproducts they generate. It highlights the paradox wherein increased degradability may exacerbate environmental hazards. Additionally, the review assesses innovative, eco-friendly alternatives designed to mitigate plastic pollution. Full article

Mycoplasma pneumoniae (M. pneumoniae) is the crucial factor of global acquired respiratory infections. Currently, there are no specific disease modification treatments or vaccines available, and the vaccine development for this pathogen lags behind due to the complexity and variability of its antigens. A novel vaccine with broad-spectrum characteristics is essential to provide comprehensive protection against continuously evolving wild-type strains. Here, a broad-spectrum muti-epitope vaccine against M. pneumoniae had been designed through immunoinformatics methods. To ensure its broad-spectrum, we generated consistent sequences from all the antigen proteins of different strains, and then identified potential T cell epitopes. The multi-epitope vaccine (MEV) of M. pneumoniae incorporated 16 CTLs and 7 HTLs from the HMW1–3 and p1 adhesin proteins, which comprised 458 amino acids with adjuvant. The vaccine evaluation showed that the MEV had ideal physicochemical properties, high antigenicity, high immunogenicity, and was non-toxic. Furthermore, there was a strong and stable binding interaction between this vaccine and the toll-like receptors, which could be supported by the normal mode analysis. Finally, codon optimization resulted in the optimal GC content and higher CAI value. The vaccine candidate is expected to induce strong cellular immune responses and may provide protective immunity against the pathogen. We provided a novel in silico vaccine design strategy for vaccine design, which could provide a technical framework for the development of vaccines against other pathogens. Full article

Candida auris is a critical emerging pathogen of high priority due to its ability to develop multidrug resistance to various antifungals. Given the increase in cases associated with C. auris, it is essential to evaluate new candidates with antifungal potential. In this context, flavonoids represent a promising source for the development of new therapeutic alternatives. In this study eleven flavonoids were evaluated for their antifungal activity against C. auris strains from clades III and IV. The flavonoids showed dose-dependent inhibition of C. auris growth. Toxicity tests were conducted using the in vivo Tenebrio molitor model. The flavonoids exhibited toxicity levels either comparable to or lower than reference antifungals. Also, the study examined the ability of the flavonoids to inhibit efflux pumps. Some of the flavonoids (quercetin, fisetin, hesperetin, luteolin and apigenin) reduced efflux pump activity, which is an important feature since these pumps actively expel antifungal drugs from the cell, reducing the drug’s effectiveness. This suggests that the flavonoids might inhibit efflux pump activity, potentially enhancing the efficacy of antifungal treatments. The study supports the potential of flavonoids as new therapeutic agents for C. auris. Since they target efflux pumps, which are a significant mechanism of resistance in C. auris, flavonoids could be used either alone or in combination with existing antifungals to improve treatment outcomes. Full article

Emodin, a trihydroxy-methyl anthraquinone abundant in rhubarb, Polygonum species, and other medicinal plants, exemplifies the therapeutic potential and translational complexity of the broader anthraquinone scaffold. Anthraquinone derivatives have demonstrated antiproliferative, anti-inflammatory, metabolic, cardiovascular, antifibrotic, and immunomodulatory effects, consistently reported across diverse preclinical models, targeting pathways such as NF-κB, PI3K/AKT, MAPKs, AMPK, PPARs, NLRP3, and ferroptosis-related axes. Despite strong preclinical efficacy, clinical development has been limited by unfavorable absorption, distribution, metabolism, and excretion (ADME) characteristics, including poor aqueous solubility, extensive first-pass glucuronidation, and active efflux via intestinal and hepatic transporters. These features result in low and variable systemic exposure, while high local concentrations, particularly in the gastrointestinal tract, contribute to context-dependent toxicity signals that complicate risk assessment. The present review integrates pharmacological, toxicological, and formulation-focused evidence to provide a unified assessment of emodin and the anthraquinone scaffold. Particular emphasis is placed on bidirectional, dose- and context-dependent effects on the liver and kidney; the modulation of cytochrome P450 enzymes, UGTs, and transporters; and emerging preclinical formulation strategies that aim to decouple intrinsic bioactivity from pharmacokinetic limitations. Full article

Research on heterotrophic bioflocs is extensive, whereas investigations into autotrophic bioflocs remain limited. This study established an in situ autotrophic biofloc (ABF) system for intensive Pacific white shrimp (Penaeus vannamei) farming, aiming for zero water exchange and optimized water quality. A 120-day indoor experiment tested three stocking densities (300 (T1), 250 (T2), and 200 shrimp per m³ (T3)) with no water exchange. Water quality was monitored every two days, and bacterial communities were analyzed on days 10 and 70. The results indicated that ABF maturation was achieved by day 70 across all treatments, marked by three key indicators: (1) synchronous declines in nitrite and nitrate concentrations; (2) concurrent decreases in pH and total alkalinity approaching maturation; and (3) sustained high nitrogen removal efficiency (nitrite < 0.7 mg/L, ammonia < 0.6 mg/L). All density groups displayed similar patterns in both water quality dynamics and microbial community evolution. Bacterial analysis revealed that dominant genera such as Ruegeria, Bacillus, Muricauda, SM1A02, and Nitrospira played critical roles in toxic nitrogen removal, while pathogenic Klebsiella and Vibrio significantly decreased post-maturation. Heterotrophic nitrification and aerobic denitrification microorganisms (HNADMs) were identified as potentially responsible for nitrite accumulation. Nitrite accumulation was found in all groups. T2 and T3 achieved satisfactory breeding performance despite pre-maturation nitrate peaks exceeding 40 mg/L, whereas T1 suffered a low survival rate (27.47%) due to severe nitrite accumulation (>50 mg/L). A biofloc volume (BFV) of 4–8 mL/L effectively managed daily feed inputs of 75–110 g/m³. These findings lay a theoretical and technical foundation for the application of in situ ABF cultivation in intensive farming and enhance the sustainability of aquaculture. Full article

Red blood cells represent a widely used cellular model in cytotoxicity studies, particularly in hemocompatibility assessments. As enucleated cells, which are abundant and easily accessible in both humans and animals, red blood cells allow for rapid, reproducible, and low-cost evaluation of the toxicity of bioactive compounds, whether natural, synthetic, or nanoparticulate. From a functional perspective, the red blood cell membrane is highly sensitive to physical and chemical environmental changes (osmolarity, temperature, pH, and the presence of oxidizing agents). This sensitivity makes red blood cells an effective biosensor for detecting membrane damage, hemolysis, oxidative stress, methemoglobin formation, and aggregation processes. Therefore, in vitro tests using red blood cells allow for the preliminary evaluation in preclinical development, particularly for the early screening of cytotoxicity, membrane-disruptive effects, and hemocompatibility of small molecules, nanomaterials, and blood-contacting biomaterials. These techniques include hemocompatibility tests, evaluation of oxidative and osmotic damage, and evaluation of erythrocyte aggregation and function. However, the use of red blood cells as a cytotoxicity model also has significant limitations. As anucleate cells, erythrocytes lack organelles such as nuclei, mitochondria, or lysosomes, which prevents the evaluation of their effects on key intracellular processes such as protein synthesis, cell signaling, apoptosis, or endoplasmic reticulum stress. This lack of cellular complexity limits their usefulness as a sole model in studies of systemic toxicity or tissue-specific cytotoxicity. These tools offer an effective preliminary approach to anticipating risks in biomedical and pharmacological research. Full article