Search Results (2,252)

Internal combustion engine vehicles damage the environment and public health by emitting toxic fumes, such as CO₂ or CO and other trace compounds. The use of electric cars helps to reduce the emission of pollutants into the environment due to the use of batteries with no direct and local emissions. However, accidents of battery electric vehicles pose new challenges, such as thermal runaway. Such accidents can be serious and, in some cases, may result in uncontrolled overheating that causes the battery pack to spontaneously ignite. In particular, the most dangerous vehicles are heavy goods vehicles (HGVs), as they release a large amount of energy that generate high temperatures, poor visibility, and respiratory damage. This study aims to determine the potential consequences of large BEV fires in road tunnels using computational fluid dynamics (CFD). Furthermore, a comparison between a BEV and an ICEV fire shows the differences related to the thermal and the toxic impact. Furthermore, the adoption of a longitudinal ventilation system in the tunnel helped to mitigate the BEV fire risk, keeping a safer environment for tunnel users and rescue services through adequate smoke control. Full article

Background/Objectives: The heterogeneity of cancer disease and the frequent ineffectiveness and resistance observed with currently available treatments highlight the importance of developing new antitumor therapies. The properties of gold nanoparticles, such as their photon-energy heating, are attractive for oncology therapy; this can be effective and localized. The combination of chemotherapy and hyperthermia is promising. Our aim was to evaluate the combination therapy of photon hyperthermia with 5-fluorouracil (5-FU) both in vitro and in vivo. Methods: This study evaluated the antitumor efficacy of a combined chemo-photothermal therapy using 5-fluorouracil (5-FU) and branched gold nanoshells (BGNSs) in a colorectal cancer model. BGNSs were synthesized via a seed-mediated method and characterized by electron microscopy and UV–vis spectroscopy, revealing an average diameter of 126.3 nm and a plasmon resonance peak at 800 nm, suitable for near-infrared (NIR) photothermal applications. In vitro assays using SW620-GFP colon cancer cells demonstrated a ≥90% reduction in cell viability after 24 h of combined treatment with 5-FU and BGNS under NIR irradiation. In vivo, xenograft-bearing nude mice received weekly intratumoral administrations of the combined therapy for four weeks. The group treated with 5-FU + BGNS + NIR exhibited a final tumor volume of 0.4 mm³ on day 28, compared to 1010 mm³ in the control group, corresponding to a tumor growth inhibition (TGI) of 100.74% (p < 0.001), which indicates not only complete inhibition of tumor growth but also regression below the initial tumor volume. Thermographic imaging confirmed that localized hyperthermia reached 45 ± 0.5 °C at the tumor site. Results: These findings suggest that the combination of 5-FU and BGNS-mediated hyperthermia may offer a promising strategy for enhancing therapeutic outcomes in patients with colorectal cancer while potentially minimizing systemic toxicity. Conclusions: This study highlights the potential of integrating nanotechnology with conventional chemotherapy for more effective and targeted cancer treatment. Full article

We adapt previously developed conceptual and numerical models of ciguateric food chains on the Great Barrier Reef, Australia, to model the bioaccumulation of ciguatoxins (CTXs) in parrotfish, the simplest food chain with only two trophic levels. Our model indicates that relatively low (1 cell/cm²) densities of Gambierdiscus/Fukuyoa species (hereafter collectively referred to as Gambierdiscus) producing known concentrations of CTX are unlikely to be a risk of producing ciguateric fishes on the Great Barrier Reef unless CTX can accumulate and be retained in parrotfish over many months. Cell densities on turf algae equivalent to 10 Gambierdiscus/cm² producing known maximum concentrations of Pacific-CTX-4 (0.6 pg P-CTX-4/cell) are more difficult to assess but could be a risk. This cell density may be a higher risk for parrotfish than we previously suggested for production of ciguateric groupers (third-trophic-level predators) since second-trophic-level fishes can accumulate CTX loads without the subsequent losses that occur between trophic levels. Our analysis suggests that the ratios of parrotfish length-to-area grazed and weight-to-area grazed scale differently (allometrically), where the area grazed is a proxy for the number of Gambierdiscus consumed and hence proportional to toxin accumulation. Such scaling can help explain fish size–toxicity relationships within and between trophic levels for ciguateric fishes. Our modelling reveals that CTX bioaccumulates but does not necessarily biomagnify in food chains, with the relative enrichment and depletion rates of CTX varying with fish size and/or trophic level through an interplay of local and regional food chain influences. Our numerical model for the bioaccumulation and transfer of CTX across food chains helps conceptualize the development of ciguateric fishes by comparing scenarios that reveal limiting steps in producing ciguateric fish and focuses attention on the relative contributions from each part of the food chain rather than only on single components, such as CTX production. Full article

Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in clinical analyses. This study aimed to evaluate clinical outcomes and toxicity of SBRT for pulmonary oligometastases in octogenarians. Methods: This retrospective, single-centre analysis included 34 patients aged ≥ 80 years treated with SBRT for histologically confirmed pulmonary oligometastases between 2010 and 2024. Results: A total of 46 pulmonary metastases were treated with curative intent using fractionation schemes of 3 × 15 Gy, 6 × 8 Gy, or 10 × 6 Gy. Median biologically effective dose (BED10) was 112.5 Gy. Follow-up included regular CT imaging and toxicity assessment according to CTCAE. With a median follow-up of 22.6 months, 1-, 2-, and 3-year local control (LC) rates were 95.2%, 95.2%, and 90.2%, respectively. Median overall survival (OS) was 46.6 months, with 1-, 2-, and 3-year OS rates of 78.4%, 71.4%, and 59.5%. Progression-free survival (PFS) at 1, 2, and 3 years was 63.4%, 51.6%, and 47.3%, respectively. No grade ≥ 3 toxicities were observed. Grade 2 pneumonitis and dermatitis occurred in 2.9% each and were well managed. Asymptomatic rib fractures were detected in 5.9% of patients. No significant predictors for LC, PFS, or OS were identified in univariate analysis. Conclusions: SBRT for pulmonary oligometastases in patients ≥ 80 years is feasible, safe, and effective. High local control, favourable cancer-specific survival, and minimal toxicity support its use as a curative-intent treatment in this growing patient population. These findings contribute important site- and age-specific evidence and support the inclusion of very elderly patients in future prospective SBRT trials. Full article

Background/Objectives: Treatment of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer involves neoadjuvant chemotherapy followed by complex surgery, posing significant risks of toxicity, complications, and changes in quality of life (QoL). This study aims to investigate the impact of neoadjuvant chemotherapy followed by resection on overall survival (OS) and QoL. Methods: Consecutive patients with BRPC and LAPC included in a population-based study (NORPACT-2) from January 2018 to December 2020 were reviewed. Results: A total of 54 patients (BRPC; n = 43, LAPC; n = 11) underwent neoadjuvant chemotherapy followed by pancreatectomy. The majority (66.7%) received (m)FOLFIRINOX. Forty-six (85.2%) patients underwent pancreatoduodenectomy. Vascular resection was performed in 32 (59.3%) patients. Fourteen (25.9%) patients experienced major complications. The majority of the resected specimens demonstrated T2 (63%), N+ (79.6%), and R1 (85.2%) status. Median OS was 31 (CI 24.7–37.3) months. In multivariate analysis, only CAP 3 (p = 0.035) predicted worse survival. Forty (74.1%) patients experienced recurrence. Global QoL (p = 0.031), social and role functioning (p = 0.024, p = 0.031), improved three months after surgery. Pain (p = 0.042), dyspnea (p = 0.004), appetite loss (p = 0.028), and diarrhea (p = 0.007) improved post-resection. Conclusions: Patients with BRPC and LAPC undergoing neoadjuvant chemotherapy and resection have survival comparable to primary resectable pancreatic cancer. Postoperative morbidity was acceptable, and QoL recovered post-surgery. CAP grade was the only independent negative prognostic factor. Full article

Background/Objectives: Limited robust data support the use of antibiotic combinations in the treatment of orthopedic infections. However, in certain situations, the combination of antibiotics seems to be beneficial. This review aims to outline the circumstances under which a combination of antibiotics may be utilized in the treatment of orthopedic infections. Methods: We reviewed the existing guidelines on orthopedic infections and focused on situations where antibiotic combinations are recommended or proposed optionally. We chose vitro and animal studies that provide evidence for the effectiveness of several widely recommended combinations. Results: The combinations serve multiple purposes: they provide empirical coverage while awaiting microbiological results, offer targeted treatment for difficult-to-treat infections, and facilitate oral treatment primarily for staphylococcal infections. The objectives include enhancing bacterial coverage against Gram-positive and Gram-negative bacteria, achieving synergistic effects with bactericidal agents, and reducing the risk of antibiotic resistance. The review outlines specific combinations for fracture-related infections, periprosthetic joint infections, spinal infections, and anterior cruciate ligament reconstruction infections, emphasizing the importance of tailoring antibiotic choices based on local epidemiology and patient history. The review also addresses potential drawbacks of combination therapy, such as toxicity, higher costs, and drug interactions, underscoring the complexity of managing orthopedic infections effectively. Conclusions: According to the guidelines, several different proposals are made, depending in part on the countries’ epidemiology. In a well-defined situation, various authors propose either monotherapy or a combination of antibiotics. When a combination is suggested, the choice of antibiotics is based on the expected effect: broadening the spectrum, enhancing bactericidal activity, achieving a synergistic effect, or reinforcing biofilm activity to optimize the treatment. Full article

Acid mine drainage, a consequence of exposure of sulfide mining waste to weathering processes, results in significant water, sediment, and soil contamination. This contamination results in acidophilic ecosystems, with low pH values and elevated concentrations of sulfate and potentially toxic elements. The São Domingos mine, an abandoned site in the Iberian Pyrite Belt, lacks remediation measures and has numerous waste dumps, which are a major source of contamination to local water systems. Therefore, this study examines sediment accumulation in five mine dams along the São Domingos stream that traverses the entire mine complex. Decades of sediment and waste transport since mine closure have resulted in dam-clogging processes. The geochemical, mineralogical, and magnetic properties of the sediments were analyzed to evaluate the mineralogical controls on the mobilization of potentially toxic elements. The sediments are dominated by iron oxides, oxyhydroxides, and hydroxysulfates, with jarosite playing a key role in binding high concentrations of iron and toxic elements. However, no considerable correlation was found between potentially toxic elements and magnetic parameters, highlighting the complex behavior of these contaminants in acid mine drainage-affected systems. Full article

Background/Objectives: Opioid use disorder (OUD) remains a severe health problem globally, resulting in substantial social and economic challenges. While existing medications for managing OUD are proven to be effective, they also present certain challenges. A vaccine offers a promising therapeutic strategy to combat OUD and potentially reduce the risk of overdose death. The TT-6-AmHap heroin conjugate vaccine has effectively reduced heroin-induced pharmacological effects in behavioral assays as well as demonstrated the induction of high titer and high affinity antibody responses in mice and rats. In this GLP study conducted in rabbits, the potential local and systemic toxicity of the TT-6-AmHap heroin vaccine in combination with or without adjuvants ALF43 and Alhydrogel^® (ALFA) was investigated. Methods: Male and female New Zealand White rabbits were administered with vaccines or a saline control intramuscularly at two-week intervals over a 57-day study period. The presence, persistence or reversibility of any toxic effects of the vaccine was determined over a four-week recovery period. Results: Administration of TT-6-AmHap with or without the adjuvants induced high antibody-specific IgG in treatment groups compared to the controls. The study found no TT-6-AmHap-related effects on mortality, physical examinations, dermal Draize observations, body weights, body weight changes, food consumption, ophthalmology, clinical pathology (hematology, coagulation, clinical chemistry, and urinalysis), macroscopic pathology, or organ weights. Conclusions: Under the conditions of this study, these results demonstrate that the TT-6-AmHap vaccine with or without adjuvants was well tolerated, immunogenic, and the effects were not considered adverse in both male and female rabbits. Full article

Pteridium aquilinum (bracken fern) poses a global threat to biodiversity and to the health of both animals and humans due to its toxic metabolites and aggressive ecological expansion. In northern Spain, particularly in regions of intensive livestock farming, these risks may be exacerbated, calling for urgent assessment and monitoring strategies. In this study, we implemented a multidisciplinary approach to evaluate the toxicological and ecological relevance of P. aquilinum through four key actions: (a) quantification of pterosins A and B in young fronds (croziers) using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS); (b) analysis of in vivo genotoxicity of aqueous extracts using Drosophila melanogaster as a model organism; (c) a large-scale survey of local livestock farmers to assess awareness and perceived impact of bracken; and (d) the development and field application of a drone-based mapping tool to assess the spatial distribution of the species at the regional level. Our results confirm the consistent presence of pterosins A and B in croziers, with concentrations ranging from 0.17 to 2.20 mg/g dry weight for PtrB and 13.39 to 257 µg/g for PtrA. Both metabolite concentrations and genotoxicity levels were found to correlate with latitude and, importantly, with each other. All tested samples exhibited genotoxic activity, with notable differences among them. The farmer survey (n = 212) revealed that only 50% of respondents were aware of the toxic risks posed by bracken, indicating a need for targeted outreach. The drone-assisted mapping approach proved to be a promising tool for identifying bracken-dominated areas and provides a scalable foundation for future ecological monitoring and land management strategies. Altogether, our findings emphasize that P. aquilinum is not merely a local concern but a globally relevant toxic species whose monitoring and control demand coordinated scientific and policy-based efforts. Full article

Approximately 90% of liver cancer cases are classified as hepatocellular carcinomas (HCCs), with chemotherapy and immunotherapy being the most recommended treatment options. While conventional chemotherapy specifically targets rapidly dividing cancer cells, it can also impact on healthy cells that are proliferating quickly. This collateral damage to healthy cells, along with the potential for cancer cells to develop resistance, presents significant challenges for conventional chemotherapy in liver cancer patients. Hepatic artery infusion of chemotherapy (HAIC) generally leads to reduced toxicity and fewer side effects. The process of catheter insertion is usually performed under local anesthesia, with lidocaine being the preferred choice to combine with various chemotherapeutics in HCC treatment. In our study, we explored the effects of repurposing lidocaine in combination with cisplatin or 5-fluorouracil (5-FU) on two HCC cell lines, HepG2 and Hep3B. Our cytotoxicity analysis revealed that lidocaine functions as a chemosensitizer for cisplatin and 5-FU in both HepG2 and Hep3B cells. Specifically, we observed an increase in the subG1 population and a reduction in cytosolic reactive oxygen species in cisplatin- or 5-FU-treated HepG2 and Hep3B cells. Interestingly, lidocaine selectively decreased the reduced/oxidized glutathione ratio in cisplatin- or 5-FU-treated HepG2 cells but not in Hep3B cells. Furthermore, lidocaine induced endoplasmic reticulum stress, apoptosis, mitochondrial membrane depolarization, lipid peroxidation, and autophagy while suppressing cellular proliferation HepG2 and Hep3B cells. In conclusion, our study demonstrates the synergistic potential of combining lidocaine with cisplatin or 5-FU for the treatment of HCC, indicating that lidocaine may serve as an effective chemosensitizer. These findings highlight a new clinical advantage of using repurposing lidocaine as a chemosensitizer in the current HAIC procedure, suggesting that this combination warrants further exploration through rigorous clinical trials. In the future, we can better optimize therapeutic regimens, potentially leading to improved patient outcomes in HCCs. Full article

This study investigates the effect of the surface functionalization of tungsten disulfide (WS₂) nanoparticles with aminoacetic acid (glycine) on the structure, curing behavior, and mechanical performance of epoxy nanocomposites. Aminoacetic acid, as a non-toxic, bio-based modifier, enables a sustainable approach to producing more efficient nanofillers. Functionalization, as confirmed by FTIR, EDS, and XRD analyses, led to elevated surface polarity and greater chemical affinity between WS₂ and the epoxy matrix, thereby promoting uniform nanoparticle dispersion. The strengthened interfacial bonding resulted in a notable decrease in the curing onset temperature—from 51 °C (for pristine WS₂) to 43 °C—accompanied by an increase in polymerization enthalpy from 566 J/g to 639 J/g, which reflects more extensive crosslinking. The SEM examination of fracture surfaces revealed tortuous crack paths and localized plastic deformation zones, indicating superior fracture resistance. Mechanical testing showed marked improvements in flexural and tensile strength, modulus, and impact toughness at the optimal WS₂ loading of 0.5 phr and a 7.5 wt% aminoacetic acid concentration. The surface-modified WS₂ nanoparticles, which perform dual functions, not only reinforce interfacial adhesion and structural uniformity but also accelerate the curing process through chemical interaction with epoxy groups. These findings support the development of high-performance, environmentally sustainable epoxy nanocomposites utilizing amino acid-modified 2D nanofillers. Full article

Chloroplasts, as the organelles primarily responsible for photosynthesis, require a substantial supply of iron ions. Conversely, due to Fe toxicity, the homeostasis of these ions is subject to tight regulation. Permease in chloroplast 1 (PIC1) has been identified as the primary iron importer into chloroplasts. However, previous studies suggested the existence of a distinct pathway for Fe transfer to chloroplasts, likely involving mitoferrin-like 1 (MFL1) protein. In this work, Arabidopsis MFL1 (AtMFL1) and its cucumber homolog (CsMFL1) were characterized using, among others, Arabidopsis protoplasts as well as both yeast and Arabidopsis mutants. Localization of both proteins in chloroplasts has been shown to be mediated via an N-terminal transit peptide. At the gene level, MFL1 expression profiles differed between the model plant and the crop plant under varying Fe availability. The expression of other genes involved in chloroplast Fe homeostasis, including iron acquisition, trafficking, and storage, was affected to some extent in both AtMFL1 knockout and overexpressing plants. Moreover, root growth and photosynthetic parameters changed unfavorably in the mutant lines. The obtained results imply that AtMFL1 and CsMFL1, as putative chloroplast iron transporters, play a role in both iron management and the proper functioning of the plant. Full article

This study provides an up-to-date assessment of the environmental status in the area of the S/s Stuttgart wreck in the southern Baltic Sea, focusing on macrozoobenthos, sediment chemistry, and contamination in Mytilus trossulus soft tissues. Comparative analyses from 2016 and 2023 revealed increased species richness and distinct benthic assemblages, shaped primarily by depth and distance from the wreck. Among macrozoobenthos, there dominated opportunistic species, characterized by a high degree of resistance to the unfavorable state of the environment, suggesting adaptation to local conditions. Elevated concentrations of heavy metals were detected in sediments, with maximum values of Cd—0.85 mg·kg⁻¹, Cu—34 mg·kg⁻¹, Zn—119 mg·kg⁻¹, and Ni—32.3 mg·kg⁻¹. However, no significant correlations between sediment contamination and macrozoobenthos composition were found. In Mytilus trossulus, contaminant levels were mostly within regulatory limits; however, mercury concentrations reached 0.069 mg·kg⁻¹ wet weight near the wreck and 0.493 mg·kg⁻¹ at the reference station, both exceeding the threshold defined in national legislation (0.02 mg·kg⁻¹) (Journal of Laws of 2021, item 568). Condition indices for Macoma balthica were lower in the wreck area, suggesting sublethal stress. Ecotoxicological tests showed no acute toxicity in most sediment samples, emphasizing the complexity of pollutant effects. The data presented here not only enrich the existing literature on marine pollution but also contribute to the development of more effective environmental protection strategies for marine ecosystems under international protection. Full article

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9)-mediated genome editing has emerged as a transformative tool in medicine, offering significant potential for cancer therapy because of its capacity to precisely target and alter the genetic modifications associated with the disease. However, a major challenge for its clinical translation is the safe and efficient in vivo delivery of CRISPR/Cas9 components to target cells. Nanotechnology is a promising solution to this problem. Nanocarriers, owing to their tunable physicochemical properties, can encapsulate and protect CRISPR/Cas9 components, enabling targeted delivery and enhanced cellular uptake. This review provides a comprehensive examination of the synergistic potential of CRISPR/Cas9 and nanotechnology in cancer therapy and explores their integrated therapeutic applications in gene editing and immunotherapy. A critical aspect of in vivo CRISPR/Cas9 application is to achieve effective localization at the tumor site while minimizing off-target effects. Nanocarriers can be engineered to overcome biological barriers, thereby augmenting tumor-specific delivery and facilitating intracellular uptake. Furthermore, their design allows for controlled release of the therapeutic payload, ensuring sustained efficacy and reduced systemic toxicity. The optimization of nanocarrier attributes, including size, shape, surface charge, and composition, is crucial for improving the cellular internalization, endosomal escape, and nuclear localization of CRISPR/Cas9. Moreover, surface functionalization with targeting ligands can enhance the specificity of cancer cells, leading to improved gene-editing accuracy. This review thoroughly discusses the challenges associated with in vivo CRISPR/Cas9 delivery and the innovative nanotechnological strategies employed to overcome them, highlighting their combined potential for advancing cancer treatment for clinical application. Full article

Cassava is the sixth most important food crop and is cultivated in more than 100 countries. The crop tolerates low soil fertility and drought, enabling it to play a role in climate adaptation strategies. Cassava generally requires careful preparation to remove toxic hydrogen cyanide (HCN) before its consumption, but HCN concentrations can vary considerably between varieties. Climate change and low inputs, particularly carbon and nutrients, affect agriculture in Pacific Island countries where cassava is commonly grown alongside traditional crops (e.g., taro). Despite increasing popularity in this region, there is limited experimental data about cassava crop management for different local varieties, their relative toxicity and nutritional value for human consumption, and their interaction with changing climate conditions. To help address this knowledge gap, three field experiments were conducted at the Koronivia Research Station of the Fiji Ministry of Agriculture. Two varieties of cassava with contrasting HCN content were planted at three different times coinciding with the start of the wet (September-October) or dry (April) seasons. A time series of measurements was conducted during the full 18-month or differing 6-month durations of each crop, based on destructive harvests and phenological observations. The former included determination of total biomass, HCN potential, carbon isotopes (δ¹³C), and elemental composition. Yield and nutritional value were significantly affected by variety and time of planting, and there were interactions between the two factors. Findings from this work will improve cassava management locally and will provide a valuable dataset for agronomic and biophysical model testing. Full article