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BACKGROUND: Supportive care to ensure optimal quality of life is an essential component of cancer care and symptom control across the lifespan. Ongoing advances in cancer treatment, increasing toxicity from many novel treatment regimes, and variations in access to care and cancer outcomes across the globe and resource settings present significant challenges for supportive care delivery. To date, no overarching framework has been developed to guide supportive care development worldwide. As an initial step of the Multinational Association of Supportive Care in Cancer (MASCC) Supportive Care 2030 Movement, we developed a targeted, unifying set of ambition statements to envision the future of supportive cancer care. METHODS: From September 2022 until June 2023, we used a modified Delphi methodology to develop and attain consensus about ambition statements related to supportive cancer care. Leaders of MASCC Study Groups were invited to participate in an Expert Panel for the first two Delphi rounds (and a preliminary round to suggest potential ambition statements). Patient Advocates then examined and provided input regarding the ambition statements. FINDINGS: Twenty-seven Expert Panelists and 11 Patient Advocates participated. Consensus was attained on 13 ambition statements, with two sub-statements. The ambition statements addressed global standards for guideline development and implementation, coordinated and individualized care, dedicated supportive oncology services, self-management, needs for screening and actions, patient education, behavioral support, financial impact minimization, comprehensive survivorship care, and timely palliative care, reflecting collaboration, coordination and team-based approach across all levels. INTERPRETATION: This study is the first to develop shared ambitions for the future of supportive cancer care on a global level. These ambition statements can facilitate a coordinated, resource-stratified, and person-centered approach and inform research, education, clinical services, and policy efforts. FUNDING: This project received funding support from Prof Raymond Chans NHMRC Investigator Grant (APP1194051).

IntroductionPirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment.MethodsHere we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs).ResultsOf 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy.ConclusionsPirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.

ContextRotenone is a toxic chemical found in various plants, including some used as food. Rotenone poisoning can be fatal and there is no antidote. Mechanistically, rotenone inhibits mitochondrial complex I, leading to reduced ATP production, compensatory glycolytic upregulation and secondary lactate production, and oxidative stress. Our literature review examined acute rotenone poisoning in humans, including exposure scenarios, clinical presentations, and treatments.MethodsWe searched five databases for relevant literature from database inception through the search date: July 12, 2022, pairing controlled vocabulary and keywords for "rotenone" with terms relating to human exposures and outcomes, such as "ingestion," "exposure," and "poisoning." We included all peer-reviewed reports found using the search terms where the full English text was available. Data abstracted included the number, age, weight, and sex of the exposed person(s), country where exposure happened, exposure scenario, ingestion context, estimated dose, clinical features, whether hospitalization occurred, treatments, and outcomes.ResultsAfter removing non-qualifying sources from 2,631 publications, we identified 11 case reports describing 18 victims, 15 of whom were hospitalized and five died. Most cases occurred in private quarters where victims unknowingly consumed rotenone-containing plants. Vomiting and metabolic acidosis occurred most commonly. Some patients exhibited impaired cardiopulmonary function. Supportive treatment addressed symptoms and included gastric lavage and/or activated charcoal to remove rotenone from the stomach, vasopressors for hypotension, mechanical ventilation for respiratory insufficiency, and sodium bicarbonate for acidosis. Some patients received N-acetylcysteine to counter oxidative stress.ConclusionsRotenone poisoning, though rare, can be fatal. Exposure prevention is impractical since rotenone is found in some plants used as food or pesticides. Cases may be under-diagnosed because symptoms are non-specific and under-reported in English-language journals since most cases occurred in non-English speaking countries. Treatments are supportive. Exploring antioxidant therapy in animal models of rotenone poisoning may be indicated considering rotenone's mechanism of toxicity.

Liv-52, an herbal formulation consisting of seven distinct plants and Mandur Bhasma, is recognized for its hepatoprotective, anti-inflammatory, and antioxidant properties. To investigate the pharmacological potential of each phytochemical from these plants, we conducted ADMET analysis, molecular docking, and molecular dynamic simulations to identify potent molecules capable of inhibiting the interaction between Alpha-fetoprotein (AFP) and Cysteine aspartyl protease 3 (Caspase-3/CASP3). In our study, we have used molecular docking of all the compounds against AFP and filtered them on the basis of ADME properties. Among the compounds analyzed, (-) Syringaresinol from Solanum nigrum, exhibited good binding interactions with AFP, the highest binding free energy, and maintained stability throughout the simulation along with favorable drug likeness properties based on ADME and Toxicity analysis. These findings have strongly indicated that (-) Syringaresinol is a potential inhibitor of AFP, providing a promising therapeutic avenue for hepatocellular carcinoma (HCC) treatment by inhibiting the interaction between AFP and CASP3, thereby reinstating normal CASP3 activity. Further in vitro studies are imperative to validate the therapeutic efficacy of (-) Syringaresinol as an AFP inhibitor, potentially impeding the progression of HCC. [ABSTRACT FROM AUTHOR]

Introduction: Research on gaming and gaming habits has predominantly focused on younger populations, particularly males. The main objective of this study was to analyze gender-based differences in gamer profiles, considering variables related to gaming habits and the gaming community. Methods: A total of 180 Spanish university students currently engaged in video gaming (M = 21.51 years, SD = 3.09, 57.4% male) participated in the study by completing an online questionnaire addressing gaming characteristics such as the age of onset, gaming hours, motives of gaming, and perceived toxicity in the video gaming community. Results: The results revealed statistically significant gender differences in the age of gaming initiation, weekly gaming hours, community toxicity, and several gaming motivations, including customization, cognitive challenge, violent gratification, and social interaction. Linear discriminant analysis identified that higher scores in the age of initiation and customization, along with lower scores in violent gratification and community toxicity, formed the combination of predictor variables that most strongly distinguished between genders. Conclusion: Understanding these gender differences is essential for capturing current gaming trends and addressing the needs of diverse gamers. Finally, the potential clinical implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Periodontitis, affecting approximately 3.9 billion individuals globally, significantly impacts quality of life and has raised interest in its potential systemic effects. Sodium perborate, a common component in oral care products for biofilm control, is widely used, though concerns about its safety persist. This study aimed to evaluate the in vitro toxicity of six commercial oral care products and varying concentrations of sodium perborate, utilizing human gingival fibroblasts (HGF) and keratinocytes (HaCat) as cell models. Methods: Experiments were performed in both 2D monolayer and 3D cultures using MTT and electrical impedance assays, adhering to the manufacturer's recommended exposure time of 30–60 s for product testing. For the reconstructed epidermis model, a prolonged exposure time of 42 min was applied, following the Organization for Economic Cooperation and Development (OECD) Test Guideline 439. Results: Results indicated that all products and sodium perborate at 1 mg/mL were cytotoxic in monolayer cultures. However, at concentrations relevant to commercial formulations (0.06 mg/mL sodium perborate), no significant toxicity was observed. In contrast, the 3D culture models, including spheroids and reconstructed epidermis, exhibited minimal to no cytotoxic effects for the commercial products, with sodium perborate showing no significant toxicity below 0.1 mg/mL. The reconstructed epidermis model, used as surrogate for oral mucosa, further confirmed that the products were non-irritating, in compliance with OECD TG 439 standards. Discussion: This study highlights the importance of considering exposure time, dosage, and cellular model when assessing the safety of oral care products. While 2D models are useful for preliminary screenings, 3D models provide a more physiologically relevant assessment, emphasizing the need for robust testing protocols to ensure product safety. [ABSTRACT FROM AUTHOR]

Background: Microplastics, polymer-based particles < 5 mm, affect plant–soil systems positively or negatively, suggesting there are different modes of action. Microplastics, as particles, have physical effects but the leaching of additives likely contributes chemical mechanisms, both of which may be dependent on microplastic size. To disentangle such mechanisms, we established a controlled experiment involving polypropylene and polyethylene films of small, medium and large size, and we evaluated the individual and combined effect of plastic particles and additives (leachates from plastic particles) on soil properties and plant performance of the phytometer Daucus carota and on bare soils. Results: We find that additives better explained variation in soil properties (e.g., 44.6% vs 1.3%). Soil respiration and aggregation were negatively affected for additives, likely due to the presence of toxic substances. Overall, such effects increased as plastic size decreased. By contrast, plastic particles better explained plant biomass responses. The positive effect of particles on aeration which may promote root penetration and nutrient uptake, and microplastics itself as a source of carbon potentially promoting soil microbial activity, help explain the positive effect of particles on plant biomass. Plants mitigated the negative effects of additives on bare soils while enhancing the positive effects of particles. This improvement was likely linked to an increase in root activity and rhizodeposition, as plastic particles improved soil aeration. The combined effect of additives and particles, which mimics the microplastic found in the soil, mitigated their individual negative effects on plant–soil systems. As the negative effect of additives could have been masked by the positive effects of particles, simply reporting net positive effects would capture only part of the response. Conclusions: Additives and plastic particles differently affect soil properties and plant biomass. Additives primarily negatively affect soil properties due to toxic substances, while plastic particles enhance plant biomass likely by improving soil aeration. When examining microplastics effects on terrestrial systems (i.e., the combined effect of additives and particles), the negative effect of additives may be masked by the positive effects of plastic particles. Reporting only net positive effects risks overlooking these underlying negative effects. Plants can mitigate the negative impacts of additives and amplify the positive effects of plastic particles. Our study emphasizes the importance of investigating both the individual and combined effects of additives and particles to fully understand and address the impacts of microplastics on terrestrial ecosystems. [ABSTRACT FROM AUTHOR]

Objectives: Literature data are scarce on concurrent chemoradiotherapy (CCRT) with S-1 for locally advanced nasopharyngeal carcinoma (LANPC) treatment. This study compared the efficacy and safety of the S-1 versus platinum-based CCRT in LANPC treatment. Methods: This study enrolled 547 patients newly diagnosed with LANPC who underwent CCRT with S-1 or platinum at three institutions. Propensity score matching in a 1:1 ratio balancing baseline features was performed. Survival and adverse effects were compared between groups. Results: Of 160 patients in the cohort, 100 eligible were propensity score matched. Matched dataset analyses showed a higher 5-year overall survival rate (87.1% vs. 84.7%, P = 0.833), progression-free survival (79.6% vs. 75.5%, P = 0.669), locoregional recurrence-free survival (87.0% vs. 84.7%, P = 0.518), and distant metastasis-free survival (84.8% vs. 83.0%, P = 0.780) in the S-1 group than in the platinum-based CCRT group, although not statistically significant. Objective response rate (98.0% vs. 88.0%, P = 0.117) was significantly higher in the S-1 than in the platinum-based regimen, although it was not statistically reflected. Compared with platinum-based, those undergoing S-1-based chemotherapy demonstrated a higher incidence of grade 3 mucositis (20.0% vs. 2.0%, P = 0.016) in the S-1 group and a lower incidence of leukopenia (44.0% vs. 68.0%, P = 0.033), neutropenia (28.0% vs. 52.0%, P = 0.032), anemia (22.0% vs. 44.0%, P = 0.040), nephrotoxicity (4.0% vs. 20.0%, P = 0.028), and nausea/vomiting (30.0% vs. 56.0%, P = 0.019). Conclusion: The results suggest that S-1 can be used as a concurrent chemotherapy regimen during radiotherapy for patients with LANPC, since it presents a noninferior survival benefit compared with platinum and shows tolerable adverse effects. [ABSTRACT FROM AUTHOR]

Background: The global demographic shift towards an aging population is generating a rise in neurodegenerative conditions, with Alzheimer's disease (AD) as the most prominent problem. In this landscape, the use of natural supplements has garnered attention for their potential in dementia prevention. Curcumin (Cur), derived from Curcuma longa, has demonstrated promising pharmacological effects against AD by reducing the levels of inflammatory mediators. However, its clinical efficacy is hindered by poor solubility and bioavailability. Our study introduces the use of H-Ferritin nanocages (HFn) as a nanoformulation vehicle for Cur, aiming to enhance its therapeutic potential for AD. In this work, we characterized a nanoformulation of Cur in HFn (HFn-CUR) by evaluating its safety, stability, and its transport across the blood-brain barrier (BBB) in vitro. Moreover, we evaluated the efficacy of HFn-CUR by transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from both AD patients and healthy controls (HC), and by using the well-established 5xFAD mouse model of AD. Results: Our data show that HFn-CUR exhibits improved water dispersibility, is non-toxic, and can traverse the BBB. Regarding its activity on PBMCs from AD patients, HFn-CUR enhances cellular responses to inflammation and reduces RAGE-mediated stress. Studies on an AD mouse model demonstrate that HFn-CUR exhibits mild beneficial effects on cognitive performance. Moreover, it effectively reduces microgliosis and astrogliosis and in vivo in mouse, suggesting potential neuroprotective benefits. Conclusions: Our data suggest that HFn-CUR is safe and effective in reducing inflammation in both in vitro and in vivo models of AD, supporting the need for further experiments to define its optimal use. [ABSTRACT FROM AUTHOR]

Objective Design Setting Animals Interventions Measurements and Main Results Conclusions To quantify and characterize plasma cannabinoid concentrations in cases of suspected cannabis toxicity in dogs, identify potential correlations between clinical signs and plasma concentrations, and assess the specificity of cannabis toxicity diagnosis based on clinical signs alone.Observational study.Veterinary teaching hospital.Thirty‐eight client‐owned animals.Blood was collected from dogs presenting to the emergency room for suspected cannabinoid intoxication based on history or physical examination findings. Samples were analyzed using a validated liquid chromatography–tandem mass spectrometry method for the cannabinoids Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), and their active metabolites.The most common abnormality observed was ataxia (35/38 dogs), with urinary incontinence, lethargy, and hyperesthesia also commonly noted. Cannabinoids were quantifiable in 37 of 38 plasma samples (97.4%), with THC the predominant cannabinoid (range: 1.99–2748 ng/mL). Lower concentrations of CBD (up to 115.3 ng/mL) and cannabinoid metabolites were detected. Of the clinical signs recorded, only abnormal reflexes were statistically correlated with the THC concentration at the time of sampling (P = 0.01).A diagnosis of suspected cannabinoid toxicity based on case history and clinical presentation was confirmed via quantifiable plasma concentrations in nearly all cases. Although the range of plasma cannabinoid concentrations was broad, the clinical signs observed were generally similar. Other than the presence of abnormal reflexes, clinical signs were not associated with plasma THC concentrations. Subsequent confirmation of cannabinoids in plasma indicates that cannabis toxicity in dogs can be diagnosed with high specificity by veterinarians based only on history and clinical abnormalities. [ABSTRACT FROM AUTHOR]

Antibody–drug conjugates (ADCs) have become a vital class of therapeutics in oncology because of their ability to selectively deliver potent drug molecules to tumor cells. However, ADC‐associated toxicities cause high failure rates in the clinic and hinder their full potential. Due to the complex structure and pharmacokinetics of ADCs, it is challenging to identify the drivers of their toxicities. Here, quantitative analysis was performed to correlate the incidence of clinical adverse events (AEs) with nine different commonly measured exposure parameters collected from study‐level summary data. We considered ADC analytes for different classes of ADCs, to identify ADC analytes that are strongly associated with the AEs for ADCs. Published clinical exposure and safety data for any grade and grade ≥3 AEs from 40 publications across six ADCs and three payloads were collected and analyzed. Exposure‐AE relationships were quantified using logit models, and the strength of the correlations and rank order were determined. The analysis suggests that deruxtecan ADC‐related toxicities correlated most strongly with the exposure of the free payload; monomethyl auristatin E (MMAE) ADC‐related toxicities correlated with the free MMAE area under the curve; and pyrrolobenzodiazepine ADC‐related toxicities correlated with no specific analyte but the dose. These findings agree with the published literature and support the notion that AE profiles are often shared by ADCs that deliver the same cytotoxic payload. The exposure–AE relationships presented here, together with identification of the most informative ADC analytes, may facilitate more focused mechanistic studies on the drivers of clinical AEs and could support dosing decisions during clinical development of ADCs. [ABSTRACT FROM AUTHOR]

ABSTRACT Acetaminophen (APAP) is a well‐known drug that, in high doses, induces hepatotoxicity and nephrotoxicity. This study has investigated the preventive effect of the extract and fractions of Ribes khorasanicum on APAP‐induced liver and kidney damage. In this experiment, after analysis of the extract using FTIR, toxicity was induced by APAP on the 7th day. Before that, the extract and their aqueous, ethyl acetate, and n‐hexane fractions were administrated orally. 24 h after APAP administration, the animals were sacrificed. The liver and kidney were removed for the evaluation of oxidation and biochemical markers, including SGOT, SGPT, ALP, LDH, albumin, urea, creatinine, and bilirubin and also for histopathological evaluations. The safety of the extract was evaluated based on the MTT. Also, expression of the NF‐kB is done. Administration of Ribes khorasanicum significantly decreased the biochemical parameters compared to the APAP. Oxidative parameters, as well as histopathological changes in preventive groups, were improved compared to the APAP in both tissues. The results showed that the aqueous and ethyl acetate fractions of the extract had a better effect than the whole extract and n‐hexane fraction against APAP toxicity. [ABSTRACT FROM AUTHOR]

Polygalae radix (PR) is the dried root of Polygala tenuifolia Willd. and Polygala sibirica L. and enjoys the reputation as the "key medicine for nourishing life." In this study, information about " Polygala tenuifolia Willd.," " Polygala sibirica L.," and "Yuanzhi" was retrieved from scientific databases, including Google Scholar, Baidu Scholar, Web of Science, PubMed, CNKI, and Wan Fang Data. Information from Chinese herbal medicine classics, Yaozhi Data, and the Gaide Chemical Network was also collected. Information related to botany, phytochemistry, pharmacology, toxicity, industrial applications, and processing is summarized in this paper to tap its potentialities and promote its further development and clinical application. More than 320 metabolites have been isolated from PR; saponins, xanthones, and oligosaccharide esters are the main functional metabolites. Pharmacological research shows that its pharmacological action mainly focuses on resisting nervous system diseases, and it also has the functions of anti-oxidation, anti-inflammation, anti-tumor, anti-pathogenic microorganisms and others. The gastrointestinal irritation of its saponins impeded its application, but this irritation can be reduced by controlling the dosage, compatibility with other herbs, or processing. The future progress of PR faces opportunities and challenges. More attention should be paid to the traditional application and processing methods of PR recorded in ancient books. The lack of safety and clinical studies has limited its application and transformation of achievements. Moreover, it is one-sided to take the content of only a few metabolites as the index of processing optimization and quality control, which cannot reflect the full pharmacological and toxicological activities of PR. [ABSTRACT FROM AUTHOR]

The leaves of Citrus deliciosa Tenore were collected in southern Brazil, dried, and subjected to the hydrodistillation process to obtain the essential oil. The extraction of essential oil yielded 0.97% ± 0.04. The chromatographic profile of this compound revealed 11 substances, being methyl N-methyl-anthranilate (75.1%), γ-terpinene (13.8%), and Limonene (7%) as major substances. The essential oil shows antifungal action against all tested yeasts, with promising action against Cryptococcus neoformans, Cryptococcus gattii, and Trichosporon asahii. This compound was also able to inhibit the biofilm production of Candida albicans, Candida glabrata, Candida parapsilosis, and T. asahii. The essential oil of tangerine showed weak antioxidant action. It did not show cytotoxicity in human mononuclear cells. It is hoped that these results may guide future studies for the production of formulations that can be used in the treatment of biofilms caused by yeasts, as well as in candidiasis, cryptococcosis, and/or trichosporonosis. [ABSTRACT FROM AUTHOR]

The n-butanol extract of Stachys arvensis (L.) L. aerial parts (BESA) was analysed by LC-HRMS/MS. 43 Polyphenols, including flavonoids, cinnamic acid derivatives, phenylethaoids, chromones, gallotannins, coumarins and chalcones with hyperoside (13.85%), panasenoside (10.31%), myricitrin (7.89%) and sayaendoside (7.16%), as the major compounds, were identified. High total phenolics (470.21 ± 1.22 mg GAE/g extract) and total flavonoids (189.05 ± 0.72 mg QE/g extract) contents were measured. In addition, the BESA exhibited a higher antioxidant effect in CUPRAC (A0.5:0.45 ± 0.03 μg/mL), DPPH (IC50:4.51 ± 0.16 μg/mL) and ABTS (IC50:7.10 ± 0.18 μg/mL) assays than the standards BHA and α-Tocopherol. Moreover the extract showed a good inhibitory effect against BChE (IC50: 145.02 ± 0.03 μg/mL) and α-amylase (IC50:2.66 ± 0.0024 mg/mL). The BESA exhibited an excellent anti-inflammatory activity (IC50:416 ± 0,056 μg/mL) which was close to that of acetylsalicylic acid, used as a control. The BESA was toxic towards T. molitor larvae and it possessed a good antibacterial activity against gram (+) and gram (-) tested strains. [ABSTRACT FROM AUTHOR]

Gonoderma lucidum (G. lucidum) and Cordyceps militaris (C. militaris) are among the many mushrooms known for their long history of use in traditional medicine. Wildcrafted sources of mushrooms including G. lucidum and C. militaris can be limited from a scarcity and quality perspective, but solid fermentation processes in cultivation settings can provide an efficient way to deliver whole mushroom preparations of a consistent composition. Despite the historical use of these mushrooms, few published reports have explored their potential subchronic oral toxicity or genotoxicity, either from specific components or whole mushroom preparations. The purpose of this study was to assess the potential for acute toxicity, subchronic toxicity, and genotoxicity of powders produced from G. lucidum mycelial biomass and fruiting body ("Organic Reishi M2-102-02 powder") cultured on oats, and C. militaris mycelial biomass, stroma, and fruiting body ("Organic Cordyceps M2-116-04 powder") cultured on oats. Results of the testing demonstrate that both Organic Reishi M2-102-02 powder and Organic Cordyceps M2-116-04 powder were not acutely toxic, did not exhibit subchronic oral toxicity in rats at doses up to the highest dose tested of 2,000 mg/kg bw/day, and did not have genotoxic potential based on in vitro and in vivo genotoxicity assays. [ABSTRACT FROM AUTHOR]

Background: Antiseizure medications (ASM) exhibit considerable interindividual variability in terms of efficacy and adverse events. Genetic variation is thought to contribute to these differences in clinical outcomes. Specifically, the response to valproic acid (VPA), a widely used ASM, is influenced by multiple pharmacogenetic factors. However, and in contrast to other ASMs such as phenytoin and carbamazepine, there is a paucity of data on the association between VPA and various gene variants. The aim of this study was hence to evaluate the influence of candidate pharmacogenetic variants on VPA efficacy, toxicity and serum concentrations in a homogeneous cohort of patients newly diagnosed with genetic generalized epilepsies (GGE). Methods: In this prospective cohort study, demographic, clinical and treatment outcomes of GGE patients were retrieved from their medical records. Whole exome sequencing was performed in collaboration with Epi25. Gene variants associated with VPA efficacy, metabolism and toxicities were retrieved from PharmGKB. An analysis was then conducted to explore potential associations between these gene variants and VPA clinical outcomes. Results: Of the 166 patients included, 60 (36.1%) experienced treatment failure while 106 (63.9%) achieved treatment success. After adjusting for VPA maintenance dose, carriers of the rs3892097 (CYP2D6) variant were 2.5 times more likely to experience treatment failure compared to wildtype (p = 0.026). The rs1057910 variant (CYP2C9*3) was associated with increased serum VPA concentrations (p = 0.034). Moreover, the rs1137101 variant (LEPR gene , a metabolism regulator) was significantly associated with a higher risk of weight gain (regression coefficient of 3.430 [0.674; 6.186], p = 0.015) and a higher frequency of hair loss (OR = 3.394 [1.157; 9.956], p = 0.026), while the rs4480 variant (SOD2 gene, encoding for a mitochondrial scavenging enzyme) was correlated with a lower frequency of hair loss (OR = 0.276 [0.089; 0.858], p = 0.026). Conclusion: These findings highlight the role of genetic factors in VPA treatment and underscore the potential for developing therapeutic strategies to enhance patient outcomes and minimize adverse effects. [ABSTRACT FROM AUTHOR]

Blighia sapida oil, a substance with a rich history of use for its nutritional, therapeutic, traditional, and cosmetic benefits, was the focus of our study. We investigated the impact of consuming edible oil from B. sapida arils on Wistar rats. The crude oil from unripe arils was extracted using cold pressing and then administered to the rats. The toxicity was evaluated according to the OECD method. Notably, there were no signs of food poisoning or adverse effects on the weight and behavior of the rats treated with B. sapida oils. The LD50 of the oil was more significant than 5000 mg/kg of body weight, and hematological and biochemical parameters did not differ significantly from the control group. Rats fed with an oil‐supplemented diet showed an increase in weight compared to the negative control group. No fatty deposits were found in vital organs, and consuming the oil did not affect the immune system or biochemical biomarkers. However, excessive intake of fat may have harmful effects on tissues. Our findings strongly suggest that B. sapida oil is safe for consumption within reasonable limits. The data we present here reveal that the oil derived from B. sapida is suitable for moderate consumption and may offer various health advantages, a potential that warrants further exploration. [ABSTRACT FROM AUTHOR]

Introduction:Urtica simensis has been used to treat various diseases such as malaria, hypertension, diabetes, gonorrhea, gastritis, body swelling, and wound infections. However, the safety of consuming U. simensis leaves during pregnancy has not been evaluated yet. Therefore, this experimental study was conducted to evaluate the toxic effects of U. simensis leaf extract on the prenatal development of embryos and fetuses in pregnant rats. Methods: Fifty pregnant Wistar albino rats were randomly assigned to five groups of 10 gravid rats for each experiment. Groups I–III were given 70% ethanol leaf extract of U. simensis at doses of 250, 500, and 1000 mg/kg daily from 6th to 12th days of gestation. Groups IV–V were kept as pair‐fed and ad libitum controls. The developing embryos and fetuses were retrieved on 12 days and 20 days of gestation, respectively. Embryos were evaluated for growth and developmental delays. Fetuses were also assessed for growth retardation and external and visceral anomalies. Results: In the embryonic experiment, somite numbers (p = 0.001) and morphological scores (p = 0.029) were significantly decreased in pregnant rats given 1000 mg/kg of U. simensis leaf extract. Embryonic developments of the caudal neural tube (CNT) (p = 0.001), otic system (p = 0.025), olfactory system (p = 0.013), and limb buds (p = 0.026) were significantly delayed in pregnant rats given 1000 mg/kg of extract. Oral administration of 500 mg/kg of U. simensis leaf extract also caused significant developmental delays in the CNT (p = 0.021) and olfactory system (p = 0.032). In the fetal experiment, fetal resorption (p = 0.015) was significantly increased whereas crown rump length (p = 0.012) and fetal weight (p = 0.019) were significantly decreased in pregnant rats given 1000 mg/kg of U. simensis leaf extract. Conclusions: The embryotoxic effects of U. simensis leaf extract were evidenced by significant developmental delays. The fetal toxic effects of U. simensis leaf extract were also shown by significant decreases in fetal growth indices. Therefore, pregnant women should be well informed of the possible toxic effects of consuming U. simensis leaf during pregnancy. [ABSTRACT FROM AUTHOR]

The development of an environmentally benign method for the synthesis of nanoparticles has been facilitated by green chemistry. "Green synthesis" uses a range of biological elements like microbes, plants, and other biodegradable materials to produce NPs. Active biomolecules that are secreted by natural strains and present in the plant extracts serve as both reducing and capping/stabilizing agents. Microorganisms' intracellular enzymes can reduce metal ions, which explains how NPs might potentially nucleate. Plant-based synthesis of nanomaterials is particularly promising owing to abundant resources, simplicity of synthesis, and low cost. Silver nanoparticles (AgNPs) are attracting great attention in the research community due to their wide variety of applications in chemistry, food technology, microbiology, and biomedicine. Recent years have seen a large amount of research on the bio-genic synthesis of AgNPs employing biomaterials like plant extract and bacteria as reducing agents. Herein we discuss a thorough overview of the plant-based synthesis of silver nanoparticles (AgNPs), characterization approaches, applications, and toxicity. The review covers the green chemistry and nanotechnology elements of producing AgNPs, including a thorough discussion of the plant extract mediated synthesis, detailed formation mechanism, and a well-balanced emphasis on hazards and advantages. Based on current developments, the optimisation strategies, applications, and interdisciplinary characteristics are also covered in detail. • Plant-based synthesis of nanomaterials is particularly promising. • A comprehensive review on plant-based AgNPs synthesis. • Synthesis, characterization approaches, applications and toxicity are discussed. [ABSTRACT FROM AUTHOR]

During drug discovery, it is crucial to exclude compounds with toxic effects. The human ether-à-go-go-related gene (hERG) channel is essential for maintaining cardiac repolarization and is a critical target in drug safety evaluation due to its role in drug-induced arrhythmias. Inhibition of the hERG channel can lead to severe cardiac issues, including Torsades de Pointes tachycardia. Understanding hERG inhibition mechanisms is essential to avoid these toxicities. Several structural studies have elucidated the interactions between inhibitors and hERG. However, orientation and resolution issues have so far limited detailed insights. Here, we used digitonin to analyze the apo state of hERG, which resolved orientation issues and improved the resolution. We determined the structure of hERG bound to astemizole, showing a clear map in the pore pathway. Using this strategy, we also analyzed the binding modes of E-4031 and pimozide. These insights into inhibitor interactions with hERG may aid safer drug design and enhance cardiac safety. [Display omitted] • Binding modes of hERG inhibitors were revealed with higher resolution cryo-EM data • Preferred particle orientation issues of cryo-EM data were resolved by using digitonin • The binding modes of hERG to astemizole, E-4031, and pimozide were determined • This study provides insights into hERG-inhibitor interactions for safer drug design Miyashita et al. overcame preferred orientation issue and they obtained improved cryo-EM data, which enabled them to elucidate the binding mechanisms of the hERG inhibitors astemizole, E-4031, and pimozide. These structural data are of interest to guide safer drug design and avoid drug-induced arrhythmias. [ABSTRACT FROM AUTHOR]

Background: The other side of radiotherapy (RT), in addition to the cytotoxic effect, is the ability to modulate the immune system in terms of activation or suppression, also depending on the dose and fractionation delivered. This immune RT effect can be detected both locally in the irradiated tumor site and in the peripheral blood. The aim of this study was to assess the consequence of pelvic irradiation on peripheral immune cells and cytokine secretions in localized prostate cancer (PC) patients undergoing pelvic irradiation with a simultaneous moderately hypofractionated prostate/prostate bed boost by Volumetric Modulated Arc Therapy (VMAT). Furthermore, we analyzed whether there was a correlation between these peripheral immune parameters and acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. Methods: Thirty-eight PC patients were treated with pelvis irradiation (dose per fraction 1.8 Gy) and simultaneous hypofractionated (median dose per fraction: 2.7 Gy) prostate/prostate bed boost. A longitudinal analysis was performed for 12 months on peripheral blood to assess changes in 9 different lymphocyte subpopulations by flow cytometry and 10 circulating cytokines by Multiplex Luminex assay and ELISA. Results: Our analysis revealed that basal IFN-γ serum values were significantly lower in the definitive (curative intent for patients with prostate) patient group respect to the post-operative one. All the lymphocyte subsets and IFN-α, IFN-β and Il-2 peripheral concentrations displayed significant variations between the different time points considered. The immune cell population that suffers the greatest RT toxicity in the blood was B lymphocyte. We found an interesting correlation between basal TGF-β1 and late GU toxicity. In particular, TGF-β1 concentrations before RT were significantly higher in patients that experienced grade 2-3 of late GU toxicity, respect to grade 0-1. Exploring possible correlations between some clinical/biological findings and radiation planning parameters, we found no statistical significance. Conclusions: Our study analyzed, in the context of hypofractionated radiotherapy in prostate cancer, different parameters of the peripheral immune system. We have highlighted longitudinally the peripheral behavior of the different lymphocyte subpopulations and of a group of 10 cytokines during the first year after RT. One of the analyzed cytokines, such as TGF-β1, has proven to be promising predictive factor of severe late GU toxicity. [ABSTRACT FROM AUTHOR]

This review provides an overview on the fate and behavior of imidacloprid, a neonicotinoid insecticide, in agricultural environments. The study focuses on four key aspects: adsorption and leaching of imidacloprid in soil, degradation and hydrolysis of imidacloprid in soil and water, uptake and persistence of imidacloprid in plants, and volatilization of imidacloprid to the atmosphere. The review presents the latest findings from research on each of these topics. While imidacloprid is highly effective at controlling pests, it is also known to persist in the environment, posing risks to non-target organisms such as bees, birds, and aquatic life. Moreover, there is increasing concern about its potential to accumulate in the soil and water systems, which may have long-term effects on the ecosystem. The review suggests that better understanding of the behavior and fate of imidacloprid in agricultural environments is essential for developing effective strategies to minimize its environmental impact. [ABSTRACT FROM AUTHOR]

Background and aims: A number of case reports have documented the occurrence of acute hepatic and renal toxicity during treatment with deferasirox (DFX). The precise mechanisms underlying these adverse events remain unclear, with the time to toxicity varying considerably between patients—some experiencing it within weeks of treatment initiation, while others after several years. Recent studies have underscored the association of pharmacogenetic variants in genes responsible for the metabolism and clearance of DFX (ABCC2 , ABCG2 , and UGT1A1) in the development of toxicity. We present the case of an 8-year-old patient with beta thalassemia major who developed acute hepatic failure years after the initiation of DFX therapy. After ruling out the most likely causes, we performed a pharmacogenetic analysis, which suggested a possible link between the patient's genotype and the development of toxicity. Methods: Sanger sequencing was performed for the most extensively studied single nucleotide polymorphisms (SNPs) studied associated with changes in transporter/enzyme function: ABCC2 rs717620 (c.-24C>T), rs2273697 (c.1249G>A), rs8187710 (c.4544G>A), rs369192412 (g.99781071delG); ABCG2 rs2231142 (c.421C>A); UGT1A1 *6 rs4148323 (c.211G>A), *28 rs3064744 (g.233760235TA[8]), *36 rs3064744 (g.233760235TA[6]) and *37 rs3064744 (g.233760235TA[9]). Results: The patient is heterozygous for two ABCC2 variants, namely rs717620 (c.-24C>T) and rs2273697 (c.1249G>A). These variants have the potential to cause a reduction in transporter function, which could in turn result in decreased drug clearance and increased toxicity. Discussion: The precise mechanism by which toxicity developed in this case remains unclear and is likely multifactorial. However, it is probable that the presence of SNPs in the gene ABCC2 played a substantial role. Our findings align with those of previously published reports of remarkably similar cases, where patients also exhibited genetic variants in the gene ABCC2. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to systematically analyze the efficacy and toxicity of lurbinectedin as a second-line or subsequent treatment for extensive-stage small cell lung cancer (ES-SCLC). Methods: Candidate studies were identified in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases up to 1 May 2024. Objective remission rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted, respectively. The efficacy and toxicity of lurbinectedin in ES-SCLC were analyzed by meta-analysis. Results: Six eligible prospective studies were included in this meta-analysis, including 536 patients with ES-SCLC who received second-line or subsequent treatment. In pooled analysis, the ORR of lurbinectedin was 35% (95% confidence interval [CI] 29–41), DCR was 67% (95%CI 58–76), DOR was 5.33 months (95%CI 4.51-6.16), PFS was 3.38 months (95%CI 2.59-4.17), and OS was 7.49 months (95%CI 5.11–9.87). The incidence of AEs and severe adverse events (SAEs) was 92% (95%CI 78–100) and 37% (95%CI 19–57), respectively. The most common AEs were leukopenia, neutropenia, anemia, and thrombocytopenia, with incidences of 81% (68–91), 74% (57–88), 73% (35–98) and 57% (46–68), respectively. Conclusion: As a promising alternative for second-line treatment for ES-SCLC, lurbinectedin has a certain level of efficacy and a favorable safety profile. The integration of lurbinectedin with other therapeutic modalities presents an emerging area warranting further investigation. [ABSTRACT FROM AUTHOR]

Mosquito-borne diseases continue to pose significant threats to human populations, especially in developing and underdeveloped regions, where access to effective preventive measures remains limited. Mosquito repellents represent a cornerstone in the arsenal against these diseases, providing a barrier against mosquito bites. Mosquito repellents come in various formulations, including topical ointments and commercial vaporizers, with varying compositions. Common constituents include deodorized kerosene (DOK) as a solvent, pyrethroids, amides, essential oils for fragrance, and synergists. Despite their widespread use, the toxicological profiles of these repellents remain inadequately understood, raising questions about their safety in prolonged or excessive exposure scenarios. However, while their efficacy in preventing mosquito-borne illnesses is well-established, concerns persist regarding their potential toxicity to humans and the environment. This review critically examines the existing literature on the toxicity of mosquito repellents, focusing on their adverse effects on human health and environmental sustainability. Through an extensive analysis of available research, this review aims to shed light on the potential health risks associated with mosquito repellents, such as dermatological irritation, respiratory complications, and allergic reactions in humans. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) cause 30% of deaths each year, and in 2030, around 23.6 million people will die due to CVDs. The major challenge is to obtain molecules with minimal adverse reactions that can prevent and dissolve blood clots. In this context, fibrinolytic enzymes from diverse microorganism sources have been extensively investigated due to their potential to act directly and specifically on the fibrin clot, preventing side effects and performing potential thrombolytic effects. However, most researches focus on the purification and characterization of proteases, with little emphasis on the mechanism of action and pharmacological characteristics, including toxicity assays which are essential to assess safety and side effects. Therefore, this work aims to emphasize the importance of evaluations indicating the toxicological profile of fibrinolytic proteases through in vitro and in vivo tests. Both types of assays contribute as preclinical stage in drug development and are crucial for clinical applications. This scarcity creates arbitrary barriers to further studies. This work should further encourage the development of studies to ensure the safety and effectivity of fibrinolytic proteases. HIGHLIGHTS: Suggested pre-clinical trials aim to validate more specific methods for fibrinolytic enzymes; Current toxicity standards can be adapted to better assess the profile of fibrinolytic enzymes; The class of fibrinolytic enzymes must be carefully evaluated according to the method of application. [ABSTRACT FROM AUTHOR]

Chromium (Cr) toxicity, even at low concentrations, poses a significant health threat to various environmental species. Cr is found in the environment in two oxidation states that differ in their bioavailability and toxicity. While Cr(III) is essential for glucose metabolism, the oxyanion chromate Cr(VI) is mostly of anthropogenic origin, toxic, and carcinogenic. The sources of Cr in the environment are multiple, including geochemical processes, disposal of industrial waste, and industrial wastewater. Cr pollution may consequently impact the health of numerous plant and animal species. Despite that, the number of published studies on Cr toxicity across environmental species remained mainly unchanged over the past two decades. The presence of Cr in the environment affects several plant physiological processes, including germination or photosynthesis, and consequently impacts growth, and lowers agricultural production and quality. Recent research has also reported the toxic effects of Cr in different aquatic and terrestrial organisms. Whereas some species showed sensitivity, others exhibited tolerance. Hence, this review discusses the understanding of the ecotoxicological effect of Cr on different plant and animal groups and serves as a concise source of consolidated information and a valuable reference for researchers and policymakers in an understanding of Cr toxicity. Future directions should focus on expanding research efforts to understand the mechanisms underlying species-specific responses to Cr pollution. [ABSTRACT FROM AUTHOR]

Alkaloids are naturally occurring compounds with complex structures found in natural plants. To further improve the understanding of plant alkaloids, this review focuses on the classification, toxicity and mechanisms of action, providing insight into the occurrence of alkaloid-poisoning events and guiding the safe use of alkaloids in food, supplements and clinical applications. Based on their chemical structure, alkaloids can be divided into organic amines, diterpenoids, pyridines, isoquinolines, indoles, pyrrolidines, steroids, imidazoles and purines. The mechanisms of toxicity of alkaloids, including neurotoxicity, hepatoxicity, nephrotoxicity, cardiotoxicity and cytotoxicity, have also been reviewed. Some cases of alkaloid poisoning have been introduced when used as food or clinically, including accidental food poisoning, excessive consumption, and poisoning caused by the improper use of alkaloids in a clinical setting, and the importance of safety evaluation was illustrated. This review summarizes the toxicity and mechanism of action of alkaloids and provides evidence for the need for the safe use of alkaloids in food, supplements and clinical applications. [ABSTRACT FROM AUTHOR]

In this study, the toxic and teratogenic effects of three commercial drugs and their active ingredients on Xenopus laevis embryos before and after ozonation were evaluated using the Frog Embryos Teratogenesis Assay–Xenopus (FETAX). First, the median lethal concentration (LC50) and, if data were available, the median effective concentration, teratogenic index and minimum growth inhibitory concentration were determined for each drug substance without ozonation. Then, the active substance amounts of three selected nominal concentrations (LC50/2, LC50, and LC50×2) of each test substance before ozonation were measured by HPLC analysis and the toxicity of these substances was evaluated after 2, 3, 4, and 5 h of ozonation. In addition, degradation products that may occur during ozonation were evaluated by LC-MS analysis. The 96-h LC50s of Dolphin–diflunisal, Dichloron–diclofenac sodium, and Apranax–naproxen drug–active substance pairs were determined to be 22.3 and 11.1, 25.7 and 18.7, and 47.8 mg active substance/L and 45.3 mg/L, respectively. According to the FETAX test results, the Dolphin–diflunisal drug–active ingredient pair did not cause growth retardation in exposed embryos. Dichloron–diclofenac sodium and Apranax–naproxen drug–active ingredient pairs were both teratogenic and growth inhibitory. In the second stage of the study, in which the effectiveness of ozonation in eliminating the toxic effects of drugs is evaluated, it is seen that ozonation is partially successful in eliminating the toxic effects of Dolphin–diflunisal and Dichloron–diclofenac sodium pairs, but insufficient for eliminating the effects of the Apranax–naproxen pair. [ABSTRACT FROM AUTHOR]

Streptozotocin (STZ) is used as a diabetes-inducing agent in experimental animal studies. However, it is known that STZ-induced diabetic animals show significant increases in oxidative stress parameters and neurodegeneration besides their blood glucose level. In this study, the acute and subacute toxic effects of STZ on the liver, sciatic nerve, and brain tissues were investigated in vivo rat model. Sprague-Dawley rats were divided into two groups; while 50 mg/kg STZ was administered ip to the STZ group, only saline was administered to the control group. After STZ administration, three units (100 U/mL) of subcutaneous insulin glargine were applied daily to prevent the formation of diabetes. At 24 h, 1,2, and 4 weeks after applications, rats from each group were sacrificed and tissues were removed under anesthesia. At the end of the study, compared to the control, a significant decrease in SOD and GST activity and an increase in lipid peroxidation were detected in the liver and sciatic tissues of rats in the STZ-treated group in the first 24h. Considering the TUNEL, NFκB, and NOS2 expressions, it was noted that while the effects of STZ on the liver were observed in the acute stage (24h), it had subacute effects on the brain. When apoptosis-related gene expression (Bcl-2, Bax, CASP3, CASP8, CASP9, TNF-α) and immunohistochemistry were evaluated, the apoptotic effect of STZ was observed mostly in sciatic nerve tissues. Within the scope of the study, it was revealed that STZ did not only show selective toxicity to pancreatic β cells but also very toxic to other tissues and organs. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the genotoxic effect of Propineb fungicide at different concentrations (0.167, 0.335 and 0.670 mg L−1) and different treatment times (24, 48, 72 and 96 h) on Danio rerio. At the end of the treatment periods, blood was collected from the fish with a heparin injector; smear preparations were prepared, fixed and stained. In the prepared preparations, the numbers of cells with MN and erythrocyte nucleus abnormalities were examined. It was found that propineb increased micronucleus formation at all treatment times and concentrations and induced the formation of erythrocytes with morphological abnormal nuclei such as segmented, kidney-shaped, notched, vacuolated nuclei and binucleated. The increase in micronucleus formation and the number of erythrocytes with abnormal nuclei were found to be concentration and treatment time-dependent. In conclusion, in this study, Danio rerio erythrocytes were used to evaluate the genotoxic effects of propineb fungicide on aquatic organisms, which have an important place in environmental risk assessment criteria. Since fungicides used in agricultural control such as propineb may have the potential to be genotoxic to aquatic organisms, the results of toxicity tests should be taken into consideration in the selection and use of concentrations of these chemicals. [ABSTRACT FROM AUTHOR]

Summary: The Glasgow prognostic score (GPS) and CAR‐HEMATOTOX (CAR‐HT) score identify multiple myeloma (MM) patients at high risk for immune‐mediated toxicity and early mortality with cellular immunotherapy. However, their association with outcomes in patients receiving T‐cell redirecting bispecific antibodies (bsAb) is unclear. This multi‐centre retrospective study examines the association of baseline GPS and CAR‐HT scores with outcomes in 126 MM patients treated with bsAb. Overall, 19% were identified as GPS high risk but did not experience increased toxicity or mortality. Conversely, high‐risk CAR‐HT patients had a higher incidence of infections and inferior survival, suggesting a need for aggressive infection mitigation strategies. [ABSTRACT FROM AUTHOR]

Emodin (EMO) is an anthraquinone compound derived from Rheum palmatum L., which has rich pharmacological activity. However, studies have shown that EMO may cause hepatotoxicity. In this study, EMO was combined with tetrandrine and prepared as lipid nanoparticles (E-T/LNPs). The anti-liver fibrosis activity of EMO before and after formulation was evaluated by zebrafish and mice. In addition, the toxicity of EMO and E-T/LNPs was compared and the toxicity–efficacy concentrations of E-T/LNPs in zebrafish were verified. E-T/LNPs are morphologically stable (particle size within 100 nm), have high encapsulation efficiency and good stability, and are capable of long-lasting slow release in vitro. The combination and preparation can reduce the toxicity and enhance the effect of EMO, and increase the toxicity and effect concentration of E-T/LNPs in vivo. In a short period, low doses of E-T/LNPs can be used for the treatment of liver fibrosis; high doses of E-T/LNPs cause toxicity in vivo. Immunohistochemistry showed that E-T/LNPs inhibited hepatic fibrosis by downregulating the levels of IL-1β and TGF-β. Based on the advantages of combination therapy and nanotechnology, it can play a role in reducing the toxicity and increasing the efficacy of EMO in the treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

When exposed to X-rays, scintillators emit visible luminescence. X-ray-mediated optogenetics employs scintillators for remotely activating light-sensitive proteins in biological tissue through X-ray irradiation. This approach offers advantages over traditional optogenetics, allowing for deeper tissue penetration and wireless control. Here, we assessed the short-term safety and efficacy of candidate scintillator materials for neuronal control. Our analyses revealed that lead-free halide scintillators, such as Cs3Cu2I5, exhibited significant cytotoxicity within 24 h and induced neuroinflammatory effects when injected into the mouse brain. In contrast, cerium-doped gadolinium aluminum gallium garnet (Ce:GAGG) nanoparticles showed no detectable cytotoxicity within the same period, and injection into the mouse brain did not lead to observable neuroinflammation over four weeks. Electrophysiological recordings in the cerebral cortex of awake mice showed that X-ray-induced radioluminescence from Ce:GAGG nanoparticles reliably activated 45% of the neuronal population surrounding the implanted particles, a significantly higher activation rate than europium-doped GAGG (Eu:GAGG) microparticles, which activated only 10% of neurons. Furthermore, we established the cell-type specificity of this technique by using Ce:GAGG nanoparticles to selectively stimulate midbrain dopamine neurons. This technique was applied to freely behaving mice, allowing for wireless modulation of place preference behavior mediated by midbrain dopamine neurons. These findings highlight the unique suitability of Ce:GAGG nanoparticles for X-ray-mediated optogenetics. The deep tissue penetration, short-term safety, wireless neuronal control, and cell-type specificity of this system offer exciting possibilities for diverse neuroscience applications and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Plant-derived carbon dots (P-CDs) are gaining attention in environmental remediation due to their cost-effectiveness, availability, and lower toxicity compared with chemically synthesized carbon dots. This review comprehensively examines the recent advancements in the synthesis and application of P-CDs, with a particular emphasis on their efficacy in the sensing of heavy metals, which are among the most pervasive environmental contaminants. A detailed comparative analysis is presented by evaluating the performance of P-CDs against their chemically synthesized counterparts based on key parameters, such as optimal operating conditions and detection limits. Furthermore, sensing the potential of P-CDs towards every heavy metal ion has been discussed with in-depth mechanistic insights. Additionally, this review explores the industrial applications and future directions of P-CDs. This review provides a comprehensive analysis of -P-CDs for heavy metal sensing, aiming to enhance their sensitivity and selectivity toward heavy metal ions. [ABSTRACT FROM AUTHOR]

The escalating release of multi-walled carbon nanotubes (MWCNTs) into the environment has raised concerns due to their potential ecotoxicological impacts. However, their combined phytotoxicity with heavy metals such as copper (Cu) is still unclear. This study investigated the individual and combined toxic effects of MWCNTs (MWCNT, MWCNT-OH, and MWCNT-COOH) and Cu2+ on ryegrass (Lolium multiflorum), uniquely considering different addition orders. The results show that Cu severely inhibited the growth of ryegrass while MWCNTs exhibited a hormesis effect on ryegrass. When MWCNT and Cu were combined, the malondialdehyde (MDA) content in ryegrass showed a 32.39% increase at 20 mg/L MWCNT exposure, suggesting reduced oxidative stress. However, at the higher concentration of 1000 mg/L, it led to a significant 75.22% reduction in ryegrass biomass. MWCNT-COOH had the most pronounced effect, reducing the total chlorophyll content by 39.76% compared to unmodified MWCNT and by 10.67% compared to MWCNT-OH (500 mg/L). Additionally, pre-induced MWCNTs might alleviate the Cu in the plant by 23.08–35.38% through adsorption in the nutrient solution. Small molecule organic acids and amino acids primarily mediated the response to environmental stress in ryegrass. This research provides crucial insights into understanding the complex interactions of MWCNT and Cu2+ and their combined effects on plant ecosystems. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous irAEs are some of the most reported adverse reactions to ICIs. This prospective monocentric study seeks to offer a comprehensive overview of the skin toxicity associated with these therapies in a single-center institution, with the aim of describing their incidence and our approach for management. Additionally, we aim to highlight the importance of dermatological assessment for affected patients, as it can have a major impact on both their quality of life and the decision to continue treatment. Background/Objectives: The landscape of advanced melanoma treatments has shifted dramatically in recent years. Target therapy and immunotherapy have changed the management of patients with both metastatic (stage IV according to AJCC 8th ed.) and nodal (stage IIB/C and III) disease. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, high-grade or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining a patient's quality of life is of paramount importance. Methods: We undertook a prospective, monocentric, and descriptive study in Bologna, Italy, including patients referred to the Oncologic Dermatology Unit of IRCCS AOU of Bologna who developed biopsy-proven cutaneous adverse events (AE) under treatment with immunotherapy for cutaneous melanoma with nodal (stage IIB/C, III) and metastatic (stage IV) disease from January 2016 to April 2024. Results: In 202 identified patients, 75 (37.5%) developed skin AEs. Ipilimumab was causal for 48.1% of skin AEs, followed by nivolumab (37%) and pembrolizumab (31.4%). Recorded types of skin AEs included erythematous rash, vitiligo, alopecia, lichenoid, maculopapular, acneiform, urticarial, psoriasiform, granulomatous, eczematous, and severe cutaneous AEs, such as Erythema multiforme/Stevens-Johnson syndrome and bullous autoimmune dermatoses. Most AEs were low-grade [CTCAE 1–2] (97%) and typically occurred after 10 weeks of treatment. Conclusions: This study comprehensively describes skin AEs occurring during systemic treatment with ICIs for cutaneous melanoma at a single center. [ABSTRACT FROM AUTHOR]

The cotton bollworm, Helicoverpa armigera (Hübner), is one of the important insect pests of cotton throughout the world. Considering the adverse effects of chemical pesticides, it is necessary to find eco-friendly substitute agents for managing insect pests, including H. armigera. Plant-derived insecticides have been introduced as suitable candidates to replace detrimental synthetic chemicals. In this study, the toxicities of water, ethanol, and n-hexane extracts of eucalyptus and thyme, as well as their wettable powder formulations, against H. armigera larvae were investigated. The treated larvae represented different degrees of abnormalities, such as larva-pupa intermediate and pupa-adult stages in their different ages until they turned into pupae and completed the breeding cycle. The results showed that the considered formulations of extract of n-hexane and ethanol, and concentrations had significant effects on the mortality rates of the larvae (P≤0.05) but the interaction of extracts and concentrations was not significant. The mortality rates were enhanced by increasing the tested concentrations. The LC50 values (lethal concentrations to kill 50% of the tested insects) were 343.758% (water), 10.171% and 23.264% (ethanol), and 0.404% and 0.490% (n-hexane) for the eucalyptus and thyme extracts within 24 hours, respectively, indicating higher toxicities of n-hexane extracts. The LC50 values of wettable powder formulations of the thyme and eucalyptus extracts were 120.68% and 177.75% (water) and 36.17% and 74.65% (ethanol), respectively, which represented the greater toxicities of these types of formulations. Therefore, the wettable powder formulations of ethanol and water extracts of thyme were more toxic than their solution formulations. Based on the results of this study, wettable powder formulation of eucalyptus and thyme extracts had promising potential for H. armigera management. [ABSTRACT FROM AUTHOR]

As the single largest class of specialty chemicals, surfactants are consumed in huge quantities in our daily life and in many industrial areas. In the past, the attention was focused entirely on technical performance. However, starting from the 1970s and 80s, surfactant related environmental concerns have become the main driving force to upgrade surfactant production technology to make more benign or "greener" products. For this reason, environmental issues, dermatological effects, and oral toxicity are the main priorities when surfactants are considered for a specific purpose. In this paper, we present five cases to demonstrate how the surfactant industry tackles these challenges to mitigate the environmental and health effects associated with surfactant consumption. We also discuss the important role played by surfactants in a current carbon capture and storage (CCS) strategy to reduce the CO2 level in the atmosphere. Surfactant-based stable CO2 foam flooding is a well-established enhanced oil recovery technique. It has been considered to be an economically realistic procedure to sequester large amounts of CO2 in geological formations. [ABSTRACT FROM AUTHOR]

• Methanolic leaf extract of chinaberry killed 85 % H. indicola workers after 6 days. • MetOH and water extracts showed dose and time-dependent trends on non-durable wood. • GC–MS: chinaberry leaf extracts contain antifeedants like phytol and terpenoids. Hetertermes indicola Wasman (Blattodea: Rhinotermitidae) is a highly wood-destructive termite species in the urban settings of Pakistan. This study evaluated the biocidal action of Melia azedarach leaf extract in different solvents on H. indicola by conducting choice and no-choice feeding deterrence assays using impregnated palatable wood under field and laboratory conditions. Dose-dependent and time-dependent trends were observed in the leaf extracts of M. azedarach at different concentrations (500, 1000, and 1500 ppm) using solvent water and methanol with 80–100 % termite mortality after 6 days of exposure. A key outcome was the higher termiticidal efficacy of methanolic extract compared to aqueous extract under both field and laboratory conditions. The LC50 values of 358 ppm for methanol and 466 ppm for aqueous extract after 15 days in a laboratory no-choice experiment exhibit a quantitative measure of chinaberry leaf extract toxicity. A significant reduction in mean percent weight loss (8.26 %) of treated wood with 1500 ppm of M. azedarach leaf extract in methanol was observed under field conditions. In conclusion, triterpenoids and phytol present in methanolic leaf extract demonstrated higher efficacy in both lab and field conditions making a solid foundation for the further development of natural wood preservatives. Since they induced rapid lethargic conditions in termites and digestive toxicity which leads to minimum loss of treated wood. [ABSTRACT FROM AUTHOR]

• Iron oxide nanoparticles decreased the microbial activity in soil. • Nanoparticle addition caused significant shift in soil bacterial community. • Beneficial bacterial community showed decreased abundance after nanoparticle amendments. • Changes in bacterial abundance affected the plant growth and yield attributes. Although nanotechnology has the potential to revolutionize the current agriculture system, there have been a few reported studies of the impact of nanoparticles on plants, showing that nanoparticles could have adverse effects. Studies have shown that these materials can have significant adverse effects on both plants and soil microbes in agroecosystems. In this study, we evaluated the effect of Fe 2 O 3 −NPs on the soil microbial community in connection to the growth of soybean plants. Nanoparticles were added to the soil at three different concentrations (0.4 %, 0.8 %, and 1.2 %). The effect of these soil amendments on soil bacterial community and plant growth attributes was checked. Results showed that the lowest concentration of the nanoparticles (0.4 %) did not affect the soil bacterial community structure and size, while nanoparticle amendment at 0.8 % and 1.2 % significantly altered the bacterial community size and structure. Taxonomic analysis revealed that the addition of nanoparticles suppressed the abundance of beneficial microbes that play essential plant-friendly roles. Moreover, plant growth and yield was significantly affected by adding nanoparticles at 0.8 % and 1.2 % nanoparticle concentration in the soil, which was correlated with the corresponding suppression of bacterial genera in the respective groups. These results reveal the potential toxicity of Fe 2 O 3 −NPs to soil microbe, which in turn affects plant growth and suggests that the hazardous impacts of the nanoparticles should be investigated before their large-scale application. [ABSTRACT FROM AUTHOR]

Environ 10 à 15 % des patientes atteintes d'un cancer du sein seront atteintes d'une récidive locale après un traitement conservateur initial ou une mastectomie. La mastectomie totale est historiquement le traitement de référence en cas de récidive locale. Cependant, la réirradiation peut être une option en cas de second traitement conservateur en association à une segmentectomie ou en cas de récidive sur la paroi thoracique afin d'améliorer le taux de contrôle local. Différentes modalités sont disponibles : la curiethérapie, la radiothérapie externe avec ou sans hyperthermie. Bien que les résultats carcinologiques soient encourageants, cette situation complexe nécessite une sélection rigoureuse des patientes et une maîtrise technique afin d'obtenir le meilleur taux de contrôle local et de limiter la toxicité. Cet article présente une revue des données de la littérature sur les indications et différentes techniques de réirradiation des récidives homolatérales des carcinomes mammaires afin d'apporter une aide à la prise de décision en pratique clinique. Approximately 10 to 15% of patients with breast cancer will have a local recurrence after initial conservative treatment or mastectomy. Total mastectomy has historically been the standard treatment for local recurrence. However, the question of reirradiation may arise as part of a second conservative treatment in conjunction with segmentectomy or in the case of chest wall recurrence to improve local control. Different modalities are available: brachytherapy, external beam radiotherapy with or without hyperthermia. Although the carcinologic results are encouraging, this complex situation requires rigorous patient selection and technical requirements to achieve the best local control and limit toxicity events. This article presents a review of the literature on the different indications and techniques for reirradiation of ipsilateral recurrent breast cancer, with the aim of providing decision support in clinical practice. [ABSTRACT FROM AUTHOR]

Approximately one-third of Americans use healthcare approaches including herbs and botanicals, such as St. John's wort (SJW), to improve overall well-being, gain control over their health, and manage the adverse reactions of conventional therapies. This article examines the use of SJW in cancer care, discussing its pharmacokinetics, toxicity, and potential interactions with cancer treatments while emphasizing the importance of patient education and collaboration between oncology nurses and pharmacists to ensure safe and effective care. [ABSTRACT FROM AUTHOR]

Municipal wastewater may contain toxic substances that have a negative impact on biological treatment processes and receiving waters. This paper presents the wastewater toxicity test results from the Lodz hybrid sewage system. Wastewater is discharged to surface waters through a treatment plant, but also during wet weather, partially without treatment by combined sewer overflows. The research was carried out using the ToxTrakTM method with the use of the microbial community of activated sludge from the wastewater treatment plant in Lodz. The median toxicity, expressed as the degree of inhibition, ranged from 16.0% to 30.7%, but sometimes exceeded 50%. Higher toxicity was observed in wet weather than in dry weather. Seasonal variability was found but typical daily variability was not observed. In the case of sewage samples with the degree of inhibition above 40%, a significant correlation was found with chromium concentration and non-ionic surfactants (Pearson's coefficient correlation above 0.7). [ABSTRACT FROM AUTHOR]

Lead white (basic lead carbonate), before its effective ban in much of Europe from 1989 onwards, was among the most versatile and widespread but also one of the most harmful pigments available. This paper is a critical discussion of the regulation of lead white paint and its consequences from the point of view of conservation and artistic practice in Europe. It looks at who benefited from exemptions to bans, and whether there was resistance to them. Buildings and artworks are both taken into account. The paper discusses nuances in regulation in four European countries which have notable differences in approach (France, Austria, Germany, and the United Kingdom). The centralised regulatory framework of the United Kingdom allows data analysis on the authorised use of the paint since its restriction up to the present day. This dataset shows a steady decrease in the use of the paint by conservators across disciplines. The paper concludes by considering the professional and ethical implications of lead white paint for artists and conservators, in the context of varied regulation and a decline in use. [ABSTRACT FROM AUTHOR]