Reduction Of Toxicity Research Articles

Understanding the Role of Low-Dose Polystyrene Microplastic in Copper Toxicity to Rice Seed (Oryza sativa L.).

There is still much to learn with respect to the potential for microplastics (MPs) to interact with environmental toxins and biota. In the present study, we investigated the effect of MPs on the toxicity of copper (Cu) to rice seeds (Oryza sativa L.). The 7-day median effective concentration (EC50) value of MPs on rice seed germination was 864 mg/L (95% confidence interval [CI] 839 to 897 mg/L). We found that MPs slightly reduced Cu toxicity to rice seeds. The 7-day EC50 of Cu on rice seed germination increased from 7.29 mg/L (95% CI 7.10-7.52 mg/L) to 7.93 mg/L (95% CI 7.58-8.08 mg/L) in the presence of 20 mg/L MPs. We examined this toxicity reduction phenomenon by investigating the role of MPs in the process of Cu transport, Cu accumulation, and metabolic responses. Further investigation found that the MPs used in the present study hardly adsorbed Cu, but these MPs accumulated on the coats of rice seeds and significantly reduced Cu accumulation in rice seedlings. When Cu concentration was 10 mg/L, the presence of MPs reduced the accumulation of Cu in rice seedlings by 34%. We also found that, compared with only Cu present, the addition of MPs resulted in lower reactive oxygen species accumulation and higher catalase activity and glutathione levels in rice seedlings, which also contributed to Cu toxicity reduction. Collectively, the present study shows that polystyrene MPs have the potential to form associations with plant structures which can ultimately impact heavy metal bioaccessibility and therefore toxicity. Environ Toxicol Chem 2024;43:1870-1879. © 2024 SETAC.

Decolourisation and toxicity reduction of azo dye Bismarck Brown by newly isolated Pseudomonas aeruginosa, JKAK strain

ABSTRACT The decolourisation of Bismarck Brown dye by the newly isolated bacterial strain, Pseudomonas aeruginosa (JKAK), was studied at various parameters. Additionally, decolourisation of Bismarck Brown was studied using previously isolated strains; Bacillus sp. (AK1), Lysinibacillus sp. (AK2) and Kerstersia sp. (VKY1). The studies were carried out at temperature (35–50°C), dye concentration (200–800 mg/L), pH (5.5–10.5), metal ions (200–1000 mg/L) and NaCl (5–30 g/L). The optimum pH and temperature were 8.5 and 40°C, respectively. The strains decolourised over 53.75% of 800 mg/L Bismarck Brown after 24 h of incubation. The JKAK strain showed significant halotolerance and decolourised over 90% of the dye in the presence of 30 g/L NaCl. Further, JKAK decolourised over 86.4% of the dye in the presence of 1000 mg/L of Pb2+ and Zn2+ ions. The products of decolourisation were identified as aromatic amines and showed decreased phytotoxicity when compared to the untreated dye.

A phase 2, single arm, European multi-center trial evaluating the efficacy of afatinib as first line or later line treatment in advanced chordoma.

11517 Background: EGFR and Her2 overexpression in chordoma is well known, and chordoma cell-lines and mouse models were proven to be sensitive to EGFR inhibitor afatinib. This phase 2, single arm, European multi-center trial was designed to evaluate the efficacy of afatinib as first- or later-line tyrosine kinase inhibitor (TKI) treatment in advanced chordoma. Here we report efficacy and safety data. Methods: Eligible patients (pts) had locally advanced or metastatic, pathologically proven, EGFR expressing chordoma, not amenable for local therapies, with confirmed measurable and progressive lesions according to RECIST1.1. Pts were treated with afatinib 40mg/day in a 4 week cycle until disease progression (PD), unacceptable toxicity or withdrawal. Radiological tumor response assessment was performed every 3 cycles. The primary endpoint was response defined as progression free survival (PFS) rate ≥12 months (mos) for first-line cohort 1 and ≥ 9 mos for further-line treatment cohort 2, and change from baseline in EORTC QLQ- C30 and Brief pain inventory (BPI) questionnaires. Pts were enrolled using a Simon’s two-stage design, enrolling 13 patients in stage one, ≥3 patients with a PFS ≥ 12 or 9 mos were needed to enter stage two, where 43 pts total were to be enrolled, and ≥13 free from progression at 9 or 12 mos were required to meet the primary endpoint for success. Results: From Jun 2018 to Oct 2022, 47 pts were included. Four were ineligible for efficacy analysis (1 withdrawal, 3 stopped due to toxicity before first radiological evaluation). 34 entered cohort 1, 13 cohort 2. 31 (66.0%) were men, median age was 53 (range 28-85) years. 16 (34.0%) pts received prior systemic therapy (3 chemotherapy, 13 TKI, 2 immunotherapy, 2 other). The PFS rate at 12 mos was 40.0% in cohort 1 (12/30 pts), and 38.5% in cohort 2 (5/13 pts). Overall median PFS was 8.6 mos (95% CI 5.6-13.6); 9.1 mos (95% CI 5.8-16.6) in cohort 1 and 7.1 mos (95% CI 2.8-16.5) in cohort 2. Two pts remained on treatment at time of analysis. Best objective response by RECIST 1.1 was partial response in 4 pts (9.3%), stable disease in 33 (76.7%), PD in 5 pts (11.6%) and 1 (2.3%) unknown due to clinical progression. Median follow-up time was 23.7 mos (interquartile range 11.0-21.2). 16/47 pts (30.4%) experienced grade ≥3 adverse events (AEs). No grade 5 AEs related to afatinib were reported. Most common grade 3-4 afatinib-related AEs were skin toxicity (10.6% of pts), diarrhea (10.6%), mucositis (6.4%), hypertension (4.3%). Dose reduction was needed in 20/47 (42.6%) pts, and at least one dose interruption was needed in 31/47 (66.0%) pts. Conclusions: With a PFS rate at 12 mos of 40.0% in the first-line cohort and 38.5% at 9 mos in the further-line cohort, this phase 2 study met the PFS endpoint. QoLQ data will be provided at the conference . Partial response by RECIST was seen in 4/43 pts. Toxicity and dose reductions were relevant but manageable in most pts. Clinical trial information: NCT03083678 .

Intra-treatment hypoxia directed major radiation de-escalation as definitive treatment for human papillomavirus-related oropharyngeal cancer.

6007 Background: We previously reported that surgery to the primary site with hypoxia-directed de-escalated radiation to the neck for human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) can lead to excellent oncologic outcomes. We now report the results of a successor multi-center phase II trial of hypoxia-directed de-escalated chemoradiotherapy without surgery for HPV+OPC. Methods: HPV+ OPC (T0-2/N1-N2c/AJCC 7th) patients were eligible for enrollment. Tumors without evidence of hypoxia on 18F-FMISO (fluoromisonidazole) PET received de-escalated chemoradiation to 30Gy while those with hypoxia received chemoradiation to 70Gy. The primary objective was achieving a 2-year locoregional control (LRC) of 95% (failure was locoregional recurrence where surgical salvage was unfeasible) with a 7% non-inferiority margin. We enrolled a total of 158 subjects upfront to account for a 5% loss due to death (of reasons other than cancer) or follow-up. Secondary objectives were local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), toxicities, and patient-reported MD Anderson Dysphagia Inventory (MDADI) scores. LF, RF, and DM were estimated using the Cumulative Incidence Function, and OS was estimated using the Kaplan-Meier method. Results were reported up to 1/31/2024. Results: From 4/28/20-4/17/23, 158 HPV+ OPC patients were enrolled where150 patients were eligible for analyses. Patient characteristics: Tonsil (43%); Base of Tongue (47%); unknown primary (10%); >/=10 pack years (22%); T0 (9%), T1 (44%), T2 (47%); N1 (14%), N2a (11%), N2b (59%), N2c (16%). 111 (74%) received 30Gy; 95% cisplatin. With 24 months (8-43) of median follow-up, the 2-year LF, RF, DM rates were 4.2%, 6.9%, 2.0%, respectively. The 2-year overall survival probability was 99%. Only 2 patients could not undergo salvage surgery [one 30Gy (second recurrence); one 70Gy (M1)], both received systemic therapy with durable response. Acute grade 3-4 toxicities were 32% (67% neutropenia). Mean MDADI scores: 92.93 (baseline); 68.24 (3 weeks), 91.45 (4 months) after chemoradiation. Conclusions: These early data indicate that major de-escalation to 30Gy based on hypoxia status achieved significant toxicity reduction without compromise in survival for HPV+ OPC treated with chemoradiation without surgery. Clinical trial information: NCT03323463 .

Australian rheumatologists' perception of autologous haemopoietic stem cell transplantation for the treatment of systemic sclerosis: a cross-sectional survey.

Autologous haemopoietic stem cell transplantation (AHSCT) is an effective treatment for systemic sclerosis (SSc); however, treatment-related toxicity remains a key issue. To investigate the perceptions of rheumatologists on the use of AHSCT for SSc. Australian rheumatologists were asked for their opinion on the role of AHSCT, the indications for treatment and the barriers to the use of AHSCT for SSc. A secondary analysis assessed what factors influenced the perception of AHSCT. A total of 77.8% rheumatologists agreed or strongly agreed with the statement that AHSCT is an accepted treatment for SSc. While 65.1% agreed or strongly agreed that treatment-associated mortality was a significant barrier to referral for AHSCT, only 15.2% agreed or strongly agreed that this risk was unacceptable. Progressive lung or skin disease, or lack of response to other therapies, were considered the main referral criteria. A total of 92.0% of respondents agreed or strongly agreed that reduction of treatment toxicity would increase their likelihood to refer patients for AHSCT. Rheumatologists who were aware of the correct evidence base were more likely to consider AHSCT an acceptable treatment for SSc (4.21 ± 0.7 vs 3.64 ± 0.9, P = 0.007). Rheumatologists desire improved patient selection criteria and access to treatment. In this national survey of rheumatologists, AHSCT is considered an accepted therapy. However, concern about toxicity remains a potential barrier to patient referral. Access, studies to refine patient selection and development of AHSCT protocols that improve safety were identified as key areas of need.

Integrating local and distant radiation-induced lung injury: Development and validation of a predictive model for ventilation loss.

Investigations on radiation-induced lung injury (RILI) have predominantly focused on local effects, primarily those associated with radiation damage to lung parenchyma. However, recent studies from our group and others have revealed that radiation-induced damage to branching serial structures such as airways and vessels may also have a substantial impact on post-radiotherapy (RT) lung function. Furthermore, recent results from multiple functional lung avoidance RT trials, although promising, have demonstrated only modest toxicity reduction, likely because they were primarily focused on dose avoidance to lung parenchyma. These observations emphasize the critical need for predictive dose-response models that effectively incorporate both local and distant RILI effects. We develop and validate a predictive model for ventilation loss after lung RT. This model, referred to as P+A, integrates local (parenchyma [P]) and distant (central and peripheral airways [A]) radiation-induced damage, modeling partial (narrowing) and complete (collapse) obstruction of airways. In an IRB-approved prospective study, pre-RT breath-hold CTs (BHCTs) and pre- and one-year post-RT 4DCTs were acquired from lung cancer patients treated with definitive RT. Up to 13 generations of airways were automatically segmented on the BHCTs using a research virtual bronchoscopy software. Ventilation maps derived from the 4DCT scans were utilized to quantify pre- and post-RT ventilation, serving, respectively, as input data and reference standard (RS) in model validation. To predict ventilation loss solely due to parenchymal damage (referred to as P model), we used a normal tissue complication probability (NTCP) model. Our model used this NTCP-based estimate and predicted additional loss due radiation-induced partial or complete occlusion of individual airways, applying fluid dynamics principles and a refined version of our previously developed airway radiosensitivity model. Predictions of post-RT ventilation were estimated in the sublobar volumes (SLVs) connected to the terminal airways. To validate the model, we conducted a k-fold cross-validation. Model parameters were optimized as the values that provided the lowest root mean square error (RMSE) between predicted post-RT ventilation and the RS for all SLVs in the training data. The performance of the P+A and the P models was evaluated by comparing their respective post-RT ventilation values with the RS predictions. Additional evaluation using various receiver operating characteristic (ROC) metrics was also performed. We extracted a dataset of 560 SLVs from four enrolled patients. Our results demonstrated that the P+A model consistently outperformed the P model, exhibiting RMSEs that were nearly half as low across all patients (13±3 percentile for the P+A model vs. 24±3 percentile for the P model on average). Notably, the P+A model aligned closely with the RS in ventilation loss distributions per lobe, particularly in regions exposed to doses ≥13.5Gy. The ROC analysis further supported the superior performance of the P+A model compared to the P model in sensitivity (0.98vs. 0.07), accuracy (0.87vs. 0.25), and balanced predictions. These early findings indicate that airway damage is a crucial factor in RILI that should be included in dose-response modeling to enhance predictions of post-RT lung function.

An in-depth review of thalidomide's basic moieties

Thalidomide, also referred to as N-phthalimido glutarimide, was initially made available as a sedative by Chemie Grunelthal GmbH in West Germany in 1957. Thalidomide's chemical structure primarily consists of two rings: the phthalimide ring and the glutarimide ring. Although small substitutions in one or both rings might be tolerated without a reduction in toxicity, both of these groups were necessary for embryopathic action. A cyclic chemical structure that is a component of thalidomide is the phthalimide ring. The phthalimide ring is thought to contribute to both the teratogenic (causes birth defects) and some therapeutic aspects of the medication. Another cyclic structure seen in the chemical makeup of thalidomide is the Glutarimide Ring. The pharmacological characteristics of thalidomide are also connected to this portion of the molecule. Based on their activities and structural connections, this review study gives an overview of the interaction between phalidimide and the glutarimide ring for teratogenicity of the thalidomide type. Understanding how thalidomide interacts with the human body, both for its intended therapeutic effects and its negative side effects, especially when taken during pregnancy, is important given the combination of these rings in the drug's chemical structure.

Enhancing in-situ tetracycline degradation in urine environment using boron-modified sewage sludge biochar: Mechanism of carbonate radical promotion

In this work, we reveal the influencing factors and mechanisms of tetracycline removal by peroxydisulfate activated with boron-modified sewage sludge biochar in urine. Advanced characterization techniques showed that the introduced BCO2 and BC2O were the main activation sites for peroxydisulfate, which maintained a high removal rate of tetracycline in synthetic and actual urine (86.48% and 77.35%). HCO3−/CO32− and some organic matter in the urine contributed to the degradation of the tetracycline. Theoretical calculations showed that CO32− in urine could be efficiently adsorbed by the introduced B atoms and converted to CO3·− by peroxydisulfate to assist the degradation of tetracycline, which was attributed to the special electronic structure of the B atoms as well as the strong electron-enrichment ability of the neighboring O atoms. The potential toxicity of tetracycline and its degradation intermediates was further explored, revealing a significant reduction in toxicity during boron-modified sewage sludge biochar/ peroxydisulfate treatment.

Helium Ion Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma.

Helium ion therapy (HRT) is a promising modality for the treatment of pediatric tumors and those located close to critical structures due to the favorable biophysical properties of helium ions. This in silico study aimed to explore the potential benefits of HRT in advanced juvenile nasopharyngeal angiofibroma (JNA) compared to proton therapy (PRT). We assessed 11 consecutive patients previously treated with PRT for JNA in a definitive or postoperative setting with a relative biological effectiveness (RBE) weighted dose of 45 Gy (RBE) in 25 fractions at the Heidelberg Ion-Beam Therapy Center. HRT plans were designed retrospectively for dosimetric comparisons and risk assessments of radiation-induced complications. HRT led to enhanced target coverage in all patients, along with sparing of critical organs at risk, including a reduction in the brain integral dose by approximately 27%. In terms of estimated risks of radiation-induced complications, HRT led to a reduction in ocular toxicity, cataract development, xerostomia, tinnitus, alopecia and delayed recall. Similarly, HRT led to reduced estimated risks of radiation-induced secondary neoplasms, with a mean excess absolute risk reduction of approximately 30% for secondary CNS malignancies. HRT is a promising modality for advanced JNA, with the potential for enhanced sparing of healthy tissue and thus reduced radiation-induced acute and long-term complications.

Tri-phase flame retardant system towards advanced energy-saving building materials with highly efficient fire and smoke toxicity reductions

The extensive usage of rigid polyurethane foam (RPUF) as an energy-saving building materials in construction has raised concerns about fire risks and toxic hazards. To address these challenges, a melamine-derived polyol (MADP) was synthesized using the Mannich reaction, resulting in inherently flame-retardant RPUF materials with the introduction of flame-retardant functional groups. Furthermore, a novel MoS2-Cu2O nanohybrid was prepared and employed to enhance flame retardancy and suppress smoke toxicity in RPUF through a cooperative effect with expandable graphite (EG). The resulting M-RPUF/EG/MoS2-Cu2O nanocomposite exhibited remarkable fire safety, as evidenced by significant reductions in peak heat release rate (PHRR), total heat release (THR), total smoke production (TSP), and peak carbon monoxide (CO) release, amounting to 76.9 %, 64 %, 82 %, and 99 % respectively, compared to pristine RPUF. Furthermore, the nanocomposite effectively addressed interfacial defects and significantly enhanced the mechanical property and thermal stability. The significant improvement in fire safety is mainly ascribed to the catalytic charring effect of MADP and EG, as well as the catalytic oxidation of MoS2-Cu2O nanohybrids, resulting in the formation of a thermally stable protective layer in the condensed phase. Based on these results, the integration of the tri-phase flame retardant system holds great potential for advancing the development of fire-safe polyurethane materials.

Impact of aging and ergothioneine pre-treatment on naphthalene toxicity in lung

Aging increases susceptibility to lung disease, but the topic is understudied, especially in relation to environmental exposures with the bulk of rodent studies using young adults. This study aims to define the pulmonary toxicity of naphthalene (NA) and the impacts of a dietary antioxidant, ergothioneine (ET), in the liver and lungs of middle-aged mice. NA causes a well-characterized pattern of conducting airway epithelial injury in the lung in young adult mice, but NA’s toxicity has not been characterized in middle-aged mice, aged 1–1.5 years. ET is a dietary antioxidant that is synthesized by bacteria and fungi. The ET transporter (ETT), SLC22A4, is upregulated in tissues that experience high levels of oxidative stress. In this study, middle-aged male and female C57BL/6 J mice, maintained on an ET-free synthetic diet from conception, were gavaged with 70 mg/kg of ET for five consecutive days. On day 8, the mice were exposed to a single intraperitoneal NA dose of 50, 100, 150, or 200 mg/kg. At 24 hours post NA injection samples were collected and analyzed for ET concentration and reduced (GSH) and oxidized glutathione (GSSG) concentrations. Histopathology, morphometry, and gene expression were examined. Histopathology of mice exposed to 100 mg/kg of NA suggests reduction in toxicity in the terminal airways of both male (p ≤ 0.001) and female (p ≤ 0.05) middle-aged mice by the ET pretreatment. Our findings in this study are the first to document the toxicity of NA in middle-aged mice and show some efficacy of ET in reducing NA toxicity.

How quickly does FLASH need to be delivered? A theoretical study of radiolytic oxygen depletion kinetics in tissues

Purpose. Radiation delivered over ultra-short timescales (‘FLASH’ radiotherapy) leads to a reduction in normal tissue toxicities for a range of tissues in the preclinical setting. Experiments have shown this reduction occurs for total delivery times less than a ‘critical’ time that varies by two orders of magnitude between brain (∼0.3 s) and skin (⪆10 s), and three orders of magnitude across different bowel experiments, from ∼0.01 to ⪆(1–10) s. Understanding the factors responsible for this broad variation may be important for translation of FLASH into the clinic and understanding the mechanisms behind FLASH. Methods. Assuming radiolytic oxygen depletion (ROD) to be the primary driver of FLASH effects, oxygen diffusion, consumption, and ROD were evaluated numerically for simulated tissues with pseudorandom vasculatures for a range of radiation delivery times, capillary densities, and oxygen consumption rates (OCR’s). The resulting time-dependent oxygen partial pressure distribution histograms were used to estimate cell survival in these tissues using the linear quadratic model, modified to incorporate oxygen-enhancement ratio effects. Results. Independent of the capillary density, there was a substantial increase in predicted cell survival when the total delivery time was less than the capillary oxygen tension (mmHg) divided by the OCR (expressed in units of mmHg/s), setting the critical delivery time for FLASH in simulated tissues. Using literature OCR values for different normal tissues, the predicted range of critical delivery times agreed well with experimental values for skin and brain and, modifying our model to allow for fluctuating perfusion, bowel. Conclusions. The broad three-orders-of-magnitude variation in critical irradiation delivery times observed in in vivo preclinical experiments can be accounted for by the ROD hypothesis and differences in the OCR amongst simulated normal tissues. Characterization of these may help guide future experiments and open the door to optimized tissue-specific clinical protocols.

Graphene Oxide, a Prominent Nanocarrier to Reduce the Toxicity of Alzheimer's Proteins: A Revolution in Treatment.

Graphene oxide, a derivative of graphene, has recently emerged as a promising nanomaterial in the biomedical field due to its unique properties. Its potential as a nanocarrier in the treatment of Alzheimer's disease represents a significant advancement. This abstract outlines a study focused on utilizing graphene oxide to reduce the toxicity of Alzheimer's proteins, marking a revolutionary approach in treatment strategies. The pathological features of Alzheimer's disease, primarily focusing on the accumulation and toxicity of amyloid-beta proteins, have been described in this review. These proteins are known to form plaques in the brain, leading to neuronal damage and the progression of Alzheimer's disease. The current therapeutic strategies and their limitations are briefly reviewed, highlighting the need for innovative approaches. Graphene oxide, with its high surface area, biocompatibility, and ability to cross the blood-brain barrier, is introduced as a novel nanocarrier. The methodology involves functionalizing graphene oxide sheets with specific ligands that target amyloid-beta proteins. This functionalization facilitates the binding and removal of these toxic proteins from the brain, potentially alleviating the symptoms of Alzheimer's disease. Preliminary findings indicate a significant reduction in amyloid-beta toxicity in neuronal cell cultures treated with graphene oxide nanocarriers. The study also explores the biocompatibility and safety profile of graphene oxide in biological systems, ensuring its suitability for clinical applications. It calls for further research and clinical trials to fully understand and harness the benefits of this nanotechnology, paving the way for a new era in neurodegenerative disease therapy.

Lignin and Pluronic-based nanomicelles as promising amiodarone nanocarriers: Synthesis, physical characterization, biological, and in silico evaluations

Lignin, a major component of herbaceous plants, is one of the most abundant natural poly-mers that has lipophilic character and antipathogenic properties. Another biocompatible polymer is Pluronic F127, that can cross the blood brain barrier (BBB). Herein, novel drug delivery nanosystems based on oil-in-water microemulsions made of these two biocompatible polymers were developed to load amiodarone (AM), a cationic amphipathic drug used for treating cardiac arrhythmia that displays antifungal and antibacterial properties. The use of drug delivery nanocarriers enhances the solubilization and controlled release of this medication, thus reducing its therapeutic dosage and associated side effects. The morphology, size and surface charge of the nanomiceles was characterized via scanning and transmission electron microscopy (SEM and TEM), dynamic light scattering (DLS) and zeta potential measurements, respectively, which demonstrated their spherical shape, with an average diameter of 27 nm and a zeta potential of −25 mV. Very high entrapment efficiencies were attained for both types of nanomicelles (79.1% and 83.1% for lignin and F127, respectively). Furthermore, both types of AM-loaded nanomicelles exhibited a slower release profile compared to the free drug. Cytotoxicity assay with morphological examination of NIH/3T3 fibroblast cells confirmed a reduction in drug toxicity upon loading onto the nanocarriers. Blood cultures in a chocolate agar medium corroborated that the antibacterial properties of AM are preserved after nanomicelle encapsulation. The interactions of AM with F127 and lignin monomers were investigated via quantum mechanical computations, which revealed the formation of strong hydrogen bonds, the most intense being between AM and lignin. Overall, these novel formulations exhibit great potential for the sustained and targeted AM delivery.

Unraveling the intrinsic activity origin of sludge-derived biochar for boosted chlorination of diclofenac: Key role of persistent free radicals

Economical and eco-friendly chlorine-based advanced oxidation processes (AOPs) have been urgently demanded to enhance the green abatement of emerging micropollutants. Herein, sludge-derived biochar (SBC) was innovatively introduced to activate free available chlorine (FAC) to enhance the elimination of diclofenac (DCF) among pH 5.0–11.0. Pyrolysis of municipal sludge endowed biochar with superior structure, various chemical compositions, and electronic properties, among which carbon-centered persistent free radicals (PFRs) were verified as the dominant active sites for enhanced chlorination based on correlation analysis. Electron spin resonance and electrochemical tests firstly verified that PFRs could mediate electron transfer toward FAC and dissolved oxygen to generate multiple reactive species of •OH, ClO•, 1O2, and O2•−. Further investigation revealed that enhanced DCF chlorination relied on both radical attack by •OH, ClO•, O2•− and direct electron transfer. Meanwhile, the regeneration of PFRs mediated by FAC and electron-rich DCF greatly promoted the reusability of SBC800. SBC800/FAC system was much superior to sole chlorination in terms of toxicity reduction and anti-interference capacity. This study innovatively introduced SBC as a green and sustainable catalyst to enhance chlorination efficiency, and provided new insights into the activation potential and mechanism of PFRs for chlorination.

Gastrointestinal Incomplete Degradation Exacerbates Neurotoxic Effects of PLA Microplastics via Oligomer Nanoplastics Formation.

Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28-day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease-like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU-i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health.

A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety

The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control of the COVID-19 pandemic. However, mRNA vaccines have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, and pericarditis. In this study, we investigated the potential of trehalose glycolipids-containing LNP (LNP S050L) to reduce the risks associated with ionizable lipids. Trehalose glycolipids can form hydrogen bonds with polar biomolecules, allowing the formation of a stable LNP structure by replacing half of the ionizable lipids. The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity, respectively. Furthermore, mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity, including in the heart, spleen, and liver, while sustaining gene expression and immune efficiency, compared to conventional LNPs (Con-LNPs). Our findings suggest that LNP S050L, a trehalose glycolipid-based LNP, could facilitate the development of safe mRNA vaccines with improved clinical safety.

In vitro reduction of toxicity of heavy metals and oxidation by using wheat gluten subunit hydrolysates

Gluten subunit hydrolysates were produced from kiwifruit extract, and their radical scavenging activity and ability to bind three potentially toxic elements (Pb, Hg, Cd) were assessed. Based on electrophoresis analysis, the molecular weight of all hydrolysates was <10 kDa. The DPPH· (72.98 ± 2.04 µm mol TE/g) and ABTS· (285.81 ± 2.5 µm mol TE/g) scavenging activities of glutenin hydrolysates were significantly (p ≤ 0.05) higher than those of other subunit hydrolysates. The soft wheat gliadin hydrolysate was chelated with heavy metals (WGLYHHM). At a neutral pH, its binding capacity with Pb+2 (99 %) was significantly (p < 0.05) higher than that of Hg+2 (87 %) and Cd+ (43 %) at pH 3. The differences in binding sites and apparent structures of WGLYH before and after chelation with heavy metals were also verified by SEM, XRD, and FT-IR. These findings confirmed the efficiency of gluten-subunit hydrolysates in scavenging radical activity and heavy metal content, which could have potential health benefits.

Efficient bimetallic activation of sulfite by CoFe-LDH for bisphenol A removal: Critical role of Co/Fe ratio on ROS generation

The sulfite (S(IV))-based advanced oxidation process is an emerging approach for the treatment of phenolic pollution. In this study, CoFe-layered double hydroxides (CoFe-LDHs), showing superior physicochemical properties as catalysts, were applied to activate S(IV) for bisphenol A (BPA) degradation. The results show that the Co/Fe molar ratios play a crucial role in regulating the physicochemical properties, degradation capacity, and activation mechanism of the catalysts, with Co3Fe1-LDH exhibiting the best performance in BPA degradation. The degradation of BPA is significantly influenced by pH and dissolved oxygen, and proceeds through bimetallic synergism and both radical and non-radical pathways. However, with increasing Co/Fe ratio, SO4•− gradually assumes a more prominent role in degradation by the system, and the contributions from high-valent metals and HO• gradually diminish. Additionally, the system brought about a substantial reduction in toxicity after degradation, and the catalyst demonstrated promise in consecutive recycling experiments, the degradation of other organics, and tests in actual water bodies.

Liquid-phase microextraction approach using supramolecular solvent formed in aqueous systems based on di(2-ethylhexyl)phosphoric acid salt: Spectrophotometric determination of antipyrine in saliva

In this study, di(2-ethylhexyl)phosphoric acid salt was investigated as a double-chain anionic surfactant for supramolecular solvent formation in a liquid-phase microextraction procedure for the first time. Inorganic electrolytes (sodium salts) were shown to be coacervation agents, due to their salting-out property in solution of sodium di(2-ethylhexyl)phosphate, obtained by deprotonation of the acid. The physico-chemical properties of the newly synthesised solvents were studied. Sodium carbonate and sodium phosphate were found to be the most suitable coacervation agents, due to their alkaline nature and low viscosity of the supramolecular solvent phases they produce. The extraction ability of the novel solvent was demonstrated in liquid-phase microextraction of a colored derivative of antipyrine from saliva for further spectrophotometric determination. The extraction recovery was found to be 70 %. The proposed green sample preparation technique enabled the exclusion of traditional toxic solvents and reduction of reagent consumption. The satisfactory analytical performance of the procedure was validated with real sample analysis. The calibration graph was linear over the concentration range of 0.03 to 0.5 mmol/L. The limit of detection (3σ) and limit of quantification (10σ), calculated from blank tests, were 0.01 and 0.03 mmol/L, respectively.