High Toxicity Research Articles

Stereotactic central/core ablative radiation therapy: results of a phase I study of a novel strategy to treat bulky tumor

PurposeBulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART.Methods and materialsWe defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV’s border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents.Results21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 14–85) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009).ConclusionSCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.

Polymer chain extenders induce significant toxicity through DAF-16 and SKN-1 pathways in Caenorhabditis elegans: A comparative analysis

Polymer chain extenders, commonly used in plastic production, have garnered increasing attention due to their potential environmental impacts. However, a comprehensive understanding of their ecological risks remains largely unknown. In this study, we employed the model organism Caenorhabditis elegans to investigate toxicological profiles of ten commonly-used chain extenders. Exposure to environmentally relevant concentrations of these chain extenders (ranging from 0.1 µg L−1 to 10 mg L−1) caused significant variations in toxicity. Lethality assays demonstrated the LC50 values ranged from 92.42 µg L−1 to 1553.65 mg L−1, indicating marked differences in acute toxicity. Sublethal exposures could inhibit nematodes’ growth, shorten lifespan, and induce locomotor deficits, neuronal damage, and reproductive toxicity. Molecular analyses further elucidated the involvement of the DAF-16 and SKN-1 signaling pathways, as evidenced by upregulated expression of genes including ctl-1,2,3, sod-3, gcs-1, and gst-4. It implicates these pathways in mediating oxidative stress and toxicities induced by chain extenders. Particularly, hexamethylene diisocyanate and diallyl maleate exhibited markedly high toxicity among the chain extenders, as revealed through a comparative analysis of multiple endpoints. These findings demonstrate the potential ecotoxicological risks of polymer chain extenders, and suggest the need for more rigorous environmental safety assessments.

Sensitive Detection and Differentiation of Biologically Active Ricin and Abrin in Complex Matrices via Specific Neutralizing Antibody-Based Cytotoxicity Assay.

Ricin and abrin are highly potent plant-derived toxins, categorized as type II ribosome-inactivating proteins. High toxicity, accessibility, and the lack of effective countermeasures make them potential agents in bioterrorism and biowarfare, posing significant threats to public safety. Despite the existence of many effective analytical strategies for detecting these two lethal toxins, current methods are often hindered by limitations such as insufficient sensitivity, complex sample preparation, and most importantly, the inability to distinguish between biologically active and inactive toxin. In this study, a cytotoxicity assay was developed to detect active ricin and abrin based on their potent cell-killing capability. Among nine human cell lines derived from various organs, HeLa cells exhibited exceptional sensitivity, with limits of detection reaching 0.3 ng/mL and 0.03 ng/mL for ricin and abrin, respectively. Subsequently, toxin-specific neutralizing monoclonal antibodies MIL50 and 10D8 were used to facilitate the precise identification and differentiation of ricin and abrin. The method provides straightforward and sensitive detection in complex matrices including milk, plasma, coffee, orange juice, and tea via a simple serial-dilution procedure without any complex purification and enrichment steps. Furthermore, this assay was successfully applied in the unambiguous identification of active ricin and abrin in samples from OPCW biotoxin exercises.

A robust acid-resistant chelating polymer for enhanced stabilization of lead ions in fly ash

Fly ash derived from municipal solid waste incinerators (MSWIs) harbors significant quantities of heavy metals with high leaching toxicity, resulting in detrimental environmental effects. Pb2+ in fly ash is the ion most likely to exceed permissible levels. However, chemical stabilization methods demonstrate poor efficacy in stabilizing Pb2+ under acidic conditions. Herein, we have developed a robust acid-resistant chelating polymer (25DTF) for enhanced stabilization of Pb2+ in fly ash. 25DTF was synthesized through the reaction of formaldehyde with 2,5-dithiourea. 25DTF exhibited remarkable chelation efficiency, nearing 100%, for Pb2+ in fly ash. 25DTF demonstrated exceptional chelation efficiency, surpassing 99.9%, when interacting with Pb2+ in fly ash at pH ≤ 7. Even under acidic conditions, 25DTF effectively prevented the secondary dissolution of Pb2+. Additionally, it indicated outstanding Pb2+ chelation efficiency across diverse regions of China. The 25DTF chelating agent shows considerable potential in alleviating metal ion contamination in soil, wastewater, and urban environmental management, thereby fostering advancements in environmental stewardship.

#99 Clinical characteristics and outcomes of PTLD after kidney transplant: a single center experience

Abstract Background and Aims Post-Transplant Lymphoproliferative Disorder (PTLD) is a serious and potentially fatal complication of immunosuppression in kidney transplantation. Given the rarity of this entity, a high index of suspicion is necessary. We aimed to review the incidence, clinical presentation, histological subtypes, treatment, patient and graft survival of PTLD in kidney transplant patients in our unit. Methods Observational retrospective study, including adults diagnosed with PTLD between 1998 and 2023 in a Kidney Transplantation Center. Results Of 1390 kidney transplant recipients, 4 (0.3%) developed PTLD with a mean age of 52 ± 12.5 years. All cases were late-onset, occurring one year after transplantation with a median time from transplantation to diagnosis of 16.7 ± 7.3 years (range: 5-22 years). Of these, none had EBV donor/recipient mismatch. Two patients had prior rejection episodes (one patient, acute T cell-mediated rejection and the other patient, acute T cell-mediated rejection and active antibody mediated rejection). Clinical presentation was variable. Non-specific constitutional symptoms such as fever, fatigue and night sweats were present in all patients. Organ-specific symptoms were also present: lumbar pain in one patient with bone involvement, and delirium and lethargy in two patients with central nervous system involvement. Laboratory analyses revealed an increase in serum LDH in all patients. The primary sites of involvement were central nervous system (50%), lymph nodes (25%) and bone (25%). At PTLD diagnosis, immunosuppression included: tacrolimus (100%), mycophenolate mofetil (75%), low-dose of steroids (50%) and everolimus (25%). Regarding histologic classification, 75% were monomorphic and 25% polymorphic. In the monomorphic group, all patients had Diffuse Large B Cell Lymphoma (CD20 positive). In the polymorphic group, the patient had a Mixed Cellularity Classic Hodgkin Lymphoma (CD20 negative). Immunosuppression therapy was reduced in all patients with discontinuation of mycophenolate mofetil and tacrolimus. In the patient who was taking everolimus, the dose was increased due to the potential clinical antitumor effects of mTOR inhibition. Additional therapies included, rituximab in monotherapy or in combination with chemotherapy (R-CHOP) in the monomorphic group. Palliative measures were selected for one patient of this group due to advanced disease. The patient with Mixed Cellularity Classic Hodgkin Lymphoma (CD20 negative) did chemotherapy with ABVD. None of the patients underwent surgery or radiation therapy. Two patients needed dialysis. Three patients died in the first four weeks after PTLD diagnosis, all due to infectious complications. Patient survival was 25% one year after diagnosis. Conclusions Although the incidence of PTLD was low following kidney transplantation, its impact was significant in kidney graft and overall patient survival. Given the poor prognosis, new therapies combining high efficacy and low toxicity are an urgent unmet medical need in this field.

Functionalized Gold Nanoparticles and Halogen Bonding Interactions Involving Fentanyl and Fentanyl Derivatives.

Fentanyl (FTN) and synthetic analogs of FTN continue to ravage populations across the globe, including in the United States where opioids are increasingly being used and abused and are causing a staggering and growing number of overdose deaths each year. This growing pandemic is worsened by the ease with which FTN can be derivatized into numerous derivatives. Understanding the chemical properties/behaviors of the FTN class of compounds is critical for developing effective chemical detection schemes using nanoparticles (NPs) to optimize important chemical interactions. Halogen bonding (XB) is an intermolecular interaction between a polarized halogen atom on a molecule and e--rich sites on another molecule, the latter of which is present at two or more sites on most fentanyl-type structures. Density functional theory (DFT) is used to identify these XB acceptor sites on different FTN derivatives. The high toxicity of these compounds necessitated a "fragmentation" strategy where smaller, non-toxic molecules resembling parts of the opioids acted as mimics of XB acceptor sites present on intact FTN and its derivatives. DFT of the fragments' interactions informed solution measurements of XB using 19F NMR titrations as well as electrochemical measurements of XB at self-assembled monolayer (SAM)-modified electrodes featuring XB donor ligands. Gold NPs, known as monolayer-protected clusters (MPCs), were also functionalized with strong XB donor ligands and assembled into films, and their interactions with FTN "fragments" were studied using voltammetry. Ultimately, spectroscopy and TEM analysis were combined to study whole-molecule FTN interactions with the functionalized MPCs in solution. The results suggested that the strongest XB interaction site on FTN, while common to most of the drug's derivatives, is not strong enough to induce NP-aggregation detection but may be better exploited in sensing schemes involving films.

Highly Efficient Flexible Photodetectors Based on Pb-Free CsBi3I10 Perovskites.

Perovskites have made remarkable advancements in optoelectronics owing to their high light absorption coefficient, tunable bandgap, and long charge diffusion. Nonetheless, the practical applications of Pb-based perovskites have been hindered by the instability and toxicity of Pb, especially in flexible electronics, which require high biosecurity and low toxicity. Hence, the development of stable Pb-free perovskite materials has gained increasing attention. In this study, we synthesized stable CsBi3I10 Pb-free perovskites outside the glovebox and improved the optoelectronic and mechanical performances of the CsBi3I10-based flexible devices through polyvinylcarbazole (PVK) doping. Flexible photodetectors with the device structure of PET/ITO/PEDOT:PSS/CsBi3I10:PVK/Au was fabricated. The results indicated that the introduction of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) reduced the surface roughness of the flexible PET substrate, while PVK doping further improved the surface smoothness of CsBi3I10 thin films, thereby enhancing the interfacial charge transportation. Moreover, PEDOT:PSS and PVK acted as stepwise hole transport layers in the photodetectors. The device demonstrated a maximum responsivity of 0.3 A/W, detectivity of 2.6 × 1011 Jones, and a response time of 102 μs at 650 nm. After subjecting it to 1000 bending tests, the light current retained 80% of its initial value. This study presents a universally applicable method for controlling the surface morphology of a flexible perovskite thin film.

Biotechnological approaches in the production of plant secondary metabolites for treating human viral diseases: Prospects and challenges

Over the last couple of decades, three highly pathogenic and deadly human coronaviruses have posed dreadful impacts on human life, namely SARS-CoV, MERS-CoV and SARS-CoV-2. In addition, many other viral diseases also affect various aspects of human well-being such as lifestyles and socio-economic conditions. Therefore, research on developing antiviral drugs should be progressively carried out to rapidly prevent or reduce the severity of infection for the current and future emerging infection with pandemic potential. Conventional antiviral drugs have been associated with high cost, toxicity and resistance issues. The use of medicinal plants and their secondary metabolites (SMs) with potential anti-inflammatory properties garners attention as a safer alternative for treating viral diseases. This review discussed various plant SMs with therapeutic potential for treating viral diseases. Due to various factors including low concentrations of the phytocompounds produced, relying on natural systems for producing medically important SMs is not sustainable. Thus, several biotechnology strategies such as metabolic engineering and genetic modification, in vitro production as well as gene editing to enhance the phytochemical compounds are also highlighted. Future perspectives on the potential of plant-based antiviral drugs as well as other strategies to treat viral diseases in humans are also elaborated. Altogether, this review gives a comprehensive view of the pharmaceutical importance of plant SMs as an alternative approach against viral diseases.

Long-term evaluating the strengthening effects of iron-carbon mediator for coking wastewater treatment in EGSB reactor

Coking wastewater (CWW) treatment is difficult due to its complex composition and high biological toxicity. Iron-carbon mediators was used to enhance the treatment of CWW through iron-carbon microelectrolysis (ICME). The results indicated that the removal rate of COD and phenolic compounds were enhanced by 24.1 % and 23.5 %, while biogas production and methane content were promoted by 50 % and 7 %. Microbial community analysis indicated that iron-carbon mediators had a transformative impact on the reactor's performance and dependability by enriching microorganisms involved in direct and indirect electron transfer, such as Anaerolineae and Methanothrix. The mediator also produced noteworthy gains in LB-EPS and TB-EPS, increasing by roughly 109.3 % and 211.6 %, respectively. PICRISt analysis demonstrated that iron-carbon mediators effectively augment the abundance of functional genes associated with metabolism, Citrate cycle, and EET pathway. This study provides a new approach for CWW treatment.

Identification of a Novel Inhibitor of Cimex lectularius Acetylcholinesterase.

Acetylcholinesterase (AChE) stands as a primary target of commercial insecticides, notably organophosphates and carbamates. Despite their widespread use in agricultural and indoor pest control, concerns over their high toxicity and the emergence of resistance have restricted their efficacy. In this study, we conducted high-throughput virtual screening against both wild-type (WT) and resistant Cimex lectularius AChE utilizing a library encompassing 1 270 000 compounds. From this screening, we identified 100 candidate compounds and subsequently assessed their inhibitory effects on purified AChE enzymes. Among these candidates, AE027 emerged as a potent inhibitor against both WT and resistant AChE, exhibiting IC50 values of 10 and 43 μM, respectively. Moreover, the binding of AE027 significantly stabilized AChE, elevating its melting temperature by approximately 7 °C. Through molecular docking and molecular dynamics simulation, we delineated the binding mode of AE027, revealing its interaction with a site adjacent to the catalytic center, which is distinct from known inhibitors, with differing poses observed between WT and resistant AChE. Notably, the resistance mutation F348Y, positioned at a site directly interfacing with AE027, impedes ligand binding through steric hindrance. Furthermore, we evaluated the toxicity and pharmacokinetic properties of AE027 utilizing bioinformatics tools. These findings lay a crucial foundation for the development of a novel generation of insecticides that can combat both WT and resistant pest populations effectively and safely.

How monoterpene hydrocarbons could be an alternative insecticide for effective control of Lepidoptera defoliators?

In Tunisia, Orgyia trigotephras (Lepidoptera, Erebidae) is considered among the most harmful pests for forests that cause significant damage to kermes oak and its maquis. Thus, the aim of this study was to evaluate the insecticidal effect of essential oils of Eucalyptus camaldulensis, E. kirtoniana, Thymus algerienis and T. capitatus toward the 3rd instar larvae of O. trigotephras. The chemical composition of essential oils was studied using GC-MS. Different concentrations of essential oils were used for contact action and compared to synthetic insecticide deltamethrin as a reference product. The insecticidal effects of the essential oils were evaluated by measuring the lethal time of 50% of larvae (LT50) and the lethal time of 100% of larvae (LT100). Eucalyptus essential oils were found effective when compared with the essential oil of Thymus spp. and deltamethrin. Their high toxicity may be attributed to their richness in monoterpenes hydrocarbons. Compounds belonging to monoterpenes hydrocarbons may constitute an alternative insecticide for controlling Lepidoptera defoliators outbreaks.

Identification and Functional Characterization of a Surfactant-like Protein Region in Flagellin FliC for Stabilizing Selenium Nanoparticles and Enhancing Bioavailability.

Biogenic selenium nanoparticles (SeNPs) are the most favorable Se form for nutritional supplementation due to their high stability, low toxicity, and high activity. However, the interaction between the surface-binding proteins and their stable biogenic SeNPs, as well as their impact on the stability and bioavailability of SeNPs, remains to be understood. In vitro stabilization experiments revealed an amino acid segment (F(235-386)) in Rahnella aquatilis' flagellin FliC, with surfactant-like properties, stabilizing SeNPs under harsh conditions. FliC and F(235-386) were employed as stabilizers to synthesize SeNPs (FliC@SeNPs and F(235-386)@SeNPs), and surface chemistry analysis revealed coordination reactions between the proteins and Se atoms on the surface of SeNPs. Both FliC and F(235-386) enhanced SeNPs uptake in wheat seedlings but reduced it in bacteria and yeast. This study highlights FliC's core function in stabilizing SeNPs and enhancing their bioavailability, paving the way for agricultural and nutritional applications.

Modified zero-valent iron nanoparticles enhanced remediation of PCBs-contaminated soil

The high toxicity and persistence of polychlorinated biphenyls (PCBs) in the environment require effective remediation of PCBs-contaminated soil. This study used polylactic acid (PLA) and polyethylene glycol 4000 (PEG-4000) to modify zero-valent iron nanoparticles (nZVI) and conducted characterization analysis. It was found that when the addition amount of PLA was 2 %, the dispersion of modified nZVI was better. The initial pH and water to soil ratio were subjected to single factor experiments and fitted using RSM response surface methodology. The optimal reaction conditions were obtained as follows: the addition amount was 84 g·kg−1, the initial pH was 5.41, and the optimal removal rate was 74 % when the ratio of water to soil was 1.8:1. PLA and PEG-4000 were biodegradable substances that played crucial roles in enhancing the effectiveness of nZVI for PCBs-contaminated soil. By encapsulating nZVI with PLA, we significantly reduced its oxidation when exposed to air. Additionally, the inclusion of PEG-4000 helped prevent the particles from clumping together. The synergistic effect of them increased the effective reaction of nZVI and PCBs and ultimately leading to more efficient remediation. This study offered a new pathway for the efficient green remediation of PCBs-contaminated soil.

Current advances of chlorinated organics degradation by bioelectrochemical systems: a review.

Chlorinated organic compounds (COCs) are typical refractory organic compounds, having high biological toxicity. These compounds are a type of pervasive pollutants that can be present in polluted soil, air, and various types of waterways, such as groundwater, rivers, and lakes, posing a significant threat to the ecological environment and human health. Bioelectrochemical systems (BESs) are an effective strategy for the degradation of bio-refractory compounds. BESs improve the waste treatment efficiency through the application of weak electrical stimulation. This review discusses the processes of BESs configurations and degradation performances in different environmental media including wastewater, soil, waste gas and groundwater. In addition, the degradation mechanisms and performance-enhancing additives are summarized. The future challenges and perspectives on the development of BES for COCs removal are briefly discussed.

An Evaluation of Long-Term Contaminated Soil from a Manufactured Gas Plant for in Situ Biodegradation Potential and as a Source of Ferrocyanide-Degrading Bacteria

Despite the high abundance and potential toxicity of ferrocyanide in the environment, data on the bioremediation of these complexes in contaminated soils are missing. In this study we isolated forty bacterial species presented in soil highly contaminated with ferrocyanide complexes, originating from a Manufactured Gas Plant (MGP). All bacterial strains were resistant to ferrocyanide (500 mg L−1). Six isolates showed better growth in the presence of ferrocyanide and were able to use it as a sole nitrogen source. One of them was able to assimilate ferrocyanide‐derived nitrogen and carbon. The strains varied in their tolerance to the ferrocyanide. The Minimum Inhibitory Concentration (MIC) values determined in the rich medium ranged from 1400 mg L−1 to 2000 mg L−1 and in all cases were greater than those set on the minimal medium. Molecular analysis revealed that the investigated isolates had the highest similarity to the Bacillus and Rummeliibacillus lineages. Rummeliibacillus was recognized for the first time for its ferrocyanide-degrading potential. Soil samples collected from MGP sites indicated that the overall indigenous population of microorganisms was low. Total cyanide content ranged from 220 mg kg−1 to 346 mg kg−1. Additionally, elevated Pb concentrations and an imbalanced C:N:P ratio were observed. Our study provides new information about the presence of a well-acclimated bacterial community associated with long-term ferrocyanide-contaminated soil. This bacterial community could play an important role in MGP site bioremediation processes and has the potential for application for other bioremediation purposes; however, it is likely limited due to unfavorable environmental conditions.

Emodin nanocapsules inhibit acute pancreatitis by regulating lipid metabolic reprogramming in macrophage polarization

BackgroundEmodin is a chemical compound found in traditional Chinese herbs. It possesses anti-inflammatory and many other pharmacological effects. Our previous study showed that emodin significantly alleviates the inflammation effect of severe acute pancreatitis (SAP). However, its poor solubility, high toxicity and limited pancreas retention time hinder its clinical application. PurposeWe aimed to prepare emodin nanocapsules with improved bioavailability to achieve the controlled release of emodin by targeting macrophages. Further, the mechanism of mannose-conjugated chitosan-coated lipid nanocapsules loaded with emodin (M-CS-E-LNC) in the treatment of SAP was explored. MethodsM-CS-E-LNC were prepared by the phase inversion method with slight modification. The expression of inflammation mediators and the anti-inflammation efficacy of M-CS-E-LNC were examined by ELISA, IHC and IF in macrophage cells and LPS-induced SAP mice. IVIS spectrum imaging and HPLC were applied to explore the controlled release of M-CS-E-LNC in the pancreas. LC-MS/MS was performed for lipidomics analysis of macrophages. Moreover, a vector-based short hairpin RNA (shRNA) method was used to silence CTP1 gene expression in macrophage cells. ResultsThe levels of inflammatory mediators in macrophages were markedly decreased after treatment with M-CS-E-LNC. The same anti-inflammation effects were detected in SAP mouse through the analysis of serum levels of amylase, TNF-α and IL-6. Importantly, M-CS-E-LNC allowed the emodin to selectively accumulate at pancreas and gastrointestinal tissues, thus exhibiting a targeted release. Mechanistically, the M-CS-E-LNC treatment group showed up-regulated expression of the carnitine palmitoyltransferase 1 (CPT1) protein which promoted intracellular long-chain fatty acid transport, thereby promoting the M2 phenotype polarization of macrophages. ConclusionM-CS-E-LNC exhibited significantly improved bioavailability and water solubility, which translated to greater therapeutic effects on macrophage polarization. Our findings also demonstrate, for the first time, that CPT1 may be a new therapeutic target for SAP treatment.

Standard versus fractionated high-dose cisplatin plus radiation for locally advanced head and neck cancer: Results of the CisFRad (GORTEC 2015-02) randomized phase II trial

BackgroundChemoradiotherapy with high-dose cisplatin (HD-Cis: 100 mg/m2 q3w for three cycles) is the standard of care (SOC) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Cumulative delivered dose of cisplatin is prognostic of survival, even beyond 200 mg/m2 but high toxicity compromises its delivery. AimCisplatin fractionation may allow, by decreasing the peak serum concentration, to decrease toxicity. To date, no direct comparison was done of HD-Cis versus fractionated high dose cisplatin (FHD-Cis). MethodsThis is a multi-institutional randomized phase II trial, stratified on postoperative or definitive chemoradiotherapy, comparing HD-Cis to FHD-Cis (25 mg/m2/d d1-4 q3w for 3 cycles) in patients with LA-HNSCC. The primary endpoint was the cumulative delivered cisplatin dose. ResultsBetween December 2015 and April 2018, 124 patients were randomized. Median cisplatin cumulative delivered dose was 291 mg/m2 (IQR: 251;298) in the FHD-Cis arm and 274 mg/m2 (IQR: 198;295) in the HD-Cis arm (P = 0.054). The proportion of patients receiving a third cycle of cisplatin was higher, with a lower proportion of grade 3–4 acute AEs in the FHD-Cis arm compared to the HD-Cis arm: 81 % vs. 64 % (P = 0.04) and 10 % vs. 17 % (P = 0.002), respectively.With a median follow-up of 48 months (IQR: 41;55), locoregional failure rate, PFS and OS were similar between the two arms. ConclusionAlthough the primary endpoint was not met, FHD-Cis allowed more cycles of cisplatin to be delivered with lower toxicity, when compared to SOC. FHD-Cis concurrently with RT is a treatment option which deserves further consideration.

Study of graphene incorporation into ZnO-PVA nanocomposites modified electrode for sensitive detection of cadmium

The presence of heavy metals often causes significant health risks, particularly cadmium, which is known for its high toxicity. In this study, a glassy carbon electrode was successfully modified by incorporating ZnO-PVA-Graphene nanocomposite, leveraging the excellent electrical properties and electron mobility of the material. Comprehensive material analysis, including XRD, confirmed that ZnO maintained its hexagonal wurtzite crystal structure despite the addition of graphene. Moreover, FESEM analysis showed that increasing graphene concentration led to a reduction in ZnO particle size by 85, 68, and 52 nm, respectively, accompanied by a decrease in band gap energy, as verified by UV–Vis measurements. Photoluminescence tests were also conducted and the result showed a noticeable blue shift in ZnO-PVA-Graphene nanocomposites compared to ZnO-PVA, specifically in the near band-edge (NBE) UV emission within the 374–379 nm wavelength range. Through I–V characterization, the optimal graphene concentration for cadmium detection was identified as 1.5 wt% in ZnO-PVA-Graphene nanocomposites, showing an approximate ohmic response. Meanwhile, square-wave voltammetry analysis of cadmium concentrations ranging from 0 to 80 ppm produced a coefficient of determination of 0.98926 and a Limit of Detection (LOD) of 9.88 ppm. These results showed the significant potential of ZnO-PVA-Graphene nanocomposites as a promising material for further development as an effective electrode modifier, enhancing the sensitivity of detection systems.

A smartphone-based fluorescent biosensor with metal-organic framework biocomposites and cotton swabs for the rapid determination of tetrodotoxin in seafood

BackgroundTetrodotoxin (TTX) is a potent neurovirulent marine biotoxin that is present in puffer fish and certain marine animals. It is capable of causing severe neurotoxic symptoms and even death when consumed through contaminated seafood. Due to its high toxicity, developing an effective assay for TTX determination in seafood has significant benefits for food safety and human health. Currently, it remains challenging to achieve on-site determination of TTX in seafood. To facilitate mass on-site assays, more affordable technologies utilizing accessible equipment that require no skilled personnel are needed. ResultsA smartphone-based portable fluorescent biosensor is proposed for TTX determination by using metal-organic framework (MOF) biocomposites and cotton swabs. Oriented antibody (Ab)-decorated and fluorescent quantum dot (QD)-loaded MOF biocomposites (QD@MOF*Ab) are rapidly synthesized for binding targets and fluorescent responses by utilizing the tunability of zinc-based MOF. Moreover, facile Ab-immobilized household cotton swabs are utilized as TTX capture tools. TTX forms sandwich immune complexes with QD@MOF*Ab probes, achieving signal amplification. These probes are excited by a portable device to generate bright fluorescent signals, which can be detected by the naked eye, and TTX quantitative results are obtained using a smartphone. When observed with the naked eye, the limit of detection (LOD) is 0.4 ng/mL, while intelligent quantitation presents an LOD of 0.13 ng/mL at logarithmic concentrations of 0.2–400 ng/mL. SignificanceThis biosensor is convenient to use, and an easy-to-operate analysis is completed within 15 min, thus demonstrating excellent performance in terms of detection speed and portability. Furthermore, it successfully determines TTX contents in puffer fish and clam samples, demonstrating its potential for monitoring seafood. Herein, this work provides a favorable rapid sensing platform that is easily portable.

Design, Synthesis, and Bioactivity of Trifluoroethylthio-Substituted Phenylpyrazole Derivatives.

As the first marketed phenylpyrazole insecticide, fipronil exhibited remarkable broad-spectrum insecticidal activity. However, it poses a significant threat to aquatic organisms and bees due to its high toxicity. Herein, 35 phenylpyrazole derivatives containing a trifluoroethylthio group on the 4 position of the pyrazole ring were designed and synthesized. The predicted physicochemical properties of all of the compounds were within a reasonable range. The biological assay results revealed that compound 7 showed 69.7% lethality against Aedes albopictus (A. albopictus) at the concentration of 0.125 mg/L. Compounds 7, 7g, 8d, and 10j showed superior insecticidal activity for the control of Plutella xylostella (P. xylostella). Notably, compound 7 showed similar insecticidal activity against Aphis craccivora (A. craccivora) compared with fipronil. Potential surface calculation and molecular docking suggested that different lipophilicity and binding models to the Musca domestica (M. domestica) gamma-aminobutyric acid receptors may be responsible for the decreased activity of the tested derivatives. Toxicity tests indicated that compound 8d (LC50 = 14.28 mg/L) induced obviously 14-fold lower toxicity than fipronil (LC50 = 1.05 mg/L) on embryonic-juvenile zebrafish development.