BACKGROUND: Owing to large amounts of synthetic pesticides being extensively and unreasonably used for crop protection, currently, resistance and negative impacts on human health and environment safety have appeared. Therefore, development of potential pesticide candidates is highly urgent. Herein, a series of ester derivatives of osthole were designed and synthesized as pesticidal agents.
RESULTS: Six spatial configurations of 4\'-(p-toluenoyloxy)osthole (4b), 4\'-(m-fluorobenzoyloxy)osthole (4f), 4\'-(p-fluorophenylacetyloxy)osthole (4m), 4\'-(3\'\',4\'\'-methylenedioxybenzoyloxy)osthole (4q), 4\'-formyloxyosthole (4u) and 4\'-acetyloxyosthole (4v) were determined by X-ray mono-crystal diffraction. Compounds 4b, 4\'-(p-chlorobenzoyloxy)osthole (4g), 4\'-(m-chlorobenzoyloxy)osthole (4h), 4\'-(p-bromobenzoyloxy)osthole (4i) and 4\'-(2\'\'-chloropyridin-3\'\'-ylcarbonyloxy)osthole (4p) showed higher insecticidal activity than toosendanin against Mythimna separata Walker; notably, compound 4b displayed 1.8 times insecticidal activity of the precursor osthole. Against Tetranychus cinnabarinus Boisduval, compounds 4g and 4h showed 3.3 and 2.6 times acaricidal activity of osthole, and good control effects in the glasshouse. Scanning electron microscopy assay demonstrated that compound 4g can damage the cuticle layer of T. cinnabarinus resulting in death.
CONCLUSIONS: Compounds 4g and 4h can be further studied as lead pesticidal agents for the management of M. separata and T. cinnabarinus. These results will pave the way for application of osthole derivatives as agrochemicals. © 2024 Society of Chemical Industry.

UNASSIGNED: Communities affected by large scale and long lasting industrial contamination are often keen to understand whether their health has been impaired by such contamination. This requires answers that integrate environmental public health and environmental justice perspectives. At these sites, exposure scenarios from environmental contamination over time by multiple chemicals, often involving different environmental matrices, are complex and challenging to reconstruct.
UNASSIGNED: An approach for describing the health of such communities in association with environmental contamination is presented, with the methods applied across the three domains of environmental contamination, population exposure and toxicology, environmental and social epidemiology, and environmental public health communication. The approach is described with examples from its application to the case study of Porto Torres, a town with a substantial industrially conditioned evolution.
UNASSIGNED: Activities in the field of environmental contamination, population exposure and toxicology focus on the collection and systematization of available contamination data, the identification of priority pollutants based on their toxicological profiles, the qualitative assessment of the likelihood of exposure for the population to priority pollutants and their known health effects. Environmental and social epidemiology methods are applied to describe the health profiles and socioeconomic conditions of the local population, taking into account multiple health outcomes from local information systems and considering specific diseases based on exposure and toxicological assessments. The environmental public health communication methods are directed to produce a communication plan and for its implementation through interaction with local institutional and social actors. The interpretation of health profiles benefits from a transdisciplinary analysis of the results.
UNASSIGNED: The proposed approach combines the needs of environmental public health and environmental justice allowing the integration of multidisciplinary knowledge to define recommendations for reducing and/or preventing hazardous environmental exposures and adverse health effects, stimulating the interactions between stakeholders, and making the study results more accessible to citizens.

BACKGROUND: Hafnium alloys are employed in medical applications due to their biocompatibility and high corrosion resistance. These alloys have demonstrated osteogenic and antimicrobial activities in surgical implants and have been utilized in the treatment of sarcoma. Additionally, a sensor based on hafnium nanoparticles has been reported for the detection of coronavirus disease 2019. Despite the increasing usage of hafnium, a literature review reveals no studies examining its effects on sperm in both human and animal species.
METHODS: Semen samples were analyzed according to the 2010 World Health Organization (WHO) criteria, and 20 normospermic specimens were included in the study. Three groups were formed: control, hafnium chloride 2 mg/mL, and 4 mg/mL. Motility and viability were assessed in all groups at the 20th and 40th minutes.
RESULTS: The decrease in viable sperm count was found to be significant in the 2 mg/ml HfCl4 group (difference: 12.73 ± 0.8, p<0.001) and the 4 mg/ml HfCl4 group (difference: 41.72 ± 1.34, p<0.001) compared to the control group. A time-dependent decrease in sperm viability was significant across all groups (difference: 8.93 ± 0.59, p<0.001). The decrease in viable sperm count in the 4 mg/ml HfCl4 group was significant when compared to the 2 mg/ml HfCl4 group (difference: 29 ± 1.27, p<0.001). The decrease in total motile sperm count was observed in both the 2 mg/ml HfCl4 group (difference: 12.80 ± 1.30, p<0.001) and the 4 mg/ml HfCl4 group (difference: 35.63 ± 1.12, p<0.001) compared to the control group. Additionally, the decrease in total motile sperm count in the 4 mg/ml HfCl4 group was significant compared to the 2 mg/ml HfCl4 group (difference: 22.80 ± 1.60, p<0.001). A time-dependent decrease in total motile sperm count was also significant (difference: 6.03 ± 0.49, p<0.001).
CONCLUSIONS: The study determined that hafnium chloride negatively affects sperm motility and viability in vitro. These effects may be due to the presence of an acidic environment. It has been demonstrated that instruments containing this element may pose a potential risk.

UNASSIGNED: Alzheimer\'s disease (AD) presents as a widespread neurodegenerative condition impacting over 55 million individuals globally, with an annual rise of 10 million new cases. Despite its staggering prevalence, the absence of a definitive cure establishes the need for a revisit.
UNASSIGNED: We explore the alternative strategies, focusing on the potential therapeutic efficacy of ethanolic extracts derived from the fruit and leaf of Ficus racemosa Linn.
UNASSIGNED: The investigation comprehensively explores pharmacognostic, phytochemical, toxicological, and pharmacological characteristics. In addition to pharmacognostic and physicochemical analyses, toxicological evaluations conducted on experimental animals demonstrated the innocuous nature of the ethanolic extracts (from both fruit and leaf) of F. racemosa, as evidenced by assessments of hemocompatibility, oxidative parameters, and vital organ histology. Phytochemical profiling via GC-MS identified 48 and 80 phytoconstituents in the fruit and leaf extracts, respectively. These constituents were screened for bioactive potential using the \"Lipinski Rule of Five,\" resulting in the selection of 25 and 33 constituents from fruit and leaf extracts, respectively. Subsequent molecular docking studies against the AChE enzyme revealed promising interactions of the selected phytoconstituents. Furthermore, the top-scoring phytoconstituents were subjected to in silico screening to assess their interactions with β- and γ-secretase enzymes, in addition to the AChE enzyme. The cumulative findings substantiate the therapeutic utility of the plant extracts, particularly in the context of AD.
UNASSIGNED: In conclusion, our investigation highlights the promising therapeutic potential of selected phytoconstituents derived from ethanolic extracts of F. racemosa in mitigating AD pathology by targeting key enzyme sites such as AChE, β-, and γ-secretase.

Machine learning (ML) as a novel model-based approach has been used in studying aquatic toxicology in the environmental field. Zebrafish, as an ideal model organism in aquatic toxicology research, has been widely used to study the toxic effects of various pollutants. However, toxicity testing on organisms may cause significant harm, consume considerable time and resources, and raise ethical concerns. Therefore, ML is used in related research to reduce animal experiments and assist researchers in conducting toxicological research. Although ML techniques have matured in various fields, research on ML-based aquatic toxicology is still in its infancy due to the lack of comprehensive large-scale toxicity databases for environmental pollutants and model organisms. Therefore, to better understand the recent research progress of ML in studying the development, behavior, nerve, and genotoxicity of zebrafish, this review mainly focuses on using ML modeling to assess and predict the toxic effects of zebrafish exposure to different toxic chemicals. Meanwhile, the opportunities and challenges faced by ML in the field of toxicology were analyzed. Finally, suggestions and perspectives were proposed for the toxicity studies of ML on zebrafish in future applications.

The aim of this study was to investigate the use of wastewater-based epidemiology (WBE) to estimate heavy metal exposure in Sungai Petani, Malaysia. Atomic absorption spectroscopy was used to detect copper (Cu), nickel (Ni), zinc (Zn), iron (Fe), and cadmium (Cd) in wastewater from eight sewage treatment facilities in Sungai Petani in January 2022. The heavy metal concentrations were measured in both influent and effluent, and the mean concentrations in the wastewater were found to be in the following order: Fe > Ni > Zn > Cd > Cu, with a 100% detection frequency. The results of WBE estimation showed that Fe, Ni, and Zn had the highest estimated per population exposure levels, while Cd had the lowest. Compared to a similar study conducted in Penang, Malaysia, all metals except Cu were found to have higher concentrations in Sungai Petani, even though it is a non-industrial district. These findings highlight the importance of addressing heavy metal contamination in Sungai Petani and implementing effective risk management and prevention strategies.

A SEND toxicology data transformation, harmonization, and analysis platform were created to improve the identification of unique findings related to the intended target, species, and duration of dosing using data from multiple studies. The lack of a standardized digital format for data analysis had impeded large-scale analysis of in vivo toxicology studies. The CDISC SEND standard enables the analysis of data from multiple studies performed by different laboratories. This work describes methods to analyze data and automate cross-study analysis of toxicology studies. Cross-study analysis can be used to understand a single compound\'s toxicity profile across all studies performed and/or to evaluate on-target versus off-target toxicity for multiple compounds intended for the same pharmacological target. This work involved development of data harmonization/transformation strategies to enable cross-study analysis of both numerical and categorical SEND data. Four de-identified SEND datasets from the BioCelerate database were used for the analyses. Toxicity profiles for key organ systems were developed for liver, kidney, male reproductive tract, endocrine system, and hematopoietic system using SEND domains. A cross-study analysis dashboard with a built-in user-defined scoring system was created for custom analyses, including visualizations to evaluate data at the organ system level and drill down into individual animal data. This data analysis provides the tools for scientists to compare toxicity profiles across multiple studies using SEND. A cross-study analysis of 2 different compounds intended for the same pharmacological target is described and the analyses indicate potential on-target effects to liver, kidney, and hematopoietic systems.

Continuous dopaminergic stimulation (CDS) has become an important strategy for the development of drugs to treat Parkinson\'s disease (PD). Rotigotine behenate extended-release microspheres (RBEM) for injection represents a new treatment regime for CDS and is being applied for clinical trial. Our study in cynomolgus monkeys was a 20-week repeat dose toxicity investigation with RBEM at dosages of 90, 180, 360, with a 12-week recovery period. The results observed some irritations in the application site and surrounding tissues in Placebo microspheres and each dose of RBEM, was accompanied with increased white blood count and fibrinogen. RBEM-treated monkeys were additionally noted with a pharmacological action-related decrease in prolactin. These findings showed certain reversibility after the 12-week recovery phase. No clear sex difference was noted in the plasma exposure to rotigotine. The exposure generally increased in a dose-proportional manner. In summary, major toxicological effects are associated with the dopamine agonist-related properties of rotigotine, and the removal of foreign bodies caused by p oly (lactide-co-glycolide) (PLGA)and sodium carboxymethyl cellulose (SCMC), and the no-observed-adverse-effect-level (NOAEL) was 360 mg/kg.

BACKGROUND: Methamphetamine-associated cardiomyopathy (MACM) is a known complication of methamphetamine use; however, risk factors and outcomes of patients with MACM are not well understood.
OBJECTIVE: This study aims to identify risk factors, emergency department (ED) interventions, and outcomes for MACM.
METHODS: This case-control study was conducted between 2012 and 2020 at two academic EDs. ED patients ≥18 years with an index visit that included documented methamphetamine use were included. Patients with documented MACM during follow-up (3 months-3 years) were considered cases (MACM). A control group comprised of patients with documented methamphetamine use but no known MACM was matched at a 2:1 ratio. Logistic regression was used to model risk factors for MACM.
RESULTS: A total of 9833 patients with methamphetamine use were identified. From this, 160 MACM patients were matched to 322 controls. The mean age was 48.4 years, and 143 patients (29.7%) were female. MACM patients were more likely to be admitted on their index visit (45.6% vs. 34.8%, p = 0.021). Significant variables associated with MACM included: admission at the index visit (odds ratio [OR] 1.51), diabetes (OR 3.02), kidney disease (OR 5.47), and pulmonary disease (OR 2.39). MACM patients had more ED visits in the follow-up period (10.1 vs. 7, p = 0.009) and were admitted at a higher rate across all visits (32.5% vs. 15.4%, p = 0.009). Additionally, MACM patients had significantly longer hospital stays than controls (mean 18 additional days, p = 0.009).
CONCLUSIONS: Patients who developed MACM had traditional risk factors for heart failure and experienced significantly more ED visits, more hospitalizations, and longer hospital stays than matched controls.

Propafenone (PPF) belongs to the class 1C antiarrhythmics and can cause electrocardiogram-associated adverse/toxic effects. Cases of PPF intoxication are rarely investigated. We developed a novel and selective GC-MS/MS method for the determination of PPF and its tissue distribution in an intentional fatal poisoning case, which is applicable to PPF quantification in the range of therapeutic to lethal concentrations in complex post-mortem samples. A simple and effective sample pretreatment was applied to all analyzed samples. PPF was determined without the need for dilution, even in highly complex samples containing a wide range of analyte concentrations. Quantification was performed using the standard addition method, developed and validated according to the ICH M10 guidelines. The obtained results indicated that the PPF concentration in the serum from blood taken while alive, before therapy, was the highest ever reported in the literature. Despite the intensive therapy after the patients\' admission, the PPF concentrations in the lungs, spleen, femoral blood and cardiac blood were fatal or abnormally high. On the other hand, the concentrations in the liver and skeletal muscle were lower or approximately the same as observed in cases with therapeutic doses. To the best of our knowledge, the distribution of PPF has not been investigated in fatal intoxication cases and can be helpful in clinical or forensic toxicology.