Mode of action Criteria for selection of the critical effect and safe dose range for PFOA by the Alliance for risk assessment.

In response to the current disparity in risk assessment values for PFOA from different agencies and countries, an international effort facilitated by the Alliance for Risk Assessment (ARA) was recently undertaken to characterize the range of scientifically supportable safe dose estimates. In this assessment (Burgoon et al., 2023), an evaluation of the evidence regarding the potential modes of action (MOA) for PFOA toxicity was performed first, so that it could be used to inform subsequent decisions regarding potential critical effects and studies.

Emerging antibiotic and heavy metal resistance in spore-forming bacteria from pig manure, manure slurry and fertilized soil.

Spore-forming bacteria (SFB), like Bacillus, are the gram-positive bacteria with broad-spectrum activity that is one of the commonly used strains of probiotics. However, these bacteria also have significant resistance. In this study, we systematically investigated pig manure, manure slurry and soil by 16S rRNA high-throughput sequencing and traditional culture techniques.

Predicting rainfall using machine learning, deep learning, and time series models across an altitudinal gradient in the North-Western Himalayas.

Predicting rainfall is a challenging and critical task due to its significant impact on society. Timely and accurate predictions are essential for minimizing human and financial losses. The dependence of approximately 60% of agricultural land in India on monsoon rainfall implies the crucial nature of accurate rainfall prediction.

Treatment intensification with radium-223 plus enzalutamide in patients with metastatic castration-resistant prostate cancer.

Several life-prolonging therapies with diverse mechanisms of action (MoA) are available for the treatment of metastatic hormone-sensitive/castration-resistant prostate cancer, with many patients requiring multiple lines of therapy. Nevertheless, treatment optimization to further delay disease progression and improve overall survival remains an unmet need. Despite the number of agents with differing MoAs approved for advanced prostate cancer, many patients receive only one or two life-prolonging therapies.

Biomass-Derived Organonanomaterials as Contrast Agents for Efficient Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is a popular imaging tool that is valuable for the early detection and monitoring of malignancies because it does not involve radiation and is noninvasive. Metal-based contrast agents (CAs) are commonly used in clinical settings despite concerns about the toxicity of free metals. Therefore, finding alternative nontoxic imaging probes is vital.

Xylene: weight of evidence approach case study to determine the need for an extended one generation reproductive study with a developmental neurotoxicity animal cohort.

Xylene is a high production volume chemical that is widely used as a solvent and polymer precursor, and is currently undergoing substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH). Xylenes recently received testing decisions on one-generation reproductive toxicity (EOGRT) studies with additional developmental neurotoxicity (DNT) cohorts for each of the three isomers. Xylene presents a unique opportunity to investigate the need for additional animal DNT toxicology testing because it is a legacy industrial chemical for which a significant amount of animal and human data already exists on its toxicity profile, including central nervous system effects.

Impact of the COVID-19 pandemic on medical office assistants (MOAs) Working in Primary Care: A Qualitative Study.

Background: Medical Office Assistants (MOAs), also known as receptionists and clerks, are front line workers and the most accessible member of the primary care team. Historically, their contributions to primary care have been unrecognised and undervalued. The COVID-19 pandemic put pressure on existing roles and systems in primary care: how MOAs adapted is unknown.

MurA-catalyzed synthesis of 5-enolpyruvylshikimate-3-phosphate confers glyphosate tolerance in bryophytes.

Glyphosate is a broad-spectrum herbicide that kills most vascular plant weeds but is ineffective against many bryophytes. Glyphosate competitively inhibits the enolpyruvyl transferase enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS catalyzes the production of 5-enolpyruvylshikimate-3-phosphate (EPSP)-an intermediate in the shikimate pathway-from shikimate-3-phosphate (S3P) and phosphoenolpyruvate (PEP) substrates.

Toward New Therapeutics for Visceral Leishmaniasis: Efficacy and Mechanism of Action of Amides Inspired by Gibbilimbol B.

The problems with current strategies to control canine visceral Leishmaniasis (CVL), which include the euthanasia of infected animals, and also the toxicity of the drugs currently used in human treatments for CVL, add urgency to the search for new therapeutic agents. This study aimed to evaluate the activity against of 12 amides that are chemically inspired by gibbilimbol B, a bioactive natural product that was initially obtained from . Three of these compounds--(2-ethylhexyl)-4-chlorobenzamide (), -(2-ethylhexyl)-4-nitrobenzamide (), and -(2-ethylhexyl)-4-(-butyl)benzamide () -demonstrated activity against the intracellular amastigotes without toxicity to mammalian host cells (CC > 200 μM); compounds , , and resulted in EC values of 12.

Neuropeptide Bursicon and its receptor-mediated the transition from summer-form to winter-form of .

Seasonal polyphenism enables organisms to adapt to environmental challenges by increasing phenotypic diversity. exhibits remarkable seasonal polyphenism, specifically in the form of summer-form and winter-form, which have distinct morphological phenotypes. Previous research has shown that low temperature and the temperature receptor regulate the transition from summer-form to winter-form in by impacting cuticle content and thickness.

Antifungal Effects and Postharvest Diseases Control Potential of , -2, 4-Nonadienal against .

Pathogenic microorganisms are a significant cause of food spoilage, adversely affecting both product quality and human health. This study evaluated the antifungal activities of 34 aldehydes against foodborne and plant pathogenic fungi, identifying 8 promising lead compounds. Among them, , -2, 4-nonadienal exhibited optimal effects against with an EC of 11.

Promoting tomato resilience: effects of ascorbic acid and sulfur-treated biochar in saline and non-saline cultivation environments.

The resilience of tomato plants under different cultivation environments, particularly saline and non-saline conditions, was investigated by applying various treatments, including 0.5% Ascorbic Acid (AsA) and 1% Sulphur-treated Biochar (BS). The study evaluated parameters such as fruit length, diameter, yield per plant and pot, Total Soluble Solids (TSS) content, chlorophyll content, electrolyte leakage, enzyme activities (Superoxide Dismutase - SOD, Peroxidase - POD, Catalase - CAT), and nutrient content (Nitrogen - N%, Phosphorus - P%, Potassium - K%).

The effects of Remdesivir's functional groups on its antiviral potency and resistance against the SARS-CoV-2 polymerase.

Remdesivir (RDV, Veklury®) is the first FDA-approved antiviral treatment for COVID-19. It is a nucleotide analogue (NA) carrying a 1'-cyano (1'-CN) group on the ribose and a pseudo-adenine nucleobase whose contributions to the mode of action (MoA) are not clear. Here, we dissect these independent contributions by employing RDV-TP analogues.

Aristolochic acid-induced dyslipidemia and hepatotoxicity: The potential role of FXR and AHR receptors.

Aristolochic acids (AAs) represent a class of nitrophenanthrene carboxylic acids naturally existing or accidentally mixed in herbal medicines or crops, which have long been recognized for causing nephropathy. Recently, the linkage between AAs and liver injury has become a concern; however, the current understanding of the mechanism or mode of action (MOA) is limited. In the present study, we investigated nuclear receptor-mediated MOA associated with AAs-induced liver injury including dyslipidemia and hepatotoxicity.

Combating Fungal Infections and Resistance with a Dual-Mechanism Luminogen to Disrupt Membrane Integrity and Induce DNA Damage.

Antifungal drug resistance is a critical concern, demanding innovative therapeutic solutions. The dual-targeting mechanism of action (MoA), as an effective strategy to reduce drug resistance, has been validated in the design of antibacterial agents. However, the structural similarities between mammalian and fungal cells complicate the development of such a strategy for antifungal agents as the selectivity can be compromised.

Valifenalate-induced non-adverse thyroid changes via adaptive induction of uridine 5'-diphospho-glucuronosyltransferase (UGT) in the liver of dogs and rats but not humans.

Some rat and dog toxicology studies with the fungicide valifenalate showed minimal, non-adverse thyroid changes, mostly above the maximum tolerated dose, and concomitantly with liver effects. This publication describes their mode of action (MOA), combining in vivo and new approach methodologies (NAMs), in a weight of evidence approach. Data demonstrate a MOA of liver enzyme induction via nuclear receptor CAR/PXR activation, increased thyroxine (T4) metabolism and elevated thyroid stimulating hormone (TSH) level, leading to thyroid follicular cell hypertrophy and increased thyroid weight.

The mode of toxic action of ionic liquids: Narrowing down possibilities using high-throughput, in vitro cell-based bioassays.

Growing concerns about the environmental impact of ionic liquids (ILs) have spurred research into their (eco)toxic effects, but studies on their mode of toxic action (MOA) still remain limited. However, understanding the MOA and identifying structural features responsible for enhanced toxicity is crucial for characterising the hazard and designing safer alternatives. Therefore, 45 ILs, with systematically varied chemical structures, were tested for cytotoxicity and two specific endpoints in reporter gene assays targeting the Nrf2-ARE mediated oxidative stress response (AREc32) and aryl hydrocarbon receptor activation (AhR-CALUX).

The Arabidopsis E3 ubiquitin ligase DOA10A promotes localization of abscisic acid (ABA) receptors to the membrane through mono-ubiquitination in ABA signaling.

The endoplasmic reticulum-associated degradation (ERAD) system eliminates misfolded and short-lived proteins to maintain physiological homeostasis in the cell. We have previously reported that ERAD is involved in salt tolerance in Arabidopsis. Given the central role of the phytohormone abscisic acid (ABA) in plant stress responses, we sought to identify potential intersections between the ABA and the ERAD pathways in plant stress response.

Biochar addition enhances remediation efficiency and rapeseed yield in copper-contaminated soil.

Introduction: Soil contamination with copper (Cu) threatens ecological security and human health. Rapeseed demonstrates potential in remediating copper-contaminated soil, and biochar-assisted phytoremediation is increasingly being employed to improve remediation efficiency. However, the combined application of them has not been thoroughly studied in terms of the synergistic effects and the mechanisms of their interaction.

A receptor kinase senses sterol by coupling with elicitins in auxotrophic .

Sterols are vital nutrients and signals for eukaryotic organisms. Mammalian cells are known to sense and respond to sterol status changes to maintain them within strict limits, a process associated with various human diseases. However, this process is not understood in oomycete pathogens, most of which are sterol auxotrophic and must obtain sterols from host plants.