Non-Canonical Targets of MicroRNAs: Role in Transcriptional Regulation, Disease Pathogenesis and Potential for Therapeutic Targets.

MicroRNAs are a class of regulatory, non-coding small ribonucleic acid (RNA) molecules found in eukaryotes. Dysregulated expression of microRNAs can lead to downregulation or upregulation of their target gene. In general, microRNAs bind with the Argonaute protein and its interacting partners to form a silencing complex. This silencing complex binds with fully or partial complementary sequences in the 3'-UTR of their cognate target mRNAs and leads to degradation of the transcripts or translational inhibition, respectively. However, recent developments point towards the ability of these microRNAs to bind to the promoters, enhancers or coding sequences, leading to upregulation of their target genes. This review briefly summarizes the various non-canonical binding sites of microRNA and their regulatory roles in various diseased conditions.

An Oncocytic Variant of Papillary Thyroid Carcinoma Mimicking As Metastatic Adenocarcinoma: A Diagnostic Challenge.

Papillary thyroid carcinoma is the most common type of thyroid carcinoma, diagnosed on the basis of a predefined set of distinctive nuclear features. There are about 15 known variants of papillary thyroid carcinoma, and the oncocytic variant is not one of the commonly encountered prototypic conventional papillary thyroid carcinoma. We hereby report an unusual case of a 48-year-old woman presenting with thyroid swelling, which proved to be a diagnostic crisis.

Modelling potential human exposure to the urease inhibitor NBPT through the environment-food pathway.

The urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) has recently attracted a lot of attention attributing to its efficiency in reducing ammonia loss from urea fertiliser applied to temperate grassland soils. Ammonia gas lost to the environment causes soil acidification, eutrophication and contributes to global warming through increased greenhouse gas emissions and ozone layer depletion. The active chemical NBPT blocks the soil microbial enzyme (urease) and reduces ammonia emission. Furthermore, NBPT's use in agriculture might benefit farmers by reducing reliance on expensive nitrate fertiliser and aiding in a shift to more urea-based fertiliser (using NBPT co-applied with urea is more cost-effective). The present study was carried out to characterise the potential transfer of NBPT from grass to liquid milk and compute the associated human health risks. Using probabilistic risk assessment techniques, an exposure assessment model was developed to calculate the Estimated Daily Intake (EDI) of NBPT from milk, following co-application of NBPT with a urea N-fertiliser. Results show that the predicted mean concentration of NBPT in milk is 2.5 × 10-8 mg NBPT/kg milk, while the mean daily intake (EDI) of NBPT is 5 × 10-11 mg NBPT /kg BW/day). Back-calculations revealed that, under the studied conditions, for the EDI to exceed ADI of 3 × 10-2 mg NBPT/kg BW/ day, the NBPT application rate would need to exceed the NBPT fertiliser limit (0.09-0.2% by mass of urea nitrogen) set in the Commission Regulation (EC) No 1107/2008, and the bio-transfer factor would need to be over 100% (implausible). Sensitivity analysis revealed soil pH (SPH), phytoaccumulation factor (PF), NBPT permissible levels in fertiliser (NBPT%), pasture cover (P), and grazing rotation length (t) as critical factors influencing the EDI of NBPT. The present study concludes that NBPT presents negligible risk to human health under the conditions and assumptions studied.

Measurement of grass uptake of the urease inhibitor NBPT and of the nitrification inhibitor dicyandiamide co-applied with granular urea.

Grass uptake and phytoaccumulation factors of N-(n-butyl) thiophosphoric triamide (NBPT) and dicyandiamide (DCD) were quantified. Following the application of urea fertilizer treated with the inhibitors in Irish grassland, grass samples were collected at 5, 10, 15, 20, and 30 day time intervals following five application cycles. Uptake of NBPT by grass was below the limit of quantitation of the analytical method (0.010 mg NBPT kg-1). Dicyandiamide concentrations in grass ranged from 0.004 to 28 mg kg-1 with the highest concentrations measured on days 5 and 10. A reducing trend in concentration was found after day 15. The DCD phytoaccumulation factor was ranged from 0.004% to 1.1% showing that DCD can be taken up by grass at low levels when co-applied with granular urea. In contrast, NBPT was not detected indicating that grass uptake is unlikely when co-applied with granular urea fertilizer. The contrasting results are likely due to very different longevity of DCD and NBPT along with the much lower rate of NBPT, which is used compared with DCD.

Functional response of an egg parasitoid, Trichogramma chilonis Ishii to sublethal imidacloprid exposure.

BACKGROUND: The effectiveness of a biological control agent depends on how well it can control pests and how compatible it is with pesticides. Therefore, we reported the multigenerational effect of a commonly used insecticide, imidacloprid, on the functional response of a widely acclaimed egg parasitoid, Trichogramma chilonis Ishii, to different densities of the host Corcyra cephalonica Stainton eggs. The study investigated the outcomes of the median lethal concentration (LC50 ) and sublethal concentrations (LC5 , LC30 ), along with control treatments for five continuous generations (F1 to F5 ). RESULTS: The results showed that the F5 generation of LC30 , both of the F1 and F5 generations of LC50 , and the control all had a Type II functional response. A Type I functional response was exhibited for the F1 generation of LC30 and both generations of LC5 . The attack rate on host eggs treated with LC5 and LC30 did not change (decrease) with the shift in the type of functional response as compared to the control. A significant increase in the searching efficiency (a) was observed in the later generation (F5 ) under the exposure of LC5 and LC30 imidacloprid concentrations. A lower handling time (Th ) in both generations of the LC5 followed by LC30 treated individuals was observed when compared with the control and LC50 treatments. The per capita parasitization efficiency (1/Th ) and the rate of parasitization per handling time (a/Th ) were also considerably higher in both the generations of LC5 and LC30 than in the control and LC50 , thereby implying positive effects of imidacloprid on the parasitization potential of T. chilonis. CONCLUSION: Altogether, these multigenerational outcomes on the functional response of T. chilonis could be leveraged to control the intractable lepidopteran pests under the mild exposure of imidacloprid in integrated pest management (IPM) programs as well as in the mass rearing of the parasitoid, T. chilonis. © 2023 Society of Chemical Industry.

Sublethal phosphine fumigation induces transgenerational hormesis in a factitious host, Corcyra cephalonica.

BACKGROUND: The rice moth, Corcyra cephalonica (Stainton) (Lepidoptera: Pyralidae) is a pest of stored grains and widely used as a factitious host during the mass rearing of several natural enemies of crop pests. Hormesis is well-documented in pest insects, to some extent in natural enemies of pests. RESULTS: We report transgenerational stimulatory effects of the widely used fumigant, phosphine. The study reports the consequences of sublethal, low lethal and median lethal concentrations (LC5 , LC25 and LC50 ) and untreated control for two sequential generations of the species (G1 to G2 ). In this study, we investigated the life-history traits, nutrient reserves (protein, lipid and carbohydrate) and larval gut microbiome (using 16 s rRNA V3-V4 metagenomics sequencing) of C. cephalonica. Stimulatory effects were observed for various biological traits of C. cephalonica, notably adult longevity, emergence and increased egg hatchability when exposed to LC5 of phosphine. The total protein, lipid and carbohydrate contents of C. cephalonica also were found to be significantly increased by LC5 in both generations. The microbial diversity of LC5 treated larval gut was higher and found to be different from the rest of the treatments. This is the first report showing hormesis to a fumigant insecticide. CONCLUSION: Our findings increase knowledge on the interaction between hormesis, nutrient reserves and gut bacteria in C. cephalonica exposed to insecticides. Overall, the present study establishes phosphine-induced hormesis at LC5 in the host C. cephalonica, which might help improve the quality of mass rearing of various natural enemies. © 2023 Society of Chemical Industry.

Plant Secondary Metabolites as Defense Tools against Herbivores for Sustainable Crop Protection.

Plants have evolved several adaptive strategies through physiological changes in response to herbivore attacks. Plant secondary metabolites (PSMs) are synthesized to provide defensive functions and regulate defense signaling pathways to safeguard plants against herbivores. Herbivore injury initiates complex reactions which ultimately lead to synthesis and accumulation of PSMs. The biosynthesis of these metabolites is regulated by the interplay of signaling molecules comprising phytohormones. Plant volatile metabolites are released upon herbivore attack and are capable of directly inducing or priming hormonal defense signaling pathways. Secondary metabolites enable plants to quickly detect herbivore attacks and respond in a timely way in a rapidly changing scenario of pest and environment. Several studies have suggested that the potential for adaptation and/or resistance by insect herbivores to secondary metabolites is limited. These metabolites cause direct toxicity to insect pests, stimulate antixenosis mechanisms in plants to insect herbivores, and, by recruiting herbivore natural enemies, indirectly protect the plants. Herbivores adapt to secondary metabolites by the up/down regulation of sensory genes, and sequestration or detoxification of toxic metabolites. PSMs modulate multi-trophic interactions involving host plants, herbivores, natural enemies and pollinators. Although the role of secondary metabolites in plant-pollinator interplay has been little explored, several reports suggest that both plants and pollinators are mutually benefited. Molecular insights into the regulatory proteins and genes involved in the biosynthesis of secondary metabolites will pave the way for the metabolic engineering of biosynthetic pathway intermediates for improving plant tolerance to herbivores. This review throws light on the role of PSMs in modulating multi-trophic interactions, contributing to the knowledge of plant-herbivore interactions to enable their management in an eco-friendly and sustainable manner.

Current knowledge on urease and nitrification inhibitors technology and their safety.

OBJECTIVE: Urea is one of the most widely used commercial fertilisers worldwide due to its high N density and cost effectiveness. However, it can be lost in the form of gaseous ammonia and other greenhouse gas (GHG) emissions which can potentially lead to environmental pollution. Farmers are compelled to apply more urea to account for those losses, thereby increasing their expenditure on fertilization. The objective of this paper is to present a literature review on current knowledge regarding inhibitor technologies such as urease inhibitor; n-(N-butyl) thiophosphoric triamide (NBPT), and nitrification inhibitor; dicyandiamide (DCD). METHODS: A thorough review of all the scientific literature was carried out and a proposed risk assessment framework developed. RESULTS: The study showed that the urease inhibitor NBPT significantly reduced NH3 loss from urea. However, concerns about NBPT safety to human health had been raised when the nitrification inhibitor DCD appeared as a residue in milk. This article presents a risk assessment framework for evaluating human exposure to chemicals like NBPT or DCD, following the consumption of foods of animal origin (e.g. milk) from cows grazing on inhibitor-treated pasture. CONCLUSION: The EU's target of a 40% reduction of greenhouse gas emissions by 2030 can be aided by using NBPT as part of an overall suite of solutions. A comprehensive risk assessment is advised for effective evaluation of potential risks from exposure to these inhibitors.