Comparative transcriptome analysis of doramectin-producing Streptomyces avermitilis N72 and its mutant strains.

Doramectin, an essential animal anthelmintic, is synthesized through the fermentation process of Streptomyces avermitilis. This study delves into the transcriptomic profiles of two strains, namely the doramectin-producing wild-type S. avermitilis N72 and its highly doramectin-producing mutant counterpart, S. avermitilis XY-62. Comparative analysis revealed 860 up-regulated genes and 762 down-regulated genes in the mutant strain, notably impacting the expression of key genes pivotal in doramectin biosynthesis, including aveA1, aveA2, aveA3, aveA4, aveE, and aveBI. These findings shed light on the molecular mechanisms underpinning the heightened doramectin production in S. avermitilis XY-62, presenting promising avenues for optimizing doramectin production processes.

Mosquitocidal effect of ivermectin-treated nettings and sprayed walls on Anopheles gambiae s.s.

Ivermectin (IVM) has been proposed as a new tool for malaria control as it is toxic on vectors feeding on treated humans or cattle. Nevertheless, IVM may have a direct mosquitocidal effect when applied on bed nets or sprayed walls. The potential for IVM application as a new insecticide for long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) was tested in this proof-of-concept study in a laboratory and semi-field environment. Laboratory-reared, insecticide-susceptible Kisumu Anopheles gambiae were exposed to IVM on impregnated netting materials and sprayed plastered- and mud walls using cone bioassays. The results showed a direct mosquitocidal effect of IVM on this mosquito strain as all mosquitoes died by 24 h after exposure to IVM. The effect was slower on the IVM-sprayed walls compared to the treated nettings. Further work to evaluate possibility of IVM as a new insecticide formulation in LLINs and IRS will be required.

Onchocerciasis in the Cameroon-Chad border area after more than 20 years of annual mass ivermectin distribution.

BACKGROUND: The main vectors of onchocerciasis in Africa are Simulium damnosum sensu lato, which transmit the causative agent Onchocerca volvulus. The force of transmission is driven by the vector density, hence influencing the disease prevalence and intensity. Onchocerciasis is currently targeted for elimination using mass drug administration (MDA) of ivermectin, a potent microfilaricide. MDA in Cameroon began in 1987 in the Vina Valley, an endemic cross-border area with Chad, known for high vector densities and precontrol endemicity. Evaluations in 2008-2010 in this area showed ongoing transmission, while border areas in Chad were close to interrupting transmission. This study aimed to evaluate transmission in this area after several rounds of MDA since the last evaluation surveys. METHODS: Black flies were collected by human landing catches at seven border sites in Cameroon, twice a week, from August 2021 to March 2022. A fraction of the flies was dissected for parity assessment and identification of Onchocerca larval stages. The transmission indices were estimated. Black fly larvae were also collected from the breeding sites at the fly catching sites and identified to species level by cytotaxonomy. RESULTS: A total of 14,303 female flies were collected, and 6918 were dissected. Of these, 4421 (64.0%) were parous. The total biting rates were high, reaching up to 16,407 bites/person/study period, and transmission potential (third-stage larvae (L3) from head/all L3) were 367/702, 146/506, 51/55, 20/32, 0/3, 0/0, and 0/0 infective larvae/person, respectively, for Mbere-Tchad, Babidan, Hajam/V5, Gor, Djeing, Touboro, and Koinderi. Infectivity rates (L3 from head) were 16.00, 12.75, 5.15, and 4.07 infective females (L3H)/1000 parous flies for Haijam, Mbere-Tchad, Babidan, and Gor, respectively. These values exceed the World Health Organization (WHO) thresholds of ≤ 20 annual transmission potential (ATP) or < 1 infective female/1000 parous females. The major vectors identified were Simulium damnosum sensu stricto, S. squamosum, and for the first time in the area, S. yahense. CONCLUSIONS: More than 20 years of MDA has not eliminated onchocerciasis in the study area; hence, this area is a potential source of reintroduction of onchocerciasis in Chad and would require alternative treatment strategies. Many factors such as MDA efficiency, effectiveness of ivermectin, and cytospecies composition may be contributing to transmission persistence.

Dietary additive ferulic acid alleviated oxidative stress, inflammation, and apoptosis induced by chronic exposure to avermectin in the liver of common carp (Cyprinus carpio).

Avermectin (AVM) has been utilized extensively in agricultural production since it is a low-toxicity pesticide. However, the pollution caused by its residues to fisheries aquaculture has been neglected. As an abundant polyphenolic substance in plants, ferulic acid (FA) possesses anti-inflammatory and antioxidant effects. The goal of the study is to assess the FA's ability to reduce liver damage in carp brought on by AVM exposure. Four groups of carp were created at random: the control group; the AVM group; the FA group; and the FA + AVM group. On day 30, and the liver tissues of carp were collected and examined for the detection of four items of blood lipid as well as the activity of the antioxidant enzymes catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in carp liver tissues by biochemical kits, and the transcript levels of indicators of oxidative stress, inflammation and apoptosis by qPCR. The results showed that liver injury, inflammation, oxidative stress, and apoptosis were attenuated in the FA + AVM group compared to the AVM group. In summary, dietary addition of FA could ameliorate the hepatotoxicity caused by AVM in carp by alleviating oxidative stress, inflammation, apoptosis in liver tissues.

Lethal and sublethal impacts of membrane-fed ivermectin are concentration dependent in Anopheles coluzzii.

BACKGROUND: Ivermectin is a well-tolerated anthelminthic drug with wide clinical and veterinary applications. It also has lethal and sublethal effects on mosquitoes. Mass drug administration with ivermectin has therefore been suggested as an innovative vector control tool in efforts to curb emerging insecticide resistance and reduce residual malaria transition. To support assessments of the feasibility and efficacy of current and future formulations of ivermectin for vector control, we sought to establish the relationship between ivermectin concentration and its lethal and sublethal impacts in a primary malaria vector. METHODS: The in vitro effects of ivermectin on daily mortality and fecundity, measured by egg production, were assessed up to 14 days post-blood feed in a laboratory colony of Anopheles coluzzii. Mosquitoes were fed ivermectin in blood meals delivered by membrane feeding at one of six concentrations: 0 ng/ml (control), 10 ng/ml, 15 ng/ml, 25 ng/ml, 50 ng/ml, 75 ng/ml, and 100 ng/ml. RESULTS: Ivermectin had a significant effect on mosquito survival in a concentration-dependent manner. The LC50 at 7 days was 19.7 ng/ml. The time to median mortality at ≥ 50 ng/ml was ≤ 4 days, compared to 9.6 days for control, and 6.3-7.6 days for ivermectin concentrations between 10 and 25 ng/ml. Fecundity was also affected; no oviposition was observed in surviving females from the two highest concentration treatment groups. While females exposed to 10 to 50 ng/ml of ivermectin did oviposit, significantly fewer did so in the 50 ng/ml treatment group compared to the control, and they also produced significantly fewer eggs. CONCLUSIONS: Our results showed ivermectin reduced mosquito survival in a concentration-dependent manner and at ≥ 50 ng/ml significantly reduced fecundity in An. coluzzii. Results indicate that levels of ivermectin found in human blood following ingestion of a single 150-200 µg/kg dose would be sufficient to achieve 50% mortality across 7 days; however, fecundity in survivors is unlikely to be affected. At higher doses, a substantial impact on both survival and fecundity is likely. Treating human populations with ivermectin could be used as a supplementary malaria vector control method to kill mosquito populations and supress their reproduction; however strategies to safely maintain mosquitocidal blood levels of ivermectin against all Anopheles species require development.

Impact of ivermectin components on Anopheles dirus and Anopheles minimus mosquito survival.

BACKGROUND: Ivermectin mass drug administration to humans or livestock is a potential vector control tool for malaria elimination. Racemic ivermectin is composed of two components, namely a major component (> 80%; ivermectin B1a), which has an ethyl group at C-26, and a minor component (< 20%; ivermectin B1b), which has a methyl group at C-26. There is no difference between the efficacy of ivermectin B1a and ivermectin B1b efficacy in nematodes, but only ivermectin B1b has been reported to be lethal to snails. The ratios of ivermectin B1a and B1b ratios in ivermectin formulations and tablets can vary between manufacturers and batches. The mosquito-lethal effects of ivermectin B1a and ivermectin B1b have never been assessed. As novel ivermectin formulations are being developed for malaria control, it is important that the mosquito-lethal effects of individual ivermectin B1a and ivermectin B1b compounds be evaluated. METHODS: Racemic ivermectin, ivermectin B1a or ivermectin B1b, respectively, was mixed with human blood at various concentrations, blood-fed to Anopheles dirus sensu stricto and Anopheles minimus sensu stricto mosquitoes, and mortality was observed for 10 days. The ivermectin B1a and B1b ratios from commercially available racemic ivermectin and marketed tablets were assessed by liquid chromatography-mass spectrometry. RESULTS: The results revealed that neither the lethal concentrations that kills 50% (LC50) nor 90% (LC90) of mosquitoes differed between racemic ivermectin, ivermectin B1a or ivermectin B1b for An. dirus or An. minimus, confirming that the individual ivermectin components have equal mosquito-lethal effects. The relative ratios of ivermectin B1a and B1b derived from sourced racemic ivermectin powder were 98.84% and 1.16%, respectively, and the relative ratios for ivermectin B1a and B1b derived from human oral ivermectin tablets were 98.55% and 1.45%, respectively. CONCLUSIONS: The ratio of ivermectin B1a and B1b does not influence the Anopheles mosquito-lethal outcome, an ideal study result as the separation of ivermectin B1a and B1b components at scale is cost prohibitive. Thus, variations in the ratio of ivermectin B1a and B1b between batches and manufacturers, as well as potentially novel formulations for malaria control, should not influence ivermectin mosquito-lethal efficacy.

Ecofriendly Controlled-Release Insecticide Carrier: pH-/Temperature-Responsive Rosin-Derived Hydrogels for Avermectin Delivery against Mythimna separata (Walker).

The exploration of environmentally friendly, less toxic, sustained-release insecticide is increasing with the growing demand for food to meet the requirements of the expanding population. As a sustained-release carrier, the unique, environmentally friendly intelligent responsive hydrogel system is an important factor in improving the efficiency of insecticide utilization and accurate release. In this study, we developed a facile approach for incorporating the natural compound rosin (dehydroabietic acid, DA) and zinc ions (Zn2+) into a poly(N-isopropylacrylamide) (PNIPAM) hydrogel network to construct a controlled-release hydrogel carrier (DA-PNIPAM-Zn2+). Then, the model insecticide avermectin (AVM) was encapsulated in the carrier at a drug loading rate of 36.32% to form AVM@DA-PNIPAM-Zn2+. Surprisingly, the smart controlled carrier exhibited environmental responsiveness, strongly enhanced mechanical properties, self-healing ability, hydrophobicity, and photostability to ensure a balance between environmental friendliness and the precision of the drug release. The release experiments showed that the carboxyl and amide groups in the polymer chains alter the intermolecular forces within the hydrogel meshes and ingredient diffusion by changing temperatures (25 and 40 °C) and pH values (5.8, 7.4, and 8.5), leading to different release behaviors. The insecticidal activity of the AVM@DA-PNIPAM-Zn2+ against oriental armyworms was good, with an effective minimum toxicity toward aquatic animals. Therefore, AVM@DA-PNIPAM-Zn2+ is an effective drug delivery system against oriental armyworms. We anticipate that this ecofriendly, sustainable, smart-response carrier may broaden the utilization rosin and its possible applications in the agricultural sector.

Biomass-Based, Dual Enzyme-Responsive Nanopesticides: Eco-friendly and Efficient Control of Pine Wood Nematode Disease.

Pine wood nematode (PWN) disease is a globally devastating forest disease caused by infestation with PWN, Bursaphelenchus xylophilus, which mainly occurs through the vector insect Japanese pine sawyer (JPS), Monochamus alternatus. PWN disease is notoriously difficult to manage effectively and is known as the "cancer of pine trees." In this study, dual enzyme-responsive nanopesticides (AVM@EC@Pectin) were prepared using nanocoating avermectin (AVM) after modification with natural polymers. The proposed treatment can respond to the cell wall-degrading enzymes secreted by PWNs and vector insects during pine tree infestation to intelligently release pesticides to cut off the transmission and infestation pathways and realize the integrated control of PWN disease. The LC50 value of AVM@EC@Pectin was 11.19 mg/L for PWN and 26.31 mg/L for JPS. The insecticidal activity of AVM@EC@Pectin was higher than that of the commercial emulsifiable concentrate (AVM-EC), and the photostability, adhesion, and target penetration were improved. The half-life (t1/2) of AVM@EC@Pectin was 133.7 min, which is approximately twice that of AVM-EC (68.2 min). Sprayed and injected applications showed that nanopesticides had superior bidirectional transportation, with five-times higher AVM contents detected in the roots relative to those of AVM-EC when sprayed at the top. The safety experiment showed that the proposed treatment had lower toxicity and higher safety for nontarget organisms in the application environment and human cells. This study presents a green, safe, and effective strategy for the integrated management of PWN disease.

Effects of ivermectin on development of Calliphora vicina, Robineau-Desvoidy 1830 (Diptera, Calliphoridae).

Ivermectin is one of the most widely used drugs for parasite control. Previous studies have shown a reduction in the abundance and diversity of "non-target" coprophilous organisms due to the presence of ivermectin (IVM) in bovine faecal matter (FM). Due to its breadth of behavioural habits, Calliphora vicina is a suitable dipteran species to evaluate the effects of IVM in FM. The aim of this work was to evaluate the effect of five concentrations of IVM in FM (3000, 300, 100, 30, and 3 ng/g) on the development of C. vicina. The following endpoints were evaluated: survival (between the first larval stage and emergence of new adults), larval development times to pupation and pupation times to adult, and adult emergence (% sex) and LC50. Sampling was performed from larval hatching at 60 and 120 min and at 3, 4, 5, and 12 h, and every 24 h specimens were weighed until pupae were observed. Data were analysed by ANOVA using a non-parametric Kruskal-Wallis test and as a function of elapsed development time and accumulated degree hours (ADH). Mortality at 3000 and 300 ng/g was 100% and 97%, respectively. There were statistically significant delays in adult emergence time (p = 0.0216) and in the ADH (p = 0.0431) between the control group (C) and 100 ng/g. The LC50 was determined at 5.6 ng/g. These results demonstrate the lethal and sub-lethal effects of IVM on C. vicina, while highlighting the usefulness of this species as a bioindicator for ecotoxicological studies.

Quantifying the fitness effects of resistance alleles with and without anthelmintic selection pressure using Caenorhabditis elegans.

Albendazole (a benzimidazole) and ivermectin (a macrocyclic lactone) are the two most commonly co-administered anthelmintic drugs in mass-drug administration programs worldwide. Despite emerging resistance, we do not fully understand the mechanisms of resistance to these drugs nor the consequences of delivering them in combination. Albendazole resistance has primarily been attributed to variation in the drug target, a beta-tubulin gene. Ivermectin targets glutamate-gated chloride channels (GluCls), but it is unknown whether GluCl genes are involved in ivermectin resistance in nature. Using Caenorhabditis elegans, we defined the fitness costs associated with loss of the drug target genes singly or in combinations of the genes that encode GluCl subunits. We quantified the loss-of-function effects on three traits: (i) multi-generational competitive fitness, (ii) fecundity, and (iii) development. In competitive fitness and development assays, we found that a deletion of the beta-tubulin gene ben-1 conferred albendazole resistance, but ivermectin resistance required the loss of two GluCl genes (avr-14 and avr-15). The fecundity assays revealed that loss of ben-1 did not provide any fitness benefit in albendazole conditions and that no GluCl deletion mutants were resistant to ivermectin. Next, we searched for evidence of multi-drug resistance across the three traits. Loss of ben-1 did not confer resistance to ivermectin, nor did loss of any single GluCl subunit or combination confer resistance to albendazole. Finally, we assessed the development of 124 C. elegans wild strains across six benzimidazoles and seven macrocyclic lactones to identify evidence of multi-drug resistance between the two drug classes and found a strong phenotypic correlation within a drug class but not across drug classes. Because each gene affects various aspects of nematode physiology, these results suggest that it is necessary to assess multiple fitness traits to evaluate how each gene contributes to anthelmintic resistance.

Analysis of lncRNA-related studies of ivermectin-sensitive and -resistant strains of Haemonchus contortus.

In this study, 858 novel long non-coding RNAs (lncRNAs) were predicted as sensitive and resistant strains of Haemonchus contortus to ivermectin. These lncRNAs underwent bioinformatic analysis. In total, 205 lncRNAs significantly differed using log2 (difference multiplicity) > 1 or log2 (difference multiplicity) < - 1 and FDR < 0.05 as the threshold for significant difference analysis. We selected five lncRNAs based on significant differences in expression, cis-regulation, and their association with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. These expressions of lncRNAs, namely MSTRG.12610.1, MSTRG.8169.1, MSTRG.6355.1, MSTRG.980.1, and MSTRG.9045.1, were significantly downregulated. These findings were consistent with the results of transcriptomic sequencing. We further investigated the relative expression of target gene mRNAs and the regulation of mRNA and miRNA, starting with lncRNA cis-regulation of mRNA, and constructed a lncRNA-mRNA-miRNA network regulation. After a series of statistical analyses, we finally screened out UGT8, Unc-116, Fer-related kinase-1, GGPP synthase 1, and sart3, which may be involved in developing drug resistance under the regulation of their corresponding lncRNAs. The findings of this study provide a novel direction for future studies on drug resistance targets.

Prescribing Patterns of Nonrecommended Medications for Children With Acute COVID-19.

OBJECTIVE: Repurposed medications for acute coronavirus disease 2019 (COVID-19) continued to be prescribed after results from rigorous studies and national guidelines discouraged use. We aimed to describe prescribing rates of nonrecommended medications for acute COVID-19 in children, associations with demographic factors, and provider type and specialty. METHODS: In this retrospective cohort of children <18 years in a large United States all-payer claims database, we identified prescriptions within 2 weeks of an acute COVID-19 diagnosis. We calculated prescription rate, performed multivariable logistic regression to identify risk factors, and described prescriber type and specialty during nonrecommended periods defined by national guidelines. RESULTS: We identified 3 082 626 COVID-19 diagnoses in 2 949 118 children between March 7, 2020 and December 31, 2022. Hydroxychloroquine (HCQ) and ivermectin were prescribed in 0.03% and 0.14% of COVID-19 cases, respectively, during nonrecommended periods (after September 12, 2020 for HCQ and February 5, 2021 for ivermectin) with considerable variation by state. Prescription rates were 4 times the national average in Arkansas (HCQ) and Oklahoma (ivermectin). Older age, nonpublic insurance, and emergency department or urgent care visit were associated with increased risk of either prescription. Additionally, residence in nonurban and low-income areas was associated with ivermectin prescription. General practitioners had the highest rates of prescribing. CONCLUSIONS: Although nonrecommended medication prescription rates were low, the overall COVID-19 burden translated into high numbers of ineffective and potentially harmful prescriptions. Understanding overuse patterns can help mitigate downstream consequences of misinformation. Reaching providers and parents with clear evidence-based recommendations is crucial to children's health.

Pharmaceutical messianism and the politics of COVID-19 in the United States.

Throughout the COVID-19 pandemic, public officials in the United States - from the President to governors, mayors, lawmakers, and even school district commissioners - touted unproven treatments for COVID-19 alongside, and sometimes as opposed to, mask and vaccine mandates. Utilising the framework of 'pharmaceutical messianism', our article focuses on three such cures - hydroxychloroquine, ivermectin, and monoclonal antibodies - to explore how pharmaceuticals were mobilised within politicised pandemic discourses. Using the states of Utah, Texas, and Florida as illustrative examples, we make the case for paying attention to pharmaceutical messianism at the subnational and local levels, which can very well determine pandemic responses and outcomes in contexts such as the US where subnational governments have wide autonomy. Moreover, we argue that aside from the affordability of the treatments being studied and the heterodox knowledge claiming their efficacy, the widespread uptake of these cures was also informed by popular medical (including immunological) knowledge, pre-existing attitudes toward 'orthodox' measures like vaccines and masks, and mistrust toward authorities and institutions identified with the 'medical establishment'. Taken together, our case studies affirm the recurrent nature of pharmaceutical messianism in times of health crises - while also refining the concept and exposing its limitations.

A single subcutaneous dose of eprinomectin (Eprecis®) is effective against common gastrointestinal nematodes and lungworms in experimentally infected lactating goats.

BACKGROUND: The health and productivity of dairy goats continue to be impacted by gastrointestinal nematodes (GIN) and lungworms (LW). Eprinomectin (EPN) is frequently selected for treatment because it is generally effective and does not require a milk withdrawal period. However, some factors, such as lactation, can have an impact on EPN pharmacokinetics and potentially its efficacy. To evaluate whether this can alter the efficacy of Eprecis® 2%, an eprinomectin injectable solution, a study was performed in lactating goats using the dose currently registered in cattle, sheep and goats (0.2 mg/kg). METHODS: This study was a blinded, randomized, controlled trial performed according to the VICH guidelines. Eighteen (18) worm-free lactating goats were included and experimentally challenged on day 28 with a mixed culture of infective gastrointestinal and lung nematode larvae (Haemonchus contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta, Dictyocaulus filaria). At D-1, fecal samples were collected to confirm patent infection in all animals. On D0, the goats were randomly allocated into two groups of nine goats; group 1 was treated with Eprecis® 2% at 0.2 mg/kg BW by subcutaneous injection, while group 2 remained untreated. Fecal samples for egg counts were collected from all animals on days 3, 5, 7, 9, 11 and 14. On D14, all goats were killed, and the abomasum, small intestine and lungs were removed, processed and subsampled to record the number and species of worms. RESULTS: The treatment was well tolerated. After treatment, the arithmetic mean FEC decreased in the treated group and remained < 5 EPG until the end of the study, while the arithmetic mean FEC in the control group remained > 849.0 EPG. At D14, goats in the treated group had very limited or zero total worm counts, whereas all animals from the control group had a high worm burden. The measured efficacy was 100.0% against H. contortus and T. colubriformis, 99.9% against T. circumcincta and 98.0% against D. filaria. CONCLUSIONS: Eprinomectin (Eprecis®, 20 mg/ml), administered at the label dose (0.2 mg/kg), is highly effective against gastrointestinal nematodes and lungworms in lactating goats.

Uncovering hidden dangers: The combined toxicity of abamectin and lambda-cyhalothrin on honey bees.

Studying the toxic effects of pesticides on bees has consistently been a prominent area of interest for researchers. Nonetheless, existing research has predominantly concentrated on individual toxicity assessments, leaving a gap in our understanding of mixed toxicity. This study delves into the individual and combined toxic effects of abamectin (ABA) and lambda-cyhalothrin (LCY) on honey bees (Apis mellifera) in laboratory settings. We discovered that ABA (96 h-LC50 value of 0.079 mg/L) exhibited greater acute toxicity to honey bees compared to LCY (96 h-LC50 value of 9.177 mg/L). Moreover, the mixture of ABA and LCY presented an acute antagonistic effect on honey bees. Additionally, our results indicated that exposure to LCY, at medium concentration, led to a reduction in the abundance of gut core bacterium Snodgrassella. However, an increase in the abundance of Bifidobacterium was noted when exposed to a medium concentration of LCY and its mixture with ABA. Transcriptomic analysis revealed significant regulation of certain genes in the medium concentration of all three treatments compared to the control group, primarily enriching in metabolism and immune-related pathways. Following chronic exposure to field-relevant concentrations of ABA, LCY, and their mixture, there were significant alterations in the activities of immunity-related enzyme polyphenol oxidase (PPO) and detoxification enzymes glutathione S-transferase (GST) and carboxylesterase (CarE). Additionally, the expression of four genes (abaecin, cyp9e2, cyp302a1, and GstD1) associated with immune and detoxification metabolism was significantly altered. These findings suggest a potential health risk posed by the insecticides ABA and LCY to honey bees. Despite exhibiting acute antagonistic effect, mixed exposure still induced damage to bees at all levels. This study advances our knowledge of the potential adverse effects of individual or combined exposure to these two pesticides on non-target pollinators and offers crucial guidance for the use of insecticides in agricultural production.

Smart and Sustainable Crop Protection: Design and Evaluation of a Novel α-Amylase-Responsive Nanopesticide for Effective Pest Control.

In this study, an α-amylase-responsive controlled-release formulation was developed by capping polydopamine onto ß-cyclodextrin-modified abamectin-loaded hollow mesoporous silica nanoparticles. The prepared Aba@HMS@CD@PDA were subjected to characterization using various analytical techniques. The findings revealed that Aba@HMS@CD@PDA, featuring a loading rate of 18.8 wt %, displayed noteworthy release behavior of abamectin in the presence of α-amylase. In comparison to abamectin EC, Aba@HMS@CD@PDA displayed a significantly foliar affinity and improved rainfastness on lotus leaves. The results of field trail demonstrated a significantly higher control efficacy against Spodoptera litura Fabricius compared to abamectin EC at all concentrations after 7, 14, and 21 days of spaying, showcasing the remarkable persistence of Aba@HMS@CD@PDA. These results underscore the potential of Aba@HMS@CD@PDA as a novel and persistently effective strategy for sustainable on-demand crop protection. The application of nanopesticides can enhance the effectiveness and efficiency of pesticide utilization, contributing to more sustainable agricultural practices.

Evaluation of genotoxic effect via expression of DNA damage responsive gene induced by ivermectin on MDBK cell line.

Ivermectin (IVM) is an anti-parasitic drug which is used for treating parasitic infestations. It has been used in humans for treating intestinal strongyloidiasis and onchocerciasis however, currently researchers are investigating its potential for treating coronavirus SARS-CoV-2. Due to its broad-spectrum activities, IVM is being used excessively in animals which has generated an interest for researchers to investigate its toxic effects. Cytotoxic and genotoxic effects have been reported in animals due to excessive usage of IVM. Therefore, this study aims to evaluate the cytotoxic and genotoxic effects of IVM on the Madin-Darby-Bovine-Kidney (MDBK) cell line by examining the expression of a DNA damage-responsive gene (OGG1). Cytotoxicity of IVM was tested using an assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), whereas the genotoxicity was evaluated using comet assay along with micronucleus assay. Moreover, the gene expression of DNA damage response gene (OGG1) was measured by qRT-PCR, after extraction of RNA from the MDBK cell line using the TRIzol method and its conversion to cDNA by reverse-transcriptase PCR. During the experiment, cell viability percentage was measured at different doses of IVM i.e., 25%, 50%, 75%, along with LC50/2, LC50 and LC50*2. It was observed that the gene expression of OGG1 increased as the concentration of IVM increased. It was concluded that IVM has both cytotoxic and genotoxic effects on the MDBK cell line. Furthermore, it is recommended that studies related to the toxic effects of IVM at molecular level and on other model organisms should be conducted to combat its hazardous effects.

Uptake and Biotransformation of Guvermectin in Three Crops after In Vivo and In Vitro Exposure.

Guvermectin, as a novel nucleoside-like biopesticide, could increase the rice yield excellently, but the potential environmental behaviors remain unclear, which pose potential health risks. Therefore, the uptake and biotransformation of guvermectin in three types of crops (rice, lettuce, and carrot) were first evaluated with a hydroponic system. Guvermectin could be rapidly absorbed and reached equilibrium in roots (12-36 h) and shoots (24-60 h) in three plants, and guvermectin was also vulnerable to dissipation in roots (t1/2 1.02-3.65 h) and shoots (t1/2 9.30-17.91 h). In addition, 8 phase I and 2 phase II metabolites, transformed from guvermectin degradation in vivo and in vitro exposure, were identified, and one was confirmed as psicofuranine, which had antibacterial and antitumor properties; other metabolites were nucleoside-like chemicals. Molecular simulation and quantitative polymerase chain reaction further demonstrated that guvermectin was metabolized by the catabolism pathway of an endogenous nucleotide. Guvermectin had similar metabolites in three plants, but the biotransformation ability had a strong species dependence. In addition, all the metabolites exhibit neglectable toxicities (bioconcentration factor <2000 L/kg b.w., LC50,rat > 5000 mg/kg b.w.) by prediction. The study provided valuable evidence for the application of guvermectin and a better understanding of the biological behavior of nucleoside-like pesticides.

Functional Analysis of Insecticide Inhibition and Metabolism of Six Glutathione S-Transferases in the Rice Stem Borer, Chilo suppressalis.

The glutathione S-transferases (GSTs) are important detoxifying enzymes in insects. Our previous studies found that the susceptibility of Chilo suppressalis to abamectin was significantly increased when the CsGST activity was inhibited by glutathione (GSH) depletory. In this study, the potential detoxification mechanisms of CsGSTs to abamectin were explored. Six CsGSTs of C. suppressalis were expressed in vitro. Enzymatic kinetic parameters including Km and Vmax of recombinant CsGSTs were determined, and results showed that all of the six CsGSTs were catalytically active and displaying glutathione transferase activity. Insecticide inhibitions revealed that a low concentration of abamectin could effectively inhibit the activities of CsGSTs including CsGSTd1, CsGSTe4, CsGSTo2, CsGSTs3, and CsGSTu1. However, the in vitro metabolism assay found that the six CsGSTs could not metabolize abamectin directly. Additionally, the glutathione transferase activity of CsGSTs in C. suppressalis was significantly increased post-treatment with abamectin. Comprehensive analysis of the results in present and our previous studies demonstrated that CsGSTs play an important role in detoxification of abamectin by catalyzing the conjugation of GSH to abamectin in C. suppressalis, and the high binding affinities of CsGSTd1, CsGSTe4, CsGSTo2, CsGSTs3, and CsGSTu1 with abamectin might also suggest the involvement of CsGSTs in detoxification of abamectin via the noncatalytic passive binding and sequestration instead of direct metabolism. These studies are helpful to better understand the detoxification mechanisms of GSTs in insects.

Ivermectin resistance mechanisms in ectoparasites: a scoping review.

Ivermectin mass drug administration has been used for decades to target human and veterinary ectoparasites, and is currently being considered for use against malaria vectors. Although there have been few reports of resistance to date in human ectoparasites, we must anticipate the development of resistance in mosquitoes in the future. Hence, through this review, we mapped the existing evidence on ivermectin resistance mechanisms in human ectoparasites. A search was conducted on the 8th November 2023 through databases, PubMed, Web of Science, and Google Scholar, using terms related to ivermectin, human and veterinary ectoparasites, and resistance. Abstracts (5893) were screened by JFA and CK. Data on the study organism, the type of resistance, the analysis methods, and, where applicable, the gene loci of interest were extracted from the studies. Details of the methodology and results of each study were summarised narratively and in a table. Eighteen studies were identified describing ivermectin resistance in ectoparasites. Two studies described target site resistance; and 16 studies reported metabolic resistance and/or changes in efflux pump expression. The studies investigated genetic mutations in resistant organisms, detoxification, and efflux pump expression in resistant versus susceptible organisms, and the effect of synergists on mortality or detoxification enzyme/efflux pump transcription. To date, very few studies have been conducted examining the mechanisms of ivermectin resistance in ectoparasites, with only two on Anopheles spp. Of the existing studies, most examined detoxification and efflux pump gene expression, and only two studies in lice investigated target-site resistance. Further research in this field should be encouraged, to allow for close monitoring in ivermectin MDA programmes, and the development of resistance mitigation strategies.