24-h Exposure Research Articles

Rhizoglyphus robini, a pest mite of saffron, is unable to resist extracellular ice formation.

The saffron mite, Rhizoglyphus robini Claparède (Acari, Astigmata: Acaridae), is one of the most important pests of saffron-producing regions in Iran. It causes yellowing and decreases saffron growth, and finally it destroys the bulbs. In this research, the cold tolerance and supercooling point (SCP) of the saffron mite were measured in three populations and two temperature regimes. Our results showed that the mean SCP of the saffron mite was approximately -14.6°C without significant difference among the populations. On the contrary, acclimation of the mites significantly decreased their SCP to a mean of approximately -16.5°C. Exposure of the mites for 24h to 0 and -2.5°C had no significant effect on the survival of the mites but when the mites were exposed to -5.0°C for 24h, survival of the three populations reached the lowest level of roughly 60%. By 24-h exposure to -7.5°C, survival of the mites was almost negligible. As a large proportion of mortality was observed above the SCP, and LT50 > SCP, it can be inferred that the saffron mite is likely a chill-susceptible species. This suggests that the saffron mite lacks the ability to withstand extracellular ice formation. Overall, the results of the current study suggest no significant physiological differences between populations of the saffron mite.

Drug permeation enhancement, efficacy, and safety assessment of azelaic acid loaded SNEDDS hydrogel to overcome the treatment barriers of atopic dermatitis

Atopic dermatitis is one of the most widespread chronic inflammatory skin conditions that can occur at any age, though the prevalence is highest in children. The purpose of the current study was to prepare and optimize the azelaic acid (AzA) loaded SNEDDS using Pseudo ternary phase diagram, which was subsequently incorporated into the Carbopol 940 hydrogel for the treatment of atopic dermatitis. The composition was evaluated for size, entrapment efficiency, in vitro, ex vivo, and in vivo studies. The polydispersity index of the optimized preparation was found to be less than 0.5, and the size of the distributed globules was found to be 151.20 ± 3.67 nm. The SNEDDS hydrogel was characterized for pH, viscosity, spreadability, and texture analysis. When compared to the marketed formulation, SNEDDS hydrogel was found to have a higher rate of permeation through the rat skin. In addition, a skin irritation test carried out on experimental animals showed that the SNEDDS formulation did not exhibit any erythematous symptoms after a 24-h exposure. In conclusion, the topical delivery of AzA through the skin using SNEDDS hydrogel could prove to be an effective approach for the treatment of atopic dermatitis.

Photonitration of pyrene adsorbed on silica gel with NO2

To examine the heterogeneous photonitration of pyrene with NO2 (approximately 0.2 ppm) on a heavy-traffic road, we studied the photonitration of pyrene adsorbed (pyreneads) on silica gel, which was used as SiO2 in particulate matter (PM), with NO2 (10.2, 2.0, and 0.20 ppm) under the atmospheric concentration ratio of pyreneads to NO2 and compared the results with those obtained in the dark. The effects of irradiation, wavelength, and oxygen concentration in a NO2 diluent on the photonitration were examined using a fluidized-bed column irradiated with simulated or real sunlight. Under the UV-light absorption of pyrene, the concentration of pyrene decreased exponentially in accordance with a pseudo-first-order reaction, while in the dark, it decreased sigmoidally in accordance with a H+-autocatalyzed reaction. The distribution and the yields of formed nitration products and their photooxidation products were affected by the light intensity, concentrations of NO2, and oxygen in the NO2 diluent. In the photonitration experiments using a high-pressure mercury lamp, formed 1-nitropyrene and minor dinitropyrenes were decreased by the transformation into their photooxidation products. Under 8-h exposure of pyrene to 10.2-ppm NO2, the yield of 1-nitropyrene was 42% in N2 and 28% in air. The oxygen inhibitory effect can be explained by the energy transfer from 1pyrene* to oxygen. Radical cation intermediate (pyrene•+-NO2−) was proposed for 1-nitropyrene formation. Under 24-h exposure of pyrene to 2.0-ppm NO2, the yields of 1-nitropyrene and the photooxidation products were 21.6% and 8.0%, respectively, in N2 and 4.9% and 3.8%, respectively, in air. Under 24-h exposure of pyrene to 0.20-ppm NO2, which is two times the 1-h NO2 standard in the USA and China, the yields of 1-nitropyrene and the photooxidation products were 2.3% and 3.4%, respectively, in N2 and 2.1% and 0.9%, respectively, in air. The significant decrease in the yields of 1-nitropyrene and the photooxidation products under the concentration of 0.20-ppm NO2 can be explained by their easy photodecomposition with the increase in the photolysis of pyrene. Under the concentration of 0.20-ppm NO2 in air, which is approximately the concentration on heavy-traffic roads, the decay rate of pyrene by the photonitration was increased by own photolysis, although the photonitration was inhibited by oxygen in air.

Disparities in Cisplatin-Induced Cytotoxicity-A Meta-Analysis of Selected Cancer Cell Lines.

Cisplatin is a classic anticancer drug widely used as a reference drug to test new metal complex drug candidates. We found an unexpected diversity in cisplatin-related cytotoxicity values, expressed as IC50 (the half-maximal inhibitory concentration) in tumour cell lines, such as MCF-7, HepG2 and HeLa. We reviewed the data published from 2018 to 2022. A total of 41 articles based on 56 in vitro experiments met our eligibility criteria. Using a meta-analysis based on a random effect model, we evaluated the cytotoxicity of cisplatin (IC50) after 48- or 72-h cell exposure. We found large differences between studies using a particular cell line. According to the random effect model, the 95% confidence intervals for IC50 were extremely wide. The heterogeneity of cisplatin IC50, as measured by the I2 index for all cancer cell lines, was over 99.7% at culture times of 48 or 72 h. Therefore, the variability between studies is due to experimental heterogeneity rather than chance. Despite the higher IC50 values after 48 h than after 72 h, the heterogeneity between the two culture periods did not differ significantly. This indicates that the duration of cultivation is not the main cause of heterogeneity. Therefore, the available data is diverse and not useful as a reference. We discuss possible reasons for the IC50 heterogeneity and advise researchers to conduct preliminary testing before starting experiments and not to solely rely on the published data. We hope that this systematic meta-analysis will provide valuable information for researchers searching for new cancer drugs using cisplatin as a reference drug.

Effects of Manganese and Iron, Alone or in Combination, on Apoptosis in BV2 Cells.

The aim of study was to address the effects of manganese and iron, alone and in combination, on apoptosis of BV2 microglia cells, and to determine if combined exposure to these metals augments their individual toxicity. We used a murine microglial BV2 cell line. Cell cytotoxicity was analyzed by propidium iodide (PI) exclusion assay. Cell ROS production was analyzed by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) probe staining. Pro-inflammatory cytokine production was monitored by ELISA. Cell apoptosis was analyzed by PE Annexin V/7-AAD staining. Mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting to analyze the effect of manganese, iron alone, or their combined exposure on the activation of caspase9, P53, Bax, and Bcl2 apoptosis signaling pathways. Caspase3 activity was determined using a Colorimetric. Manganese, iron, and their combined exposure for 24h induced the activation of BV2 microglia cells and increased ROS production and the expression of the inflammatory cytokines, IL-1β and TNF-α. And we also found that the apoptosis rate increased, mitochondrial membrane potential decreased, apoptosis-related proteins caspase9, P53, Bax, and Bcl2 expression increased, and caspase3 activity increased. Furthermore, we found that combined manganese-iron cytotoxicity was lower than that induced by manganese exposure alone. Manganese, iron alone, or their combination exposure can induce apoptosis in glial cells. Iron can reduce the toxicity of manganese, and there is an antagonistic effect between manganese and iron.

Antidepressants escitalopram and venlafaxine up-regulate BDNF promoter IV but down-regulate neurite outgrowth in differentiating SH-SY5Y neurons

Antidepressants are used to treat depression and some anxiety disorders, including use in pregnant patients. The pharmacological actions of these drugs generally determine the uptake and metabolism of a series of neurotransmitters, such as serotonin, norepinephrine, or dopamine, along with an increase in BDNF expression. However, many aspects of antidepressant action remain unknown, particularly whether antidepressants interfere with normal neurodevelopment when taken by pregnant women. In order to reveal cellular and molecular implications crucial to the functioning of pathways related to antidepressant effects, we performed an investigation on neuronally differentiating human SH-SY5Y cells. To our knowledge, this is the first time human SH-SY5Y cells in cultures of purely neuronal cells induced by controlled differentiation with retinoic acid are followed by short-term 48-h exposure to 0.1–10 μM escitalopram or venlafaxine. Treatment with antidepressants (1 μM) did not affect the electrophysiological properties of SH-SY5Y cells. However, the percentage of mature neurons exhibiting voltage-gated sodium currents was substantially higher in cultures pre-treated with either antidepressant. After exposure to escitalopram or venlafaxine, we observed a concentration-dependent increase in activity-dependent BDNF promoter IV activation. The assessment of neurite metrics showed significant down-regulation of neurite outgrowth upon exposure to venlafaxine. Identified changes may represent links to molecular processes of importance to depression and be involved in neurodevelopmental alterations observed in postpartum children exposed to antidepressants antenatally.

Green synthesis of ZnO-NPs using endophytic fungal extract of Xylaria arbuscula from Blumea axillaris and its biological applications

The biogenic manufacture of nanoparticles utilising endophytic fungus is an eco-friendly, cost-effective, and secure alternative to constructing chemical methods. The prime focus of the study was to fabricate ZnONPs using the biomass filtrate of endophytic Xylaria arbuscula isolated from Blumea axillaris Linn. and to evaluate their biological properties. The characterisation of the biosynthesized ZnO-NPs was done utilising both spectroscopic and microscopic methods. The bioinspired NPs showed a surface plasmon peak at 370 nm; SEM and TEM micrographs illustrated the hexagonal organisation; XRD spectra proved the crystalline phase as hexagonal wurtzite; EDX analysis confirmed the presence of zinc and oxygen atoms; and the zeta potential analysis proved the stability of ZnONPs. In addition, they also demonstrated significant concentration-dependent inhibition of antimicrobial, antioxidant, anti-inflammatory, and antidiabetic potential in comparison with the reference drugs. In vitro cytotoxicity and wound healing potential of ZnONPs were examined in L929 cell lines, illustrating that they accelerated the wound healing process by roughly 95.37 ± 1.12% after a 24-h exposure to ZnONPs. The photocatalytic activity of the ZnONPs was examined by degrading the methylene blue dye under solar irradiation. In conclusion, our outcomes showed that mycosynthesized ZnONPs possessed potent bioactivity and could be an excellent choice for biomedical applications.

Sulfuryl fluoride fumigation to eliminate all life stages of Araecerus fasciculatus (Coleoptera: Anthribidae)

Araecerus fasciculatus (De Geer) is one of the insect pests that often infests agricultural commodities in storage. This study aimed to determine the effectiveness of sulfuryl fluoride against all life stages of A. fasciculatus. In the preliminary test, sulfuryl fluoride was applied at doses of 0, 12, 24, 36, 48, 60, and 72 g/m3 and 24 and 48 h exposure times. Two hundred insects were used for each treatment. After being treated with sulfuryl fluoride, the characteristics of A. fasciculatus eggs were observed histopathologically. Further testing was carried out on the most tolerant stadium using 10,000 insects. The results of the preliminary test showed that at 24 h of exposure, the mortality of the adult, larva, and pupa stages reached 100% at the application doses of 12, 36, and 60 g/m3, respectively, while the mortality of the egg stage did not reach 100% at a 24-h exposure time at a dose of 12–72 g/m3. The egg stage mortality reached 100% when the application dose was 60 g/m3 and the exposure time was 48 h. Further test against the most tolerant stage (eggs) showed that none of the treated A. fasciculatus eggs reached the adult stage after being exposed to sulfuryl fluoride at a dose of 60 g/m3 and an exposure time of 48 h.

Acute turbidity exposures with Port of Miami sediments impact Orbicella faveolata tissue regeneration

We evaluated acute turbidity effects on a threatened coral species (Orbicella faveolata) under three short-term challenge scenarios using a Port of Miami sediment homogenate to simulate turbid conditions during dredging. For these experiments we designed a simple coral challenge test system that kept turbidity stable, without adverse effects to the coral. A 96-h coral challenge experiment demonstrated that low turbidity levels (≥4 NTU) have negative effects on O. faveolata tissue regeneration. A 48-h turbidity exposure (maximum 30 NTU) had no effect on O. faveolata tissue regeneration, showing that short term turbidity exposures may not be detrimental to coral health. In a 13-day test, treated coral fragments (maximum 30 NTU) exhibited significant delays in tissue regeneration, but recovery was observed after approximately one week. The results presented here can be used to inform management decisions for proposed dredging activities proximal to coral reef habitats.

Sublethal effects of thiamethoxam on immune system cells in the workers of Bombus terrestris (Hymenoptera: Apidae).

Neonicotinoids harm especially bumblebees and other species in agricultural areas all over the world. The toxic effect of thiamethoxam from the neonicotinoid group has been little studied especially on bees. This research aimed to evaluate the effects of thiamethoxam on the immune system cells of Bombus terrestris workers. Different ratios of 1/1000, 1/100 and 1/10 of the recommended maximum application dose of thiamethoxam formed the experimental groups. Ten foraging workers were used for each dose and control groups. Contamination was ensured by spraying the prepared suspensions at different ratios to the bees for 20s at a pressure of 1atm. The effects of thiamethoxam on the structures of immune system cells of bumblebees and the amount of these cells were investigated after 48h of exposure. In general, anomalies such as vacuolization, cell membrane irregularities and cell shape changes were detected in prohemocyte, plasmatocyte, granulocyte, spherulocyte and oenocytoid in each dose group. Hemocyte area measurements in all groups were examined comparatively between groups. In general, granulocyte and plasmatocyte sizes were decreased, while spherulocyte and oenocytoid were increased. It was also determined that there was a significant decrease in the amount of hemocytes in the 1 mm3 hemolymph as dose increased. The results of the study revealed that sublethal doses of thiamethoxam negatively affected hemocytes and their amounts of B. terrestris workers.

Tradescantia-Based Test Systems Can Be Used for the Evaluation of the Toxic Potential of Harmful Algal Blooms

Harmful algal blooms (HABs) are overgrowths of toxic strains of algae (diatoms, green) and cyanobacteria (blue-green algae). While occurring naturally, human-induced environmental changes have resulted in more frequent occurrences of such blooms worldwide. Meantime, the ecotoxicological risk of HABs is rarely evaluated by means of standard test methods. For the first time, the genotoxic potential of the HAB event 2020 was assessed using two different Tradescantia-based test systems (Trad-SHM and Trad-MN, 24-h exposure). An integrated analysis of biological (algal abundance) and ecotoxicological (testing) data revealed linkages among algal proliferation, changes in Tradescantia stamen hairs (mutations and suppressed growth) and chromosomal aberrations during microsporogenesis (appearance of micronuclei) that were likely to be caused by toxic algal groups. Green alga Botryococcus braunii and the cyanobacterial species Anabaena and Oscillatoria could suppress stamen hair growth; Cyanobacteria Phormidium and Aphanothece sp. could trigger mutations in stamen hairs (appearance of pink and colorless cells); and Oscillatoria sp. could be responsible for the occurrence of chromosomal damage. Diatom proliferation in the spring was not related to the genotoxic response in Tradescantia. Both tests, the Trad-SHM and Trad-MN, are suitable for the evaluation of the toxic potential of HABs.

Small change, big difference: A promising praziquantel derivative designated P96 with broad-spectrum antischistosomal activity for chemotherapy of schistosomiasis japonica.

Praziquantel (PZQ) has been the first line antischistosomal drug for all species of Schistosoma, and the only available drug for schistosomiasis japonica, without any alternative drugs since the 1980s. However, PZQ cannot prevent reinfection, and cannot cure schistosomiasis thoroughly because of its poor activity against juvenile schistosomes. In addition, reliance on a single drug is extremely dangerous, the development and spread of resistance to PZQ is becoming a great concern. Therefore, development of novel drug candidates for treatment and control of schistosomiasis is urgently needed. One of the PZQ derivative christened P96 with the substitution of cyclohexyl by cyclopentyl was synthesized by School of Pharmaceutical Sciences of Shandong University. We investigated the in vitro and in vivo activities of P96 against different developmental stages of S. japonicum. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of P96 in vitro. Both mouse and rabbit models were employed to evaluate schistosomicidal efficacy of P96 in vivo. Besides calculation of worm reduction rate and egg reduction rate, quantitative real-time PCR was used to evaluate the in vivo antischistosomal activity of P96 at molecular level. In vitro, after 24h exposure, P96 demonstrated the highest activities against both juvenile and adult worm of S. japonicum in comparison to PZQ. The antischistosomal efficacy was concentration-dependent, with P96 at 50μM demonstrating the most evident schistosomicidal effect. Scanning electron microscopy demonstrated that P96 caused more severe damages to schistosomula and adult worm tegument compared to PZQ. In vivo, our results showed that P96 was effective against S. japonicum at all developmental stages. Notably, its efficacy against young stage worms was significantly improved compared to PZQ. Moreover, P96 retained the high activity comparable to PZQ against the adult worm of S. japonicum. P96 is a promising drug candidate for chemotherapy of schistosomiasis japonica, which has broad spectrum of action against various developmental stage, potentially addressing the deficiency of PZQ. It might be promoted as a drug candidate for use either alone or in combination with PZQ for the treatment of schistosomiasis.

Mapping Aedes aegypti indoor resting behavior reveals a preference vulnerable to householder-led vector control.

Many mosquito vectors rest inside human habitations, a behavioral trait that is exploited for vector control by indoor residual spraying (IRS) of interior walls with insecticide. Although IRS and its refined version targeted IRS are very effective against Aedes aegypti, they are expensive and logistically challenging to deliver in densely populated urban areas where outbreaks of dengue and other arboviruses are the greatest challenge. In experiments in Recife, Brazil, we set out to quantify the indoor resting behavior of Ae. aegypti at a level beyond that previously reported. We found that significantly more Ae. aegypti males, unfed and fed females visited the base of walls (height 0-20 cm, corresponding to 12.3% of the total wall surface) more frequently than upper wall areas, with the difference more pronounced at higher temperatures. When the lowest 20 cm of the walls was treated with an appropriate insecticide and colored black, we recorded up to 85% cumulative mortality after 24-h exposure in the experimental room. The findings are significant because feasibly, householders could treat this small and accessible target zone manually, without the need for visits by costly IRS teams or equipment, reducing insecticide use and enabling communities to actively protect their own indoor environment.

Cytotoxicity and genotoxicity of tributyltin in the early embryonic chick, Gallus gallus domesticus.

Tributyltin (TBT) is used in many commercial applications, including pesticides and antifouling paints, due to its biocidal properties. We examined the cytotoxicity and genotoxicity of TBT in the early chick embryo (Gallus gallus domesticus). Chick embryos (11 days) were treated with various doses of TBT to measure LD50 values for 24, 48, and 72h exposures, which were determined to be 110, 54, and 18μg/egg, respectively. The embryos were exposed to sub-lethal doses of TBT for evaluation of cytotoxicity and genotoxicity. An increase in the incidence of micronuclei (MN) was observed but it was not statistically significant. Induction of other nuclear abnormalities (ONA) after 72h TBT exposure was significant. A significant increase in comet assay tail DNA content was also detected in TBT-exposed embryos. Cytotoxicity was also evidenced by alteration in the polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) ratio and by an increase in the erythroblast population in treated organisms. The cytotoxicity and genotoxicity of TBT may have long-term complications in later stages of the life cycle.

Repellent effect of Gardenia jasminoides ethanol extracted oil on Blattella germanica and Monomorium pharaonis

Summary The study examined the repellency of Gardenia jasminoides ethanol-extracted oil against the German cockroach, Blattella germanica, and the pharaoh ant, Monomorium pharaonis, which are serious pests in areas of public health hygiene. For the repellency tests, 31.4 μg of the oil was applied per cm2 on one half of filter paper discs (9 or 15 cm diameter for the ant and cockroach, respectively), whereas the other half was treated as control (DMSO + Tween). Repellency effects were observed 1, 2, 3 and 4 h after the insect release. The oil showed high repellency against all life stages of cockroaches and worker ants. The maximum repellency was observed for the cockroach adults (81.7 ± 3.1%) followed by the fourth, third and second nymphal stages (76.7 ± 4.2, 75.0 ± 3.4, and 56.7 ± 8.4%, respectively), after 1h exposure. The repellence effect was strong against worker ants (78.3 ± 4.8%) after 1 h exposure. The repellence effect can last at least four hours for both species. Analysis of Gardenia oil with Gas chromatography-mass spectrometry identified 14 major chemical components.

Bioactivity of Clitoria ternatea Crude Extracts Against Pathogenic Bacteria

Clitoria ternatea, sometimes referred to as the Asian pigeon wings blue pea, the butterfly pea, or the Darwin pea, is a Fabaceae plant species that has been shown to possess antibacterial effects against several pathogenic microbes. Hence, the present study has been carried out to access the antibacterial activity of C. ternatea flower extracted with water and methanol against pathogenic bacteria. The well and disk diffusion assays were performed to determine the antibacterial activity of C. ternatea flower extracts. The efficacy of the extracts was then evaluated via broth microdilution assay to obtain MIC and MBC values and the growth reduction assay. Meanwhile, the DPPH scavenging test was used to assess the antioxidant activity of the crude extracts. The results of the well and disc diffusion assays showed that Gram-positive bacteria were more sensitive to both extracts compared to Gram-negative bacteria. Meanwhile, the methanolic extract showed higher antibacterial activity on both Gram-positive and Gram-negative bacteria compared to the aqueous extract. The results of the MIC and MBC tests showed that the methanolic extract was bactericidal to both Gram-positive and Gram-negative bacteria. The aqueous extract, however, demonstrated bacteriostatic activity against Gram-negative bacteria and bactericidal activity solely against Gram-positive bacteria. After a 24-h exposure period, a growth reduction assay showed that the methanolic extract could suppress both Gram-positive and Gram-negative bacteria by up to 99%. Meanwhile, the aqueous extract showed an inhibition percentage value ranging from 75% to 96% after an incubation period. The aqueous extract had the lowest antioxidant activity, with an EC50 value of 87.78 µg/mL, whereas the methanolic extract had a fair amount of antioxidant activity when compared to the control (quercetin), according to the DPPH scavenging assay. The present study suggests that C. ternatea extracts as a potential antibacterial agent against pathogenic bacteria with significant antioxidant activity and this activity may be due to the presence of anthocyanin and its derivatives.

Pre-exposure to seawater or chloride salts influences the avoidance-selection behavior of zebrafish larvae in a conductivity gradient

The risk assessment of freshwater salinization is constructed around standard assays and using sodium chloride (NaCl), neglecting that the stressor is most likely a complex mixture of ions and the possibility of prior contact with it, triggering acclimation mechanisms in the freshwater biota. To date, as far as we are aware of, no information has been generated integrating both acclimation and avoidance behavior in the context of salinization, that may allow these risk assessments upgrading. Accordingly, 6-days-old Danio rerio larvae were selected to perform 12-h avoidance assays in a non-confined 6-compartment linear system to simulate conductivity gradients using seawater (SW) and the chloride salts MgCl2, KCl, and CaCl2. Salinity gradients were established from conductivities known to cause 50% egg mortality in a 96-h exposure (LC50,96h,embryo). The triggering of acclimation processes, which could influence organisms’ avoidance-selection under the conductivity gradients, was also studied using larvae pre-exposed to lethal levels of each salt or SW. Median avoidance conductivities after a 12-h of exposure (AC50,12h), and the Population Immediate Decline (PID) were computed.All non-pre-exposed larvae were able to detect and flee from conductivities corresponding to the LC50,96h,embryo, selecting compartments with lower conductivities, except for KCl. The AC50,12h and LC50,96h overlapped for MgCl2 and CaCl2, though the former is considered as more sensitive as it was obtained in 12 h of exposure. The AC50,12h for SW was 1.83-fold lower than the LC50,96h, thus, reinforcing the higher sensitivity of the parameter ACx and its adequacy for risk assessment frameworks. The PID, at low conductivities, was solely explained by the avoidance behavior of non-pre-exposed larvae. Larvae pre-exposed to lethal levels of salt or SW were found to select higher conductivities, except for MgCl2. Results indicated that avoidance-selection assays are ecologically relevant and sensitive tools to be used in risk assessment processes. Stressor pre-exposure influenced organisms’ avoidance-selection behavior under conductivity gradients, suggesting that under salinization events organisms may acclimate, remaining in altered habitats.

Sublethal effects of spinetoram and emamectin benzoate on key demographic parameters of fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae) under laboratory conditions.

Fall armyworm (FAW) Spodoptera frugiperda, is a serious invasive pest of many crops that causes huge economic losses to agricultural commodities. Insecticides are employed for the management of S. frugiperda. In this study, we investigated the impact of sublethal concentration (LC10) and low lethal concentration (LC30) of spinetoram and emamectin benzoate on S. frugiperda using two-sex life table method. Bioassay results revealed that emamectin benzoate exhibited more toxicity on the 3rd instar of S. frugiperda (LC50 8.35 × 10-4mgL-1) than spinetoram (LC50 2.6 × 10-2mgL-1) after 48h exposure. The total longevity, adult pre-ovipositional period (APOP) and total pre-ovipositional period (TPOP) were prolonged, while pre-adult survival rate and fecundity were reduced at both concentrations of spinetoram and emamectin benzoate. Moreover, the key demographic parameters, including the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0), were significantly lower in insecticide treated groups as compared to untreated insects. Our findings revealed that the sublethal and low lethal concentrations of both insecticides reduce the survival and reproductive capability of S. frugiperda. These results would be useful to assess the overall effect of both insecticides on S. frugiperda and can provide important implications for the rational utilization of insecticides against S. frugiperda.

26-OR: A Novel Drug That Normalizes Hyperglycemia in Type 1 Diabetes

Treatment of hyperglycemia in patients with type 1 diabetes (T1D) depends on insulin injections, which risk hypoglycemia and represent an unfavorable route of administration. Inhibition of EphA4 signaling in α-cells reduces glucagon hypersecretion, which suggests an alternative approach for the treatment of hyperglycemia in T1D. We have designed and synthesized a novel EphA4 agonist (Ki = 0.1 µM), termed WCDD301, that dose-dependently suppresses glucagon secretion (p<0.001) from mouse islets and dispersed α-cells at high glucose levels. Co-treatment of the EphA4 competitive inhibitor, Rhyncophylline (2.5µM) and WCDD301 (2.5µM or 5µM) substantially or partially, respectively, abolishes WCDD301 effects. Further, WCDD301 reduces glucagon secretion from nondiabetic human donor islet cells following 1h (p<0.05), 3h (p<0.01) and 6h (p<0.001) exposure. WCDD301 suppresses glucagon secretion (p<0.001) from isolated islets and dispersed islet cells from T1D subjects, comparable to the natural EphA4 ligand ephrinA5. Similar to ephrinA5 treatment, WCDD301 increases F-actin density in both human and mouse α-cells. WCDD301 exhibits good plasma (>289 and 105 min) and microsomal (>145 and 93.6 min) stability in human and mouse, respectively. In STZ-induced diabetic mice (initial blood glucose <300mg/dL, n=6), oral administration of WCDD301 (daily 10 mg/kg) substantially reduces blood glucose levels (140±31 mg/dL after four weeks). In diabetic NOD mice (initial blood glucose 249.6±13.1 mg/dL; n=7), oral administration of WCDD301 (daily 10 mg/kg) normalizes glucose (105±2.6 mg/dL after 3 weeks), which remains constant for >3 months (experiments on-going) accompanied by reduced plasma glucagon (16.6±7.9 pg/mL) compared to diabetic control (328.5±18.7 pg/ml). The data support our hypothesis that oral administration of WCDD301 suppresses glucagon secretion by an EphA4-dependent pathway. The recovery of euglycemia in T1D mouse models is promising for further evaluation towards potential treatment of T1D. Disclosure F. Asadi: None. S.C. Gunawardana: None. D.W. Piston: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust (2305-06050); National Institutes of Health (R01DK123301, P30DK020579)

Exposure to Alexandrium spp. impairs the development of Green-lipped mussel (Perna canaliculus) embryos and larvae

The green-lipped mussel (GLM) Perna canaliculus is an economically, ecologically, and culturally important species in Aotearoa New Zealand. Since 2011, harmful algal blooms (HABs) of Alexandrium spp. have occurred annually in the Marlborough Sounds, the largest GLM aquaculture region in New Zealand. Across a similar timeframe, there has been a severe reduction in wild spat (juvenile mussel) catch. This research investigated the effects of Alexandrium pacificum (which produces paralytic shellfish toxins; PSTs) and A. minutum (a non-producer of PSTs) on the development of four GLM larval life stages (gametes, embryos, D-stage and settlement).Early life stages of GLM were exposed to environmentally relevant concentrations of Alexandrium spp. as whole cell, lysate and filtrate treatments. A 48-h exposure of embryos to whole A. pacificum cells at 500 cells mL−1 caused lysis of embryos, severe abnormalities, and reduced development through to veliger (D-stage) larvae by 85%. GLM growth was impaired at cell concentrations as low as 250 cells mL−1 during a 4-day exposure of D-stage larvae to both Alexandrium spp. Exposure of GLM to both whole and lysed treatments of Alexandrium spp. at 500 cells mL−1 resulted in halved larval growth rates (2.00 µm day−1 vs 4.48 µm day−1 in the control) and growth remained impeded during a 4-day recovery period.Both A. pacificum and A. minutum were found to negatively impact D-larvae. Both whole-cell and lysed-cell treatments of A. pacificum had similar negative effects, suggesting that Alexandrium spp. toxicity to D-larvae is independent of PSTs. Additionally, cell membrane-free treatments of A. pacificum had no negative effects on embryo development, indicating that cell surface-associated bioactive compounds may be responsible for the observed negative effects during this early life stage.Conversely, non-PST-producing A. minutum was toxic to D-stage larvae but not to embryos; larval growth was reduced following a brief 1 h exposure of sperm to cell membrane-free treatments of A. pacificum. No effects were recorded in GLM larvae exposed during settlement, highlighting the potential for differences in susceptibility of early life stages to Alexandrium spp. exposure and the influence of exposure durations.In the wild, blooms of Alexandrium spp. can persist for several months, reaching cell densities higher than those investigated in the present study, and as such may be detrimental to the vulnerable early life stages of GLM.