Evaluating the toxicity effects of thiamethoxam and its main metabolite clothianidin to earthworms (Eisenia fetida) from the perspective of endogenous metabolites.

The widespread application of neonicotinoid insecticides (NNIs) has attracted widespread attention to their potential ecotoxicological effects. In this study, we systematically evaluated the toxic effects of thiamethoxam (TMX) and its metabolite clothianidin (CLO) on earthworms (Eisenia fetida). Specifically, the antioxidant system responses and endogenous metabolite metabolism responses in earthworms were analyzed in the temporal dimension after 7, 14, 21 and 28 days of exposure to TMX and CLO. The results found that TMX and CLO could inhibit the growth phenotype of earthworms and cause significant changes in antioxidant system related indicators. More importantly, we found that TMX and CLO could cause significant changes in the metabolic profiles of earthworms through NMR-based metabolomics. From the changes in endogenous metabolites, the toxicity effects of TMX on earthworms gradually increases with prolonged exposure time. Differently, the toxicity effects of CLO on earthworms is significantly higher than that of TMX in the early stages of exposure. Meanwhile, these impacts will not weaken with prolonged exposure time. Furthermore, the results of KEGG enrichment pathway analysis indicated that TMX and CLO could significantly interfere with energy homeostasis, redox homeostasis, osmotic regulation, amino acid metabolism and protein synthesis in earthworms. These findings further deepen our understanding of the ecotoxicological effects of NNIs on soil organism.

Fabrication of thermo-responsive microcapsule pesticide delivery system from maleic anhydride-functionalized cellulose nanocrystals-stabilized pickering emulsion template.

The overuse of pesticides has shown their malpractices. Novel and sustainable formulations have consequently attracted abundant attention but still appear to have drawbacks. Here, we use a maleic anhydride-functionalized cellulose nanocrystals-stabilized Pickering emulsions template to prepare thermo-responsive microcapsules for a pesticide delivery system via radical polymerization with N-isopropyl acrylamide. The microcapsules (MACNCs-g-NIPAM) are characterized by the microscope, SEM, FTIR, XRD, TG-DTG, and DSC techniques. Imidacloprid (IMI) is loaded on MACNCs-g-NIPAM to form smart release systems (IMI@MACNCs-g-NIPAM) with high encapsulation efficiency (~88.49%) and loading capability (~55.02%). The IMI@MACNCs-g-NIPAM present a significant thermo-responsiveness by comparing the release ratios at 35°C and 25°C (76.22% vs 50.78%). It also exhibits advantages in spreadability, retention and flush resistance on the leaf surface compared with the commercial IMI water-dispersible granules (CG). IMI@MACNCs-g-NIPAM also manifest a significant advantage over CG (11.12 mg/L vs 38.90 mg/L for LC50) regarding activity tests of targeted organisms. In addition, IMI@MACNCs-g-NIPAM has shown excellent biocompatibility and low toxicity. All the benefits mentioned above prove the excellent potential of IMI@MACNCs-g-NIPAM as a smart pesticide formulation.

CYP4CE1 Metabolized Nitenpyram through Two Types of Oxidation Reaction, Hydroxylation, and N-Demethylation.

Nitenpyram, taking the place of imidacloprid, is a widely used neonicotinoid insecticide to control Nilaparvata lugens in Asia. Two P450s, CYP4CE1 and CYP6ER1, are key factors in the metabolic resistance against nitenpyram and imidacloprid. In this study, we found that CYP4CE1 expression was strongly associated with nitenpyram resistance in 8 field-collected populations, whereas CYP6ER1 expression correlated with imidacloprid resistance. Hence, we focused on nitenpyram metabolism by CYP4CE1, due to that imidacloprid metabolism by CYP6ER1 has intensively investigated. Mass spectrometry analysis revealed that recombinant CYP4CE1 metabolized nitenpyram into three products, N-desmethyl nitenpyram, hydroxy-nitenpyram, and N-desmethyl hydroxy-nitenpyram, with a preference for hydroxylation. In contrast, CYP6ER1 metabolized nitenpyram into a single product, N-desmethyl nitenpyram. These results provide new insights into the specific catalytic mechanisms of P450 enzymes in neonicotinoid metabolism and underscore the importance of different catalytic reactions in neonicotinoid insecticide resistance.

Sorption and degradation processes of imidacloprid in Florida soils.

Imidacloprid (IDP) is an active ingredient of the Admire brand pesticide used to control the vector (Asian citrus psyllid) that transmits the causative organism Candidatus Liberibacter asiaticus (CLas) for citrus greening or huanglongbing disease. Imidacloprid products are applied via soil drench where citrus roots are mostly concentrated which is between 0 and 60 cm depth. These soil depths exhibit different characteristics that may affect IDP leaching beyond the rooting zone. Representative soil samples were collected from Entisols and Ultisols, which are the dominant soil orders under citrus production in central Florida, at 15 cm increments up to 60 cm to estimate and understand the batch sorption, kinetics, equilibria, and degradation of IDP. Results showed that the equilibrium time for IDP at 0-15 cm depth (10 hours) was 2 times faster than at 15-60 cm (20 hours) for the Entisol. Nevertheless, all depths reached equilibrium within 24 hours for the Entisol. The 0-30 cm depth adsorbed 2 times more IDP than the 30-60 cm depth for both soils. Nevertheless, the adsorption coefficient was approximately ≤ 1 mL g-1 for both soils. The half-life of IDP in both soils ranged from 10 to 17 days. The Entisol showed higher adsorption than the Ultisol at both depths, probably due to relatively lower organic carbon (OC) content in the Ultisol compared to the Entisol. Thus, the Ultisol showed high IDP leaching vulnerability compared to the Entisol. Movement of IDP is affected by the amount of OC in the citrus critical zone.

Superresolution imaging of antibiotic-induced structural disruption of bacteria enabled by photochromic glycomicelles.

Bacterial evolution, particularly in hospital settings, is leading to an increase in multidrug resistance. Understanding the basis for this resistance is critical as it can drive discovery of new antibiotics while allowing the clinical use of known antibiotics to be optimized. Here, we report a photoactive chemical probe for superresolution microscopy that allows for the in situ probing of antibiotic-induced structural disruption of bacteria. Conjugation between a spiropyran (SP) and galactose via click chemistry produces an amphiphilic photochromic glycoprobe, which self-assembles into glycomicelles in water. The hydrophobic inner core of the glycomicelles allows encapsulation of antibiotics. Photoirradiation then serves to convert the SP to the corresponding merocyanine (MR) form. This results in micellar disassembly allowing for release of the antibiotic in an on-demand fashion. The glycomicelles of this study adhere selectively to the surface of a Gram-negative bacterium through multivalent sugar-lectin interaction. Antibiotic release from the glycomicelles then induces membrane collapse. This dynamic process can be imaged in situ by superresolution spectroscopy owing to the "fluorescence blinking" of the SP/MR photochromic pair. This research provides a high-precision imaging tool that may be used to visualize how antibiotics disrupt the structural integrity of bacteria in real time.

Physiological and gene expression responses of Protohermes xanthodes (Megaloptera: Corydalidae) larvae to imidacloprid.

Megaloptera larvae are important bioindicator species and potential resource insects. To further cultivate their economic role, their living environment must be examined in more detail. In this study, we analyzed the physiological and biochemical effects of a sublethal dose of imidacloprid, a widely used neonicotinoid insecticide, on the larvae of Protohermes xanthodes. After treatment with imidacloprid, P. xanthodes larvae exhibited clear symptoms of poisoning, including the head curling up toward the ventral surface. Additionally, the activity of acetylcholinesterase was significantly inhibited following exposure. The activities of glutathione S-transferases initially continuously increased but showed a slight decrease after 8 days. Catalase activity initially increased and then decreased following imidacloprid treatment; superoxide dismutase activity fluctuated over time, and peroxidase activity continuously increased. The expression levels of HSP70s genes were evaluated using qRT-PCR. These results indicate that P. xanthodes larvae exhibit a toxic response to imidacloprid exposure, manifested as oxidative stress, as observed through behavioral and physiological indicators.

A tiny sample rapid visual detection technology for imidacloprid resistance in Aphis gossypii by CRISPR/Cas12a.

Insecticide resistance monitoring is essential for guiding chemical pest control and resistance management policies. Currently, rapid and effective technology for monitoring the resistance of tiny insects in the field is absent. Aphis gossypii Glover is a typical tiny insect, and one of the most frequently reported insecticide-resistant pests. In this study, we established a novel CRISPR/Cas12a-based rapid visual detection approach for detecting the V62I and R81T mutations in the ß1 subunit of the nAChR in A. gossypii, to reflect target-site resistance to imidacloprid. Based on the nAChR ß1 subunit gene in A. gossypii, the V62I/R81T-specific RPA primers and crRNAs were designed, and the ratio of 10 µM/2 µM/10 µM for ssDNA/Cas12a/crRNA was selected as the optimal dosage for the CRISPR reaction, ensuring that Cas12a only accurately recognizes imidacloprid-resistance templates. Our data show that the field populations of resistant insects possessing V62I and R81T mutations to imidacloprid can be accurately identified within one hour using the RPA-CRISPR/Cas12a detection approach under visible blue light at 440-460 nm. The protocol for RPA-CRISPR detection necessitates a single less than 2 mm specimen of A. gossypii tissues to perform RPA-CRISPR detection, and the process only requires a container at 37 °C and a portable blue light at 440-460 nm. Our research represents the first application of RPA-CRISPR technology in insecticide resistance detection, offers a new method for the resistance monitoring of A. gossypii or other tiny insects, helps delay the development of resistance to imidacloprid, improves the sustainability of chemical control, and provides theoretical guidance for managing pest resistance.

Imidacloprid affects human cells through mitochondrial dysfunction and oxidative stress.

Given their relatively low persistence and mammalian toxicity, neonicotinoid pesticides have been extensively used worldwide and are omnipresent in the environment. Recent studies have shown that neonicotinoids may pose adverse effects on non-target organisms other than the known neurotoxicity, raising emerging concerns that these insecticides might pose human health risk through additional toxicity pathways. In the present study, the mitochondria function, oxidative stress, DNA damages, and genes transcription levels were examined in the human neuroblastoma SH-SY5Y cells after 48-h exposure to imidacloprid at concentrations from 0.05 to 200 µmol/L. Results showed that imidacloprid induced mitochondrial dysfunction with the degradation of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) levels. In addition, imidacloprid caused oxidative stress by stimulating the generation of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) via the disruption of calcium ion level and mitochondrial function. Ultimately, the oxidative stress continued to produce DNA damage and apoptosis in SH-SY5Y cells at imidacloprid concentrations above 47.6 µmol/L. Among the evaluated endpoints, ATP was the most sensitive, with a median activity concentration of 0.74 µmol/L. The 5 % hazard concentration of imidacloprid was estimated to be 0.69 µmol/L, which can be used as a threshold for human health risk assessment for imidacloprid. Collectively, our results provide an important support for further research on potential toxicity of neonicotinoids related to mitochondrial toxicity in humans.

Fluorometric detection of copper and imidacloprid using nitrogen-doped graphitic carbon dots: A promising method for environmental monitoring.

Pesticides in environmental samples pose significant risks to ecosystems and human health since they require precise and efficient detection methods. Imidacloprid (IMI), a widely used neonicotinoid insecticide, exemplifies these hazards due to its potential toxicity. This study addresses the urgent need for improved monitoring of such contaminants by introducing a novel fluorometric method for detecting IMI using nitrogen-doped graphite carbon dots (N-GCDs). The sensor operates by quenching fluorescence through the interaction of Cu2+ ions with N-GCDs. Subsequently, IMI binds to the imidazole group, chelates with Cu2+, and restores the fluorescence of N-GCDs. This alternating fluorescence behavior allows for the accurate identification of both Cu2+ and IMI. The sensor exhibits linear detection ranges of 20-100 nM for Cu2+ and 10-140 µg/L for IMI, with detection limits of 18 nM and 1.2 µg/L, respectively. The high sensitivity of this sensor enables the detection of real-world samples, which underscores its potential for practical use in environmental monitoring and agricultural safety.

Recent Advances in the Application of Nitro(het)aromatic Compounds for Treating and/or Fluorescent Imaging of Tumor Hypoxia.

This review delves into recent advancements in the field of nitro(het)aromatic bioreductive agents tailored for hypoxic environments. These compounds are designed to exploit the low-oxygen conditions typically found in solid tumors, making them promising candidates for targeted cancer therapies. Initially, this review focused on their role as gene-directed enzyme prodrugs, which are inert until activated by specific enzymes within tumor cells. Upon activation, these prodrugs undergo chemical transformations that convert them into potent cytotoxic agents, selectively targeting cancerous tissue while sparing healthy cells. Additionally, this review discusses recent developments in prodrug conjugates containing nitro(het)aromatic moieties, designed to activate under low-oxygen conditions within tumors. This approach enhances their efficacy and specificity in cancer treatment. Furthermore, this review covers innovative research on using nitro(het)aromatic compounds as fluorescent probes for imaging hypoxic tumors. These probes enable non-invasive visualization of low-oxygen regions within tumors, providing valuable insights for the diagnosis, treatment planning, and monitoring of therapeutic responses. We hope this review will inspire researchers to design and synthesize improved compounds for selective cancer treatment and early diagnostics.

Neonicotinoid Pesticides Affect Developing Neurons in Experimental Mouse Models and in Human Induced Pluripotent Stem Cell (iPSC)-Derived Neural Cultures and Organoids.

Neonicotinoids are synthetic, nicotine-derived insecticides used worldwide to protect crops and domestic animals from pest insects. The reported evidence shows that they are also able to interact with mammalian nicotine receptors (nAChRs), triggering detrimental responses in cultured neurons. Exposure to high neonicotinoid levels during the fetal period induces neurotoxicity in animal models. Considering the persistent exposure to these insecticides and the key role of nAChRs in brain development, their potential neurotoxicity on mammal central nervous system (CNS) needs further investigations. We studied here the neurodevelopmental effects of different generations of neonicotinoids on CNS cells in mouse fetal brain and primary cultures and in neuronal cells and organoids obtained from human induced pluripotent stem cells (iPSC). Neonicotinoids significantly affect neuron viability, with imidacloprid (IMI) inducing relevant alterations in synaptic protein expression, neurofilament structures, and microglia activation in vitro, and in the brain of prenatally exposed mouse fetuses. IMI induces neurotoxic effects also on developing human iPSC-derived neurons and cortical organoids. Collectively, the current findings show that neonicotinoids might induce impairment during neuro/immune-development in mouse and human CNS cells and provide new insights in the characterization of risk for the exposure to this class of pesticides.

Oculomotor nerve palsy caused by imidacloprid at initial diagnosis: A case report.

RATIONALE: Amid the pervasive deployment of imidacloprid, the incidence of poisoning from this compound has risen markedly. Those afflicted with imidacloprid poisoning typically exhibit symptoms ranging from headaches, dizziness, nausea, and abdominal pain, to impaired consciousness and breathlessness, yet instances of ocular paralysis induced by this toxin have not previously been documented. PATIENT CONCERNS: When the pesticide spray inadvertently made contact with the patient's eyes, they were seared with a burning sensation and discomfort. Subsequent to this incident, on the second day, the individual began to experience diplopia in the right eye and found it arduous to elevate his eyelids, indicating a challenge in achieving full extension. DIAGNOSES: Based on the medical history, symptoms, and signs, the patient was diagnosed with oculomotor nerve palsy caused by imidacloprid. INTERVENTIONS: The treatment involved intravenous dexamethasone to reduce inflammatory response in the eye tissue; oral pantoprazole enteric-coated tablets to suppress acid production and protect the stomach; Xuesaitong administered intravenously to improve blood supply to the eye and promote metabolism of toxins; vitamin C, cobamamide, and vitamin B1 for nerve nutrition and antioxidant effects; local application of tobramycin-dexamethasone eye drops for anti-inflammatory purposes; and repeated flushing of the conjunctival sac with saline. Finally, the patient improved and was discharged. OUTCOMES: After active treatment, the patient finally improved diplopia and ptosis. LESSONS: This report marks the first documentation of oculomotor nerve palsy induced by imidacloprid, featuring diplopia, and blepharoptosis without substantial limitation of ocular motility. Following therapeutic intervention, the patient showed marked improvement and was discharged from the hospital, providing a point of reference for the treatment of analogous cases in future clinical practice. It also serves as a reminder for the public to take appropriate precautions when using imidacloprid.

Overexpression of SmUGGT1 Confers Imidacloprid Resistance to Sitobion miscanthi (Takahashi).

Sitobion miscanthi, the main species of wheat aphids, is one kind of harmful pest. Chemical insecticides are the important agrochemical products to effectively control wheat aphids. However, the broad application has led to serious resistance of pests to several insecticides, and understanding insecticide resistance mechanisms is critical for integrated pest management. In this study, SmUGGT1, a new uridine diphosphate (UDP)-glycosyltransferase (UGT) gene, was cloned and more strongly expressed in the SM-R (the resistant strain to imidacloprid) than in the SM-S (the susceptible strain to imidacloprid). The increased susceptibility to imidacloprid was observed after silencing SmUGGT1, indicating that it can be related to the resistance to imidacloprid. Subsequently, SmUGGT1 regulated post-transcriptionally in the coding sequences (CDs) by miR-81 was verified and involved in the resistance to imidacloprid in S. miscanthi. This finding is crucial in the roles of UGT involved in insecticide resistance management in pests.

Efficacy of novel insecticides against piercing sucking insects and their natural enemies on sweet pepper plants under field conditions.

Piercing sucking pests attacking sweet pepper plants cause significant losses to its yield. Considering the undesirable effects of synthetic pesticides, field studies were conducted to evaluate the impact of new pesticides against piercing sucking insect pests of sweet pepper, as well as, their effects on some predators and pepper yield along two seasons of 2021-2022. The obtained results indicated that all tested pesticides effectively suppressed the sucking insect populations (aphids, white fly, thrips) 1,7,14 and 21 days after treatment along two sprays during two seasons. Imidacloprid proved to be the superior one over all other treatments where it recorded mean reduction% (98.91 and 97.27%) & (94.8 and 95.19%), (86.23 and 76.64%) & (80.92 and 88.55%) and (77.68 and 78.44%) & (90.70 and 68.57%) in white fly, aphids and thrips, respectively at 1st and 2nd sprays at 2021 and 2022 seasons, respectively. As for side effects of tested insecticides on natural enemies, Dimethoate induced the highest decrease (60.85 and 69.33%) & (54.02 and 63.41%), (65.52 and 64.74%) & (59.23 and 58.38%) and (64.24 and 59.48%) & (61.66 and 60.8%) on Chrysoperla carnea, Paederus alfierii and Coccinella spp at 1st and 2nd sprays at 2021 and 2022 seasons, respectively. On contrary, Spintoram induced the lowest effects on Chrysoperla carnea, Paederus alfierii and Coccinella spp, recording decrease percent (25.41 and 19.84%) & (15.02 and 12.50%), (11.94 and 11.24%) (16.99 and 18.02%) and (18.73 and15.07%) & (18.35 and18.38%) at1st and 2nd sprays at 2021 and 2022 seasons, respectively. With respect to the effect of tested insecticides on pepper yield, all tested insecticides increased the yield of green pepper fruits compared with control. Imidacloprid achieved the highest fruit yields along two seasons 6.43 and 6.52 (ton / fed.4200 m2) with increase percent 34.53 and 36.04% in yield over control at 2021 and 2022 seasons, respectively.

Efficacy of selected pesticides on Citrus Brown Mite, Eutetranychus orientalis (Acari: Tetranychidae) and the side effects on three predatory mites under citrus orchard conditions.

The present study has been conducted to evaluate the effect of two sprays of seven pesticides at recommended dose on citrus brown mite, Eutetranychus orientalis and the side effects on their predatory mites, Euseius scutalis, Amblyseius swirskii, Phytoseiulus persimilis (Acari: Phytoseiidae) under field conditions at 2022 & 2023 seasons. The obtained results show that, all tested pesticides achieved high reduction % of E. orientalis ranged between (82.1-90.0%) and (81.6-87.1%) after the 1st and 2nd sprays of 2022 season, where it ranged between (84.9- 88.7%) and ( 79.7- 88.7%) after 1st and 2nd sprays of 2023 season. Abamectin recorded the highest reduction % against the citrus brown mite, whereas Congest pesticide recorded the lowest reduction % after the two sprays along 2022 & 2023 seasons. As for the side effects of tested pesticides on associated predatory mites, all pesticides were safely for E. scutalis numbers recording decrease % between (18.4-28.6%) and (16.2 -26.1%) after the 1st and 2nd spray at 2022 season , where it ranged between (15.3- 29.1%) and (19.6-32.0%) after the 1st and 2nd sprays of 2023 season. On contrary, imidacloprid was unsafely for E. scutalis numbers recording the highest mean decrease % after 1st and 2nd sprays during the two seasons. Also, all tested pesticides were safely for A. swirskii numbers, after the 1st and 2nd sprays of the two seasons recording decrease (from 10.9 to 28.1%) & (24.4 to 31.4%) for the 2022 season, and (19-38.9%) & (18.7-39.4%) at 2023 season. On contrary, imidacloprid was unsafely for A. swirskii numbers recorded the highest decrease % after 1st and 2nd sprays during the two seasons. As for, Ph. Persimilis numbers, all tested pesticides were safely, where it recorded low decrease % ranged between (17-33.8%) & (20.4-34.8%) after the 1st and 2nd sprays of 2022 season, and (24.3-39%) & (20.2-28.9%) after the 1st and 2nd sprays of 2023 season. On the other side, imidacloprid was unsafely for Ph. persimilis numbers recording the highest decrease % after the 1st and 2nd sprays during the two seasons. The present study proved that all tested pesticides were high effective against E. orientalis and appeared to be safely and selective for associated predatory mites except imidacloprid which was very harmful for all tested predatory mites, and it could be concluded that the tested pesticides, Fenpyroximate, Hexythiazox , Congest , Spirodiclofen, Abamectin, and Chlorfenapyr could be used in the Integrated Pest Management (IPM) programs for E. orientalis at citrus orchards.

Detection of N-desethyl etonitazene in a drug checking sample: Chemical analysis and pharmacological characterization of a recent member of the 2-benzylbenzimidazole "nitazene" class.

The emergence of 2-benzylbenzimidazole "nitazene" opioids is stirring up the recreational synthetic opioid market. Many nitazene analogues act as potent agonists at the µ­opioid receptor (MOR), as demonstrated in various in vitro and in vivo studies. Severe intoxication and overdose deaths associated with nitazene analogues are increasingly being reported. Nitazene opioids are classified as a public health threat, stressing the need for close monitoring of new developments on the recreational drug market. This study reports on the detection of N-desethyl etonitazene in a sample handed in by a recreational drug user at a Swiss drug checking service in August 2023. The person bought the sample through an internet source where it was stated to contain isotonitazene. Chemical analyses were conducted to characterize the sample, i.e. nuclear magnetic resonance (NMR), capillary electrophoresis (CE), and high-resolution mass spectrometry (HRMS). The sample was additionally investigated using two different in vitro MOR activation assays. NMR and high-performance liquid chromatography (HPLC) coupled to HRMS confirmed the presence of N-desethyl etonitazene at a high purity and in the absence of isotonitazene and etonitazene. N-Desethyl nitazene analogues have been detected before as metabolites of isotonitazene and etonitazene. However, as first seen with N-desethyl isotonitazene, they are now emerging as standalone drugs. The applied bioassays demonstrated increased efficacy and approximately 6-9-fold higher potency of N-desethyl etonitazene at MOR compared to fentanyl. N-Desethyl etonitazene showed EC50 values of 3.35 nM and 0.500 nM in the ß-arrestin 2 recruitment and Aequoscreen® assays, respectively. The opioid activity present in the collected sample was additionally evaluated using the bioassays and showed good overlap with the reference standard, in line with the analytical purity assessment. This demonstrates the potential of these bioassays to provide a rapid opioid activity assessment of authentic samples. The emergence of other N-desethyl nitazene analogues must be considered during forensic and clinical toxicology casework, to avoid misclassification of intake of such analogues as metabolites. Finally, drug checking services enable the close monitoring of market developments and trends and are of great value for early warning and harm reduction purposes.

[Determination of eight neonicotinoid pesticides in wastewater by solid phase extraction combined with liquid chromatography-tandem mass spectrometry].

Neonicotinoid pesticides are a relatively new class of pesticides that have garnered significant attention owing to their potential ecological risks to nontarget organisms. A method combining solid phase extraction with liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) was developed for the rapid and accurate detection of eight neonicotinoid pesticides (dinotefuran, E-nitenpyram, thiamethoxam, clothianidin, imidacloprid, imidaclothiz, acetamiprid, and thiacloprid) in wastewater. The chromatographic mobile phase and MS parameters were selected, and a single-factor method was used to determine the optimal column type, extraction volume, sample loading speed, and pH for SPE. The optimal parameters were as follows: column type, HLB column (500 mg/6 mL); sample extraction volume, 500 mL; sample loading speed, 10 mL/min; and sample pH, 6-8. The matrix effects of the wastewater samples were reduced by optimizing the chromatographic gradient-elution program, examining the dilution factor of the samples, and using the isotope internal standard calibration method. Prior to analysis, the wastewater samples were diluted 5-fold with ultrapure water for pretreatment. Subsequently, 2 mmol/L ammonium acetate aqueous solution containing 0.1% (v/v) formic acid and methanol was used as mobile phases for gradient elution on a ZORBAX Eclipse Plus C18 column (100 mm×2.1 mm, 1.8 µm). The samples were quantified using positive-ion multiple reaction monitoring (MRM) mode for 10 min. Imidacloprid-d4 was used as the isotope internal standard. The SPE process was further optimized by applying response surface methodology to select the type and mass of rinsing and elution solvents. The optimal pretreatment of the SPE column included rinsing with 10% methanol aqueous solution and elution with methanol-acetonitrile (1∶1, v/v) mixture (7 mL). The eight neonicotinoid pesticides showed satisfactory linearity within the relevant range, with linear correlation coefficients (r) all greater than 0.9990. The method detection limits (MDLs) ranged from 0.2 to 1.2 ng/L, and the method quantification limits (MQLs) ranged from 0.8 to 4.8 ng/L. The average recoveries of the eight neonicotinoid pesticides were in the range of 82.6%-94.2% at three spiked levels, with relative standard deviations (RSDs) ranging from 3.9% to 9.4%. Finally, the optimized method was successfully applied to analyze wastewater samples collected from four sewage treatment plants. The results indicated that the eight neonicotinoid pesticides could be generally detected at concentrations ranging from not detected (ND) to 256 ng/L. The developed method has a low MDL and high accuracy, rendering it a suitable choice for the trace detection of the eight neonicotinoid pesticides in wastewater when compared with other similar methods. The proposed method can be utilized to monitor the environmental impact and assess the potential risks of neonicotinoid pesticides in wastewater, thus promoting the protection of nontarget organisms and the sustainable use of these pesticides in agriculture.

Emerging therapeutic avenues against Cryptosporidium: A comprehensive review.

Cryptosporidium is among the top causes of life-threatening diarrheal infection in public health and livestock sectors. Despite its high prevalence and economic importance, currently, there is no vaccine. Control of this protozoan is difficult due to the excretion of many resistant oocysts in the feces of the infected host, which contaminate the environment. Paromomycin shows inconsistent results and isn't considered a reliable therapy for cryptosporidiosis. Nitazoxanide (NTZ), the only FDA-approved drug against this parasite, is less productive in impoverished children and PLWHA (people living with HIV/AIDS). The absence of mitochondria and apicoplast, its unique location inside enterocytes separated by parasitophorous vacuole, and, most importantly, challenges in its genetic manipulations are some hurdles to the drug-discovery process. A library of compounds has been tested against Cryptosporidium during in vitro and in vivo trials. However, there has still not been sufficient success in finding the drug of choice against this parasite. Recent genome editing technologies based on CRISPR/Cas-9 have explored the functions of the vital genes by producing transgenic parasites that help to screen a collection of compounds to find target-specific drugs, provided the sufficient availability of in vitro culturing platforms, efficient transfection methods, and analytic techniques. The use of herbal remedies against Cryptosporidium is also an emerging area of interest with sufficient clinical success due to enhanced concern regarding anthelmintic resistance. Here, we highlighted present treatment options with their associated limitations, the use of genetic tools and natural products against it to find safe, effective, and inexpensive drugs to control the ever-increasing global burden of this disease.

A cucurbit[6]uril-based fluorescence supramolecular assembly for information encryption and visualization detection of nitro compounds and antibiotics.

A novel CB[6]-based supramolecular assembly [K(ANS)(CB[6])2(DMF)2(H2O)0.5] (1) (CB[6] = cucurbit[6]uril, ANS- = 8-amino-1-naphthalene sulfonic acid ion) was successfully synthesized under solvothermal condition. Performance studies have shown that 1 exhibited excellent chemical stability and recycling performance. Meanwhile, 1 exhibited remarkable potential as a fluorescence sensor for the detection of 2,4,6-trinitrophenol (TNP), 4-nitrophenol (4-NP), and rifampicin (RFP) in both aqueous environments and practical samples. This sensing capability is achieved through fluorescence quenching, which offers fast response times and exceptional sensitivity, with detection limits of 0.19 µM for both TNP and 4-NP, and 0.21 µM for RFP. Even more remarkably, an anti-counterfeiting ink based on 1 and a portable test hydrogel were devised for encrypting information and visually detecting using a smartphone application. This work has the potential to expand the utilization of CB[6]-based materials in optical applications.

Silymarin ameliorates motor function and averts neuroinflammation-induced cell death in the rat model of Huntington's disease.

Huntington's disease (HD) is a scarce neurodegenerative disorder defined by chorea (unusual involuntary movements), behavioral presentations, psychiatric features, and cognitive deterioration. Although the precise pathogenic mechanism behind HD has not yet been identified, the most widely acknowledged pathways include excitotoxicity, mitochondrial malfunction, neuroinflammation, neurochemical imbalance, oxidative stress, and apoptosis HD has no efficient therapy. Current medications have drawbacks. Silymarin, a compound made up of standardized extracts obtained from the seeds of the Silybum marianum and polyphenolic flavonolignan, is utilized in therapeutic settings to treat a variety of experimental disorders in animals. Silymarin's key pharmacological activities include anti-cancer, hepatoprotection, antioxidant, cardioprotection, and anti-inflammatory. It also has no adverse side effects on people or animals. The current study aims to provide Silymarin's neuro-pharmacological activities or therapeutic qualities in HD. In this study, Thirty-six male Sprague-Dawley rats (200-220 g, 8 weeks) at the initial of the study were used. Silymarin solution (100 mg/Kg) was administered by oral gavage for 21 days to ameliorate neural damage in rats injected with 3-nitropropionicacid (3-NP) in a preliminary rat model of HD. The results showed that administration of silymarin to HD rats reduced gliosis, improved motor coordination and muscle activity, and increased striatal volume and the number of neurons and glial cells. Our results suggest that silymarin provides a protective environment for nerve cells and can have beneficial effects against the harmful effects of HD.