Pesticide residues in vegetables from Gansu province, China and risk assessment by Monte Carlo simulation.

To assess the dietary exposure risks of pesticide residues in vegetables for the general population, the presence of 39 pesticides was determined in 70 samples, of which 13 were detected. The most frequently detected pesticide was bifenthrin, with a detection rate of 35.7%, mainly found in gingers, followed by isoprocarb and acephate (11.4%) and dimethoate (8.6%). In 17.1% of the samples two or more pesticide residues were found. Acute, chronic and chronic cumulative dietary exposure risk was assessed. Chronic exposure risks were determined by Monte Carlo Simulation (MCS). Estimated chronic exposure to carbofuran, omethoate, disulfoton and dimethoate of approximately 49%, 52%, 40% and 3%, respectively, were at non-carcinogenic human risk. Acute exposure risk to acephate was considered to be of concern due to the high acute hazard quotient (aHQ).

Comparative transcriptome profiling of two pesticides, Acephate and Chlorantraniliprole in non-targeted insect model, Drosophila melanogaster.

Acephate and chlorantraniliprole are two insecticides widely used in agricultural applications. Several studies were focused on the mode of action and related biological and cellular level expressions. However, the sub-lethal dose and related molecular expression level of acephate and chlorantraniliprole have not been evaluated or studied to the same degree. In this study, we investigated the sub-lethal toxicity of acephate and chlorantraniliprole in Drosophila melanogaster. The EC50 value was recorded with high difference, and is found to be 1.9 µg/ml and 0.029 µg/ml respectively for acephate and chlorantraniliprole, the difference is simply because of the different modes of action. The 1/5th EC50 concentration was selected for studying the pesticide induced transcriptomics in D. melanogaster. Both pesticides significantly altered the expression profile of several transcripts which are involved in proteolysis, detoxification, chromosome associated proteins and immune response genes and so on. The effect of both pesticides on D. melanogaster was further explored by screening the genes involved in toxicity, which were analyzed using, GO and KEGG pathways. The results revealed that the sub-lethal exposure of both pesticides caused significant changes in the global gene transcription profiles and each pesticide had their unique mode of alteration in the D. melanogaster.

Removal of acephate and methamidophos from water: Coagulation and adsorptive treatment approaches.

Pesticides has transformed the agricultural industry, primarily by enhancing productivity. However, the indiscriminate use of such compounds can adversely affect human health and disrupt ecosystem balance. Limited knowledge exists regarding the removal of these compounds from water, particularly for organophosphate pesticides when employing conventional treatment technologies. Therefore, this study aimed to assess the removal of acephate (ACE) and methamidophos (MET) - considered priority pesticides in Brazil - from waters with high and low turbidity during the clarification process carried out with aluminum sulfate (AS) and ferric chloride (FC), either alone or combined with powdered activated carbon (PAC) adsorption. All water samples were submitted to solid phase extraction (SPE C18 cartridges) prior to acephate and methamidophos analysis by HPLC MS/MS. The clarification process with either AS or FC coagulant did not efficiently remove acephate or methamidophos and maximum average removal (27 %) was observed with waters of high turbidity when using ferric chloride as coagulant. Addition of mineral PAC was also ineffective for removing both pesticides. However, the use of vegetable PAC (10 mg/L) resulted in better removal percentages, up to 80%, but only for methamidophos. The limited removal rates were attributed to the high hydrophilicity of acephate and methamidophos, along with their neutral charge at coagulation pH. These factors hinder the interaction of such organophosphorus pesticides with the flocs formed during coagulation as well as with PAC surface.

Effectiveness and residual activity of four common insecticides used in the Mississippi Delta to control tarnished plant bugs in cotton.

The tarnished plant bug, (TPB) Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae) is a key pest of cotton in the midsouth region and some areas of the eastern United States. Its control methods have been solely based on chemical insecticides which has contributed to insecticidal resistance and shortened residual periods for control of this insect pest. This study was conducted over a two-year period and examined the efficacy and residual effect of four commercial insecticides including lambda-cyhalothrin (pyrethroid), acephate (organophosphate), imidacloprid (neonicotinoid), and sulfoxaflor (sulfoxamine). The effectiveness and residual effects of these insecticides were determined by application on cotton field plots on four different dates during each season using three different concentrations (high: highest labeled commercial dose (CD), medium: 1/10 of the CD, low: 1/100 of the CD) on field cotton plots. Four groups of cotton leaves were randomly pulled from each treated plot and control 0-, 2-, 4-, 7-, and 9-days post treatment (DPT) and exposed to a lab colony of TPB adults. One extra leaf sample/ plot/ spray /DPT interval (0-2-4-7-9-11) during 2016 was randomly collected from the high concentration plots and sent to Mississippi State Chemical Laboratory for residual analysis. Mortality of TPB adults was greatest for those placed on leaves sprayed with the organophosphate insecticide with mortalities (%) of 81.7±23.4 and 63.3±28.8 (SE) 1-day after exposure (DAE) on leaves 0-DPT with the high concentration for 2016 and 2017, respectively, reaching 94.5±9.5 and 95.4±7.6 6-DAE each year. Mortality to all insecticides continued until 9 and 4-DPT for high and medium concentrations, respectively. However, organophosphate (39.4±28.6) and pyrethroid (24.4±9.9) exhibited higher mortality than sulfoxamine (10.6±6.6) and the neonicotinoid (4.0±1.5) 7-DAE on 9-DPT leaves with the high concentration. Based on our results using the current assay procedure, TPB adults were significantly more susceptible to contact than systemic insecticides and due to its residual effect, organophosphate could kill over 80% of the TPB population 7-DPT.

Coating of maize seeds with acephate for precision agriculture: Safety assessment in earthworms, bees, and soil microorganisms.

Acephate is commonly used as a seed treatment (ST) in precision agriculture, but its impact on pollinators, earthworms, and soil microorganisms remains unclear. This study aimed to compare the fate of acephate seed dressing (SD) and seed coating (SC) treatments and assess potential risks to bees, earthworms, and soil microorganisms. Additionally, a follow-up study on maize seeds treated with acephate in a greenhouse was conducted to evaluate the maize growth process and the dissipation dynamics of the insecticide. The results indicated that acephate SC led to greater uptake and translocation in maize plants, resulting in lower residue levels in the soil. However, high concentrations of acephate metabolites in the soil had a negative impact on the body weight of earthworms, whereas acephate itself did not. The potential risk to bees from exposure to acephate ST was determined to be low, but dose-dependent effects were observed. Furthermore, acephate ST had no significant effect on soil bacterial community diversity and abundance compared to a control. This study provides valuable insights into the uptake and translocation of acephate SD and SC, and indicates that SC is safer than SD in terms of adverse effects on bees and nontarget soil organisms.

Microbial detoxification of chlorpyrifos, profenofos, monocrotophos, and dimethoate by a multifaceted rhizospheric Bacillus cereus strain PM38 and its potential for the growth promotion in cotton.

Bacillus genera, especially among rhizobacteria, are known for their ability to promote plant growth and their effectiveness in alleviating several stress conditions. This study aimed to utilize indigenous Bacillus cereus PM38 to degrade four organophosphate pesticides (OPs) such as chlorpyrifos (CP), profenofos (PF), monocrotophos (MCP), and dimethoate (DMT) to mitigate the adverse effects of these pesticides on cotton crop growth. Strain PM38 exhibited distinct characteristics that set it apart from other Bacillus species. These include the production of extracellular enzymes, hydrogen cyanide, exopolysaccharides, Indol-3-acetic acid (166.8 µg/mL), siderophores (47.3 µg/mL), 1-aminocyclopropane-1-carboxylate deaminase activity (32.4 µg/mL), and phosphorus solubilization (162.9 µg/mL), all observed at higher concentrations. This strain has also shown tolerance to salinity (1200 mM), drought (20% PEG-6000), and copper and cadmium (1200 mg/L). The amplification of multi-stress-responsive genes, such as acdS, ituC, czcD, nifH, sfp, and pqqE, further confirmed the plant growth regulation and abiotic stress tolerance capability in strain PM38. Following the high-performance liquid chromatography (HPLC) analysis, the results showed striking compatibility with the first kinetic model. Strain PM38 efficiently degraded CP (98.4%), PF (99.7%), MCP (100%), and DMT (95.5%) at a concentration of 300 ppm over 48 h at 35 °C under optimum pH conditions, showing high coefficients of determination (R2) of 0.974, 0.967, 0.992, and 0.972, respectively. The Fourier transform infrared spectroscopy (FTIR) analysis and the presence of opd, mpd, and opdA genes in the strain PM38 further supported the potential to degrade OPs. In addition, inoculating cotton seedlings with PM38 improved root length under stressful conditions. Inoculation of strain PM38 reduces stress by minimizing proline, thiobarbituric acid-reactive compounds, and electrolyte leakage. The strain PM38 has the potential to be a good multi-stress-tolerant option for a biological pest control agent capable of improving global food security and managing contaminated sites.

Semi-rational design for enhancing thermostability of Culex pipiens acetylcholinesterase and sensitivity analysis of acephate.

Acetylcholinesterase (AChE) has emerged as a significant biological recognition element in the biosensor field, particularly for the detection of insecticides. Nevertheless, the weak thermostability of AChE restricts its utilization due to the complexities associated with production, storage, and application environments. By evaluating the binding affinity between representative AChE and insecticides, an AChE from Culex pipiens was screened out, which displayed a broad-spectrum and high sensitivity to insecticides. The C. pipiens AChE (CpA) was subsequently expressed in Escherichia coli (E. coli) as a soluble active protein. Furthermore, a three-point mutant, M4 (A340P/D390E/S581P), was obtained using a semi-rational design strategy that combined molecular dynamics (MD) simulation and computer-aided design, which exhibited a four-fold increase in half-life at 40 °C compared to the wild-type (WT) enzyme. The mutant M4 also demonstrated an optimal temperature of 50 °C and a melting temperature (Tm) of 51.2 °C. Additionally, the sensitivity of WT and M4 to acephate was examined, revealing a 50-fold decrease in the IC50 value of M4. The mechanism underlying the improvement in thermal performance was elucidated through secondary structure analysis and MD simulations, indicating an increase in the proportion of protein helices and local structural rigidity. MD analysis of the protein-ligand complexes suggested that the enhanced sensitivity of M4 could be attributed to frequent specific contacts between the organophosphorus (OP) group of acephate and the key active site residue Ser327. These findings have expanded the possibilities for the development of more reliable and effective industrial enzyme preparations and biosensors.

How the chemical structure of phosphoramides affect the fire retardancy and mechanical properties of polylactide?

Phosphoramides, as a kind of high-efficient fire retardants, have been designed in many structures and endowed exceptional fire retardancy to polylactide (PLA). However, due to ignorance of the structure-property correlation, the effect of phosphoramides' structure on the fire retardancy and mechanical properties of PLA is still unclear. Herein, a series of biobased phosphoramides (phosphoramide (V1), linear polyphosphoramide (V2) and hyperbranched polyphosphamide (V3)) were designed and incorporated into PLA, and the structural effect of phosphoramides on the fire-retardant and mechanical properties of PLA was deeply researched. Among three kinds of phosphoramides, the hyperbranched polyphosphoramide is more effective than the corresponding linear polyphosphoramide and phosphoramide in improving the fire-retardant and anti-dripping properties of PLA, and only linear polyphosphoramide shows a positive effect in the mechanical strength of PLA. This work provides a feasible strategy for creating mechanically robust and fire-retardant polymer composites by molecularly tailoring the structure of fire retardants and uncovering their structure-property relationship.

Evaluating the fire resistance and durability of cotton textiles treated with a phosphoramide phosphorus ester phosphate ammonium flame retardant.

The phosphoramide phosphorus ester phosphate ammonium (PPEPA) flame retardant was synthesized by phosphorus oxychloride and ethanolamine, and its structure was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy (FTIR). Cotton textiles treated with 20 wt% PPEPA (CT-PPEPA3) would have high durability and flame retardance. The limiting oxygen index (LOI) of CT-PPEPA3 was found to be 46.5 %, while after undergoing 50 laundering cycles (LCs) following the AATCC 61-2013 3 A standard, the LOI only decreased to 31.4 %. Scanning electron microscopy and X-ray diffraction analyses suggested the penetration of PPEPA molecules into the interior of cotton fibers, resulting in a minor alteration of the cellulose crystal structure. The excellent durability, FTIR, and energy-dispersive X-ray of CT-PPEPA3 provided evidence for the formation of -N-P(=O)-O-C- and -O-P(=O)-O-C- covalent bonds between the PPEPA molecules and cellulose. The -N-P(=O)-O-C- bond exhibited a p-π conjugation effect, leading to enhanced stability and improved durability of the flame-retardant cotton textiles. Vertical flame, thermogravimetric, and cone calorimetry tests demonstrated that the CT-PPEPA3 underwent condensed-phase and synergistic flame retardation. Additionally, these finished cotton textiles retained adequate breaking strength and softness, making them suitable for various applications. In conclusion, the incorporation of the -N-P(=O)-ONH4 group into the phosphorus ester phosphate ammonium flame retardant demonstrated effective enhancement of the fire resistance and durability of treated cotton textiles.

Phosphoramidate Azole Oligonucleotides for Single Nucleotide Polymorphism Detection by PCR.

Detection of the Kirsten rat sarcoma gene (KRAS) mutational status is an important factor for the treatment of various malignancies. The most common KRAS-activating mutations are caused by single-nucleotide mutations, which are usually determined by using PCR, using allele-specific DNA primers. Oligonucleotide primers with uncharged or partially charged internucleotide phosphate modification have proved their ability to increase the sensitivity and specificity of various single nucleotide mutation detection. To enhance the specificity of single nucleotide mutation detection, the novel oligonucleotides with four types of uncharged and partially charged internucleotide phosphates modification, phosphoramide benzoazole (PABA) oligonucleotides (PABAO), was used to prove the concept on the KRAS mutation model. The molecular effects of different types of site-specific PABA modification in a primer or a template on a synthesis of full-length elongation product and PCR efficiency were evaluated. The allele-specific PCR (AS-PCR) on plasmid templates showed a significant increase in analysis specificity without changes in Cq values compared with unmodified primer. PABA modification is a universal mismatch-like disturbance, which can be used for single nucleotide polymorphism discrimination for various applications. The molecular insights of the PABA site-specific modification in a primer and a template affect PCR, structural features of four types of PABAO in connection with AS-PCR results, and improvements of AS-PCR specificity support the further design of novel PCR platforms for various biological targets testing.

Bemnifosbuvir (BEM, AT-527), a novel nucleotide analogue inhibitor of the hepatitis C virus NS5B polymerase.

INTRODUCTION: Chronic hepatitis C virus (HCV) persists as a public health concern worldwide. Consequently, optimizing HCV therapy remains an important objective. While current therapies are generally highly effective, advanced antiviral agents are needed to maximize cure rates with potentially shorter treatment durations in a broader patient population, particularly those patients with advanced diseases who remain difficult to treat. AREAS COVERED: This review summarizes the in vitro anti-HCV activity, preclinical pharmacological properties of bemnifosbuvir (BEM, AT-527), a novel prodrug that is metabolically converted to AT-9010, the active guanosine triphosphate analogue that potently and selectively inhibits several viral RNA polymerases, including the HCV NS5B polymerase. Results from clinical proof-of-concept and phase 2 combination studies are also discussed. EXPERT OPINION: BEM exhibits potent pan-genotype activity against HCV, and has favorable safety, and drug interaction profiles. BEM is approximately 10-fold more potent than sofosbuvir against HCV genotypes (GT) tested in vitro. When combined with a potent NS5A inhibitor, BEM is expected to be a promising once-daily oral antiviral for chronic HCV infection of all genotypes and fibrosis stages with potentially short treatment durations.

Properties of phosphoramide benzoazole oligonucleotides (PABAOs). I. Structure and hybridization efficiency of N-benzimidazole derivatives.

In this work, we for the first time conducted a detailed study on the structure, dynamics, and hybridization properties of N-benzimidazole group-bearing phosphoramide benzoazole oligonucleotides (PABAOs) that we developed recently. By circular dichroism we established that the introduction of the modifications does not disrupt the B conformation of the DNA double helix. The formation of complexes is approximated by a two-state model. Complexes of PABAOs with native oligodeoxriboynucleotides form efficiently, and the introduction of such modifications reduces thermal stability of short duplexes (8-10 bp) by ∼5°Ð¡ per modification. Using UV-spectroscopy analysis, a neutral charge of the phosphate residue modified by the N-benzimidazole moiety in the pH range of 3-9.5 was found. The results confirm possible usefulness of PABAOs for both basic research and biomedical applications.

Rapid Biodegradation of the Organophosphorus Insecticide Acephate by a Novel Strain Burkholderia sp. A11 and Its Impact on the Structure of the Indigenous Microbial Community.

The acephate-degrading microbes that are currently available are not optimal. In this study, Burkholderia sp. A11, an efficient degrader of acephate, presented an acephate-removal efficiency of 83.36% within 56 h (100 mg·L-1). The A11 strain has a broad substrate tolerance and presents a good removal effect in the concentration range 10-1600 mg·L-1. Six metabolites from the degradation of acephate were identified, among which the main products were methamidophos, acetamide, acetic acid, methanethiol, and dimethyl disulfide. The main degradation pathways involved include amide bond breaking and phosphate bond hydrolysis. Moreover, strain A11 successfully colonized and substantially accelerated acephate degradation in different soils, degrading over 90% of acephate (50-200 mg·kg-1) within 120 h. 16S rDNA sequencing results further confirmed that the strain A11 gradually occupied a dominant position in the soil microbial communities, causing slight changes in the diversity and composition of the indigenous soil microbial community structure.

Anti-cancer Activity of New Phosphoramide-functionalized Graphene Oxides: An Experimental and Theoretical Evaluation.

BACKGROUND: Graphene oxide (GO)-based systems are among the drug delivery systems and have drawn a lot of interest in the field of medicine. METHODS: In this work, two novel phosphoramides with the formulas of (NHCHCH2C(CH3)2NHC(CH3)2CH2P(S)(OEt)2 (L1) and (NHCHCH2C(CH3)2 NHC (CH3)2CH2P (O) (NHC6H5) (OC5H6) (L2) were synthesized and characterized by spectroscopic methods. Then, graphene oxide (GO) was functionalized by L1 and L2. FT-IR, XRD, FE- SEM/ MAP, and Zeta potential analyses were applied to confirm the synthesis of phosphoramide-functionalized graphene oxides (GO-L1 and GO-L2). Cytotoxicity of synthesized compounds was evaluated against breast cancer cell line (SK-BR-3) using MTT assay. Moreover, the flow cytometry assay was performed to evaluate the cell death mechanisms. RESULTS: The results showed that GO-L1 and GO-L2 had a more inhibitory effect against cancer cells than that of L1 and L2, and GO-L2 showed the highest cytotoxicity with an IC50 value of 38.13 µg/ml. Quantum calculations were employed to optimize structures. HOMO and LUMO energy values and physical adsorption of synthesized compounds were obtained by the DMol3 module in the Material Studio 2017. The docking studies were used to investigate the binding of L1, L2, GO-L1, and GO-L2 to DNA polymerase IIα. CONCLUSION: Anticancer activity of phosphoramide compounds was increased after attachment on the GO surface, and the docking studies' results were in good accordance with the experimental cytotoxicity results.

GCMC and electronic evaluation of pesticide capture by IRMOF systems.

Environmental contamination by pesticides is a recurrent problem, and a way to minimize its impacts and provide the reduction of contaminants already in the environment is a challenge. In this context, porous materials such as metal-organic frameworks (MOFs) have gained prominence. MOFs can carry the pesticide when physically or chemically interacting with its pore sites, enabling pesticide capture. However, evaluating the best MOF to maximize the process is an important step that can be performed under computer simulation. This work used grand canonical Monte Carlo simulations to assess the interaction between glyphosate, atrazine, acephate, and dichlorodiphenyltrichloroethane pesticides with the structures of IRMOF-1, IRMOF-8, IRMOF-10, and IRMOF-16. These MOFs present several organic unit types, which generate different pore volumes with similar chemical environment. For glyphosate, atrazine, and acephate, a direct relationship was shown between the pore volume and the amount of captured pesticide, which is a direct contribution from the strong interaction between the pesticides. Higher pore volumes maximize glyphosate, atrazine, and acephate capture. Otherwise, for dichlorodiphenyltrichloroethane, the larger the pore volume, the smaller the amount of pesticide is loaded. The interaction between all pesticides and IRMOFs is mainly governed by van der Waals contribution, being more pronounced for glyphosate, atrazine, and acephate molecules.

Standardized Field Trials in Cotton and Bioassays to Evaluate Resistance of Tobacco Thrips (Thysanoptera: Thripidae) to Insecticides in the Southern United States.

Foliar-applied insecticide treatments may be necessary to manage thrips in cotton (Gossypium hirsutum L.) under severe infestations or when at-planting insecticide seed treatments do not provide satisfactory protection. The most common foliar-applied insecticide is acephate. Field observations in Tennessee suggest that the performance of acephate has declined. Thus, the first objective was to perform leaf-dip bioassays to assess if tobacco thrips, Frankliniella fusca (Hinds) (Thysanoptera: Thripidae), in cotton production regions have evolved resistance to foliar-applied insecticides. A second objective was to assess the performance of commonly applied foliar insecticides for managing thrips in standardized field trials in Arkansas, Tennessee, Mississippi, and Texas. For both objectives, several insecticides were evaluated including acephate, dicrotophos, dimethoate, lambda-cyhalothrin, imidacloprid, and spinetoram. Field trials and bioassays were completed from 2018 to 2021. Dose-response bioassays with acephate were performed on tobacco thrips field populations and a susceptible laboratory population. Bioassay results suggest that tobacco thrips have developed resistance to acephate and other organophosphate insecticides; however, this resistance seems to be most severe in Arkansas, Tennessee, and the Delta region of Mississippi. Resistance to other classes of insecticides were perhaps even more evident in these bioassays. The performance of these insecticides in field trials was variable, with tobacco thrips only showing consistent signs of resistance to lambda-cyhalothrin. However, it is evident that many populations of tobacco thrips are resistant to multiple classes of insecticides. Further research is needed to determine heritability and resistance mechanism(s).

[Current and future therapeutic options for COVID-19]. / Recente en toekomstige behandelingen bij covid-19.

The anti-inflammatory agents dexamethasone (corticosteroid), and tocilizumab and sarilumab (IL6-inhibitors) are effective in the treatment of late COVID-19. Other anti-inflammatory agents, like anakinra (IL1-inhibitor), baricitinib and tofacitinib (JAK-inhibitors) and lenzilumab (GM-CSF-inhibitor) have also shown positive results in late COVID-19. For the treatment of early COVID-19, the inhalation corticosteroid budesonide is regarded as an off-label treatment option. Virus-inhibitors, like remdesivir, molnupiravir and nirmatrelvir/ritonavir decrease the risk of hospitalization and the development of severe COVID-19 by patients with early symptoms. Monoclonal antibodies have shown limited or no efficacy against the omicron-variant of SARS-CoV-2. Fluvoxamine, l-arginine, AT-527 and ensovibep are considered as potential promising new therapies for the treatment of early COVID-19.

Hazard Assessment of the Effects of Acute and Chronic Exposure to Permethrin, Copper Hydroxide, Acephate, and Validamycin Nanopesticides on the Physiology of Drosophila: Novel Insights into the Cellular Internalization and Biological Effects.

New insights into the interactions between nanopesticides and edible plants are required in order to elucidate their impacts on human health and agriculture. Nanopesticides include formulations consisting of organic/inorganic nanoparticles. Drosophila melanogaster has become a powerful model in genetic research thanks to its genetic similarity to mammals. This project mainly aimed to generate new evidence for the toxic/genotoxic properties of different nanopesticides (a nanoemulsion (permethrin nanopesticides, 20 ± 5 nm), an inorganic nanoparticle as an active ingredient (copper(II) hydroxide [Cu(OH)2] nanopesticides, 15 ± 6 nm), a polymer-based nanopesticide (acephate nanopesticides, 55 ± 25 nm), and an inorganic nanoparticle associated with an organic active ingredient (validamycin nanopesticides, 1177 ± 220 nm)) and their microparticulate forms (i.e., permethrin, copper(II) sulfate pentahydrate (CuSO4·5H2O), acephate, and validamycin) widely used against agricultural pests, while also showing the merits of using Drosophila-a non-target in vivo eukaryotic model organism-in nanogenotoxicology studies. Significant biological effects were noted at the highest doses of permethrin (0.06 and 0.1 mM), permethrin nanopesticides (1 and 2.5 mM), CuSO4·5H2O (1 and 5 mM), acephate and acephate nanopesticides (1 and 5 mM, respectively), and validamycin and validamycin nanopesticides (1 and 2.5 mM, respectively). The results demonstrating the toxic/genotoxic potential of these nanopesticides through their impact on cellular internalization and gene expression represent significant contributions to future nanogenotoxicology studies.

IDentif.AI-Omicron: Harnessing an AI-Derived and Disease-Agnostic Platform to Pinpoint Combinatorial Therapies for Clinically Actionable Anti-SARS-CoV-2 Intervention.

Nanomedicine-based and unmodified drug interventions to address COVID-19 have evolved over the course of the pandemic as more information is gleaned and virus variants continue to emerge. For example, some early therapies (e.g., antibodies) have experienced markedly decreased efficacy. Due to a growing concern of future drug resistant variants, current drug development strategies are seeking to find effective drug combinations. In this study, we used IDentif.AI, an artificial intelligence-derived platform, to investigate the drug-drug and drug-dose interaction space of six promising experimental or currently deployed therapies at various concentrations: EIDD-1931, YH-53, nirmatrelvir, AT-511, favipiravir, and auranofin. The drugs were tested in vitro against a live B.1.1.529 (Omicron) virus first in monotherapy and then in 50 strategic combinations designed to interrogate the interaction space of 729 possible combinations. Key findings and interactions were then further explored and validated in an additional experimental round using an expanded concentration range. Overall, we found that few of the tested drugs showed moderate efficacy as monotherapies in the actionable concentration range, but combinatorial drug testing revealed significant dose-dependent drug-drug interactions, specifically between EIDD-1931 and YH-53, as well as nirmatrelvir and YH-53. Checkerboard validation analysis confirmed these synergistic interactions and also identified an interaction between EIDD-1931 and favipiravir in an expanded range. Based on the platform nature of IDentif.AI, these findings may support further explorations of the dose-dependent drug interactions between different drug classes in further pre-clinical and clinical trials as possible combinatorial therapies consisting of unmodified and nanomedicine-enabled drugs, to combat current and future COVID-19 strains and other emerging pathogens.

Roles of phosphoramide derivatives in flame retardancy, thermal degradation and crystallization behaviors of polylactic acid.

Two kinds of phosphoramide derivatives containing one (POFA) or two (BPOFA) phosphoramide bonds were synthesized using diphenylphosphinic chloride, phenylphosphonic dichloride and furfurylamine, respectively. The flame retardancy, thermal degradation and crystallization behaviors of polylactic acid (PLA)/POFA and PLA/BPOFA blends were investigated using the limiting oxygen index (LOI), UL-94 vertical burning tests, cone calorimeter tests, thermogravimetric analysis and differential scanning calorimetry. A small amount of 1.0 wt% BPOFA increases the LOI of PLA from 20.4 vol% to 28.0 vol% and achieves the UL-94 V0 rating, while 7.0 wt% POFA is needed to achieve the UL-94 V0 rating indicating that the PLA/BPOFA has better flame retardancy than that of PLA/POFA. Both POFA and BPOFA decrease the amount of flammable gaseous compounds and play positive roles in transesterification of PLA. More importantly, BPOFA is easier to catalyze the degradation of PLA and improve UL-94 rating by melting-away mode. Moreover, the BPOFA accelerates the crystallization rate and thus improves the crystallinity of PLA, while POFA does not show a positive effect on crystallization behaviors of PLA.