Low Lethal Dose Research Articles

Structural, spectroscopic, and biological properties of an asymmetric Cu (II) Schiff-base complex: Synthesis, DNA/BSA interactions, and antimicrobial potential with experimental and computational insights

A copper (II) complex with the asymmetric bidentate Schiff-base ligand (E)-2-(((4-chlorophenyl) imino) methyl) phenol was synthesized and characterized using FTIR and UV–VIS spectroscopy. Photoluminescence studies were conducted on both the copper (II) complex and the free ligand. XRD analysis revealed the copper (II) complex crystallizes in the monoclinic system, space group P21/c. The complex structure was optimized using DFT calculations with B3LYP/6-31G+(d,p) and Lanl2dz basis sets, with QTAIM and NBO analyses confirming complex formation. The energy gap of the copper (II) complex was determined to be 3.701 eV (alpha state) and 2.764 eV (beta state). MEP analysis of the optimized structure indicated a hydrophobic environment around the nitrogen atom, with the molecule exhibiting overall hydrophobicity. The chlorine atoms were identified as potential nucleophilic sites. The antimicrobial efficacy of a Schiff base copper (II) complex was evaluated against selected pathogenic bacteria (B. subtilis, B. megaterum, K. pneumoniae, E. coli) and the fungus Candida albicans. Among these C. albicans for complex showed larger zones (11–15.5 mm) at higher concentrations such as 2 and 2.5 mg/mL. Molecular docking studies suggested strong binding affinity between the complex and the target protein, this was further supported by obtained root means square deviations, root means square fluctuations, radius of gyration and hydrogen bond values during simulations. The binding free energy between BSA and the copper (II) complex was calculated as −8.7 kcal/mol, indicating significant interaction. However, only weak van der Waals interactions were observed between the complex and DNA. Toxicity studies revealed the copper (II) complex had minimal irritant effects on ocular and cutaneous tissues, with a low lethal dose. In comparison, Tricresyl phosphate showed moderate to severe ocular irritancy and modest cutaneous irritancy.

Detoxification of Paraquat: Scooping up the Moon from the Water?

Review Detoxification of Paraquat: Scooping up the Moon from the Water? Yanyan Zhu and Xiuping Chen * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 519000, China * Correspondence: xpchen@um.edu.mo; Tel.: +853-88224679 Received: 9 May 2024; Revised: 6 June 2024; Accepted: 12 June 2024; Published: 23 August 2024 Abstract: Paraquat poisoning is a global public health problem, particularly in the Asia-Pacific region. Ingestion of even small amounts of paraquat can be life-threatening. However, there is no specific antidote for this pesticide, which has a low lethal dose and high lethality in humans. Paraquat poisoning causes systemic toxicity with the primary target organ being the lungs, resulting in acute alveolitis and pulmonary fibrosis. It can also lead to multiple organ failure. This review summarizes the current clinical management of patients with paraquat poisoning and the potentially effective compounds reported in the literature and patents for the treatment of paraquat poisoning. It also summarizes future directions for antidote development based on reports of available potential antidotes and provides ideas for paraquat antidote development.

Systematic screening of synthetic organochalcogen compounds with anticancer activity using human lung adenocarcinoma spheroids

Lung adenocarcinoma stands as a leading global cause of cancer-related fatalities, with current therapeutic approaches remaining unsatisfactory. Given the association between elevated oxidative markers and the aggressive nature of cancer cells (including multidrug resistance and metastatic potential) that can predict poor outcome of lung adenocarcinoma patients, any compounds that interfere with their aberrant redox biology should be rationally explored as innovative intervention strategies. This study was designed to screen potential anticancer activities within nine newly synthesized organochalcogen – compounds characterized by the presence of oxygen, sulfur, or selenium elements in their structure and exhibiting antioxidant activity – and systematically evaluated their performance against cisplatin, the cornerstone therapeutic agent for lung adenocarcinoma. Our methodology involved the establishment of optimal conditions for generating single tumor spheroids using A549 human lung adenocarcinoma cell line. The initiation interval for spheroid formation was determined to be four days in vitro (DIV), and these single spheroids demonstrated sustained growth over a period of 20 DIV. Toxic dose-response curves were subsequently performed for each compound after 24 and 48 h of incubation at the 12th DIV. Our findings reveal that at least two of the synthetic organochalcogen compounds exhibited noteworthy anticancer activity, surpassing cisplatin in key parameters such as lower LD (Lethal Dose) 50, larger drug activity area, and maximum amplitude of effect, and are promising drugs for futures studies in the treatment of lung adenocarcinomas. Physicochemical descriptors and prediction ADME (absorption, distribution, metabolism, and excretion) parameters of selected compounds were obtained using SwissADME computational tool; Molinspiration server was used to calculate a biological activity score, and possible molecule targets were evaluated by prediction with the SwissTargetPrediction server. This research not only sheds light on novel avenues for therapeutic exploration but also underscores the potential of synthetic organochalcogen compounds as agents with superior efficacy compared to established treatments.

Galleria mellonella Model of Coccidioidomycosis for Drug Susceptibility Tests and Virulence Factor Identification.

Coccidioidomycosis (CM) can manifest as respiratory and disseminated diseases that are caused by dimorphic fungal pathogens, such as Coccidioides species. The inhaled arthroconidia generated during the saprobic growth phase convert into multinucleated spherules in the lungs to complete the parasitic lifecycle. Research on coccidioidal virulence and pathogenesis primarily employs murine models typically associated with low lethal doses (LD100 < 100 spores). However, the Galleria model has recently garnered attention due to its immune system bearing both structural and functional similarities to the innate system of mammals. Our findings indicate that Coccidioides posadasii can convert and complete the parasitic cycle within the hemocoel of the Galleria larva. In Galleria, the LD100 is between 0.5 and 1.0 × 106 viable spores for the clinical isolate Coccidioides posadasii C735. Furthermore, we demonstrated the suitability of this model for in vivo antifungal susceptibility tests to validate the bioreactivity of newly discovered antifungals against Coccidioides. Additionally, we utilized this larva model to screen a Coccidioides posadasii mutant library showing attenuated virulence. Similarly, the identified attenuated coccidioidal mutants displayed a loss of virulence in a commonly used murine model of coccidioidomycosis. In this study, we demonstrated that Galleria larvae can be applied as a model for studying Coccidioides infection.

An Overview on the Worlds Dead Liest Poison (Palytoxin and its Analogs)

Abstract: Palytoxin is a marine toxin found originally in soft corals Palythoa species of the Pacific Ocean. It is a thermostable, non-protein, coronary vasoconstrictor that leads to death by diminishing the supply of O2 to the Myocardium. Several analogs of PTX or PTLX such as Ostreocin-D, Ovatoxin are found in several dinoflagellates and other marine species such as Crabs (Demania reynaudii) and Smoked Fishes (Decapterus macrosoma) found in same ecological regions. Toxicological studies of PTX showed low lethal dose values in different mammals revealing the acute toxicity due to different routes of exposure. On exposure to PTX, symptoms such as Rhabdomyolysis (high dose), Na+- K+ pump and heart failure &amp; other symptoms including abdominal cramps, vomiting, bradycardia, etc. are seen in Pescatarians. There is no particular antidote for the PTX compounds, but these compounds can be neutralized by the household bleach solution. Activated Carbon absorbed 99.7% of palytoxin in aquarium waters. In this paper, we review the current knowledge on Palytoxin &amp; its analogs. In recent years, many methodologies have been described for the development of new techniques for the detection of palytoxin based on LC-MS/MS and a bio-technique Immunoassay.

The joint action effects of bioprotective agents on life table indices of Trogoderma granarium Everts (Coleoptera: Dermestidae)

Using nature-based substances (diatomaceous earth) and entomopathogenic fungi as grain bioprotective factors in a mixed mode is imperative to manage stored product pests in terms of preserving food safety. Trogoderma granariumEverts (Coleoptera: Dermestidae) biological traits and life table indices of parent and progeny were assessed after exposure toBeauveria bassiana(strain DE) (Hypocreales) dry conidia (LD50 = 295.3 mg conidia kg-1 grain), low lethal dose (mg dust kg-1 grain) of diatomaceous earth formulations including Sayan® (LD25 = 4439.5), and Celite® 610 (LD25 = 992) and their binary mixtures. According to the lethal dose ratio test (LD50), the insecticidal activity of Celite® 610 has 4.47 times more than Sayan®. Nearly all binary mixes exhibited synergistic effects, excluding the last dose of the fungus (LD90), which additively interacted. However, totalpre-adults (days), adults' longevity, and reproductive performance of the beetle were decreased drastically, particularly in a combination of LD50B. bassiana + LD25Celite®610. Besides, the vital progeny population's indices, such as intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and gross reproduction rate (GRR), all were decreased similarly. The lowest r (-0.0004 day −1) and R0 (0.968 offspring per individual) were found in the B. bassiana mixture with a low-lethal dose of Celite® 610. The male-biased sex ratio was notably established after adults' exposure to binary mixtures. Our results demonstrated that both parent and offspring generation of T. granarium incur fitness costs through exposure tobioprotectivesubstancesand especially their mixed modes, resulting in effective suppressing of the adult populations.

Rapid and sensitive detection of botulinum toxin type A in complex sample matrices by AlphaLISA.

Botulinum toxin A(BoNT/A) is a neurotoxin produced by the bacteria Clostridium botulinum, which can cause serious food poisoning and is recognized as a potential biological warfare agent. BoNT/A is does not degrade easily and can remain in the complex matrix for a long time. Meanwhile, the poisonous dose of botulinum toxin exceptionally low and intravenous human lethal doses estimated at 1-3 ng/kg. Therefore, sensitive and accurate detection methods suitable for testing a wide range of complex samples are urgently needed. To this end, the "amplified luminescent proximity homogeneous assay linked immunosorbent assay" (AlphaLISA) was established for the detection of BoNT/A and its detection efficacy in plasma, beverage, food, and other complex samples was evaluated. The results showed that this method can very effectively resist matrix interference. The detection time is rapid, reaching a detection limit for all samples of up to 0.1 ng/mL in only 30 min. BoNT/A can also be accurately detected in vomit samples of patients with clinical food poisoning. This study demonstrates that AlphaLISA is an effective tool for the detection of BoNT/A in complex samples and can potentially be developed for commercial use in the future.

Pathogen Prevalence Modulates Medication Behavior in Ant Formica fusca.

Ants face unique challenges regarding pathogens, as the sociality which has allowed them to form large and complex colonies also raises the potential for transmission of disease within them. To cope with the threat of pathogens, ants have developed a variety of behavioral and physiological strategies. One of these strategies is self-medication, in which animals use biologically active compounds to combat pathogens in a way which would be harmful in the absence of infection. Formica fusca are the only ants that have previously been shown to successfully self-medicate against an active infection caused by a fungal pathogen by supplementing their diet with food containing hydrogen peroxide. Here, we build on that research by investigating how the prevalence of disease in colonies of F. fusca affects the strength of the self-medication response. We exposed either half of the workers of each colony or all of them to a fungal pathogen and offered them different combinations of diets. We see that workers of F. fusca engage in self-medication behavior even if exposed to a low lethal dose of a pathogen, and that the strength of that response is affected by the prevalence of the disease in the colonies. We also saw that the infection status of the individual foragers did not significantly affect their decision to forage on either control food or medicinal food as uninfected workers were also foraging on hydrogen peroxide food, which opens up the possibility of kin medication in partially infected colonies. Our results further affirm the ability of ants to self-medicate against fungal pathogens, shed new light on plasticity of self-medication and raise new questions to be investigated on the role self-medication has in social immunity.

Developmental Cardiotoxicity and Hepatotoxicity of Flurbiprofen Axetil to Zebrafish Embryo.

Flurbiprofen axetil (FA) is a nonsteroidal targeted analgesic and widely used for postoperative analgesia and cancer analgesia. Extensive works have been done in the evaluation of FA's clinical analgesic effect on adults. Along with the increase of FA usage, the potential toxicity and molecular mechanism in embryo development need to be better understood. In this article, multiple embryonic development indexes of zebrafish were introduced to evaluate the FA toxicity to provide clinical guidance for gravidas medicine. We performed a zebrafish embryo toxicity (ZFET) test by exposing embryos to a series of concentration gradients of FA medium starting from 24 hours postfertilization (hpf). The mortality rate, hatching rate, and malformation rate of drug-treated zebrafish were assessed at 72, 96, and 120 hpf. Effects of ≤10% lethal concentration (LC10) of FA on embryogenesis were evaluated by eye area, body length, and yolk sac area. A 0.5 μg/mL or fewer FA treatment did not show any adverse effects, but the LC10 FA significantly caused zebrafish malformation. Organ disorders, including slow heart rate, enlarged pericardium, and liver atrophy, were found in the dysplasia individuals when compared with control. TUNEL assay suggested that apoptotic cells in malformation embryos were produced by FA and the increasing dosage exacerbated apoptosis. Quantitative real-time polymerase chain reaction revealed that expressions of cardiac development-associated transcription factors, liver development-related genes, and apoptosis regulating genes were aberrant. These results indicate that the ZFET can be applied in the FA toxicity test, and a low lethal dose of FA is harmful to zebrafish embryogenesis, especially in embryo carcinogenesis and hepatogenesis.

Global Warming and Toxicity Impacts: Peanuts in Georgia, USA Using Life Cycle Assessment

Fertilizers and pesticides have been widely used in agriculture production, causing polluted soil, water, and atmosphere. This study aims to quantify air emissions from pesticides and fertilizers applied for peanut production in Georgia during selected years (1991, 1999, 2004, 2013, and 2018). Specifically, the oral and dermal potential impacts from pesticide emissions and the global warming potential (GWP) impact from fertilizers to air were investigated. This study followed the ISO 14040 series standards for life cycle assessment (LCA) methodology to assess six active ingredients (AIs) (2,4-DB, Bentazon, Chlorothalonil, Ethalfluralin, Paraquat, and Pendimethalin) and one greenhouse gas (nitrous oxide N2O). Their physical and chemical characteristics and the temporal scales greatly influenced the oral and dermal toxicity impacts. According to the low values obtained for Henry’s law (KH) and vapor pressure (VP), 2,4-dichlorophenoxy butanoic (DB), Pendimethalin, and Chlorothalonil have a higher impact on the continental air scale. The effect factor (EF) from oral exposure was higher in 2,4-DB, Bentazon, and Pendimethalin than dermal exposure, according to the relatively low lethal dose (LD50) for oral exposure, while the EF of Ethalfluralin and Chlorothalonil was the same for oral and dermal exposure according to their similar LD50.

Effect of Three Types of Ion Beam Irradiation on Gerbera (Gerbera hybrida) In Vitro Shoots with Mutagenesis Efficiency.

Gerbera in vitro shoots were irradiated using three types of ion beams with different line energy transfers (LETs) to investigate the effective LET and absorbed doses for mutagenesis. Furthermore, genomic mutation analyses were conducted on the obtained mutants. Survival rate analysis showed a lower lethal dose 50% (LD50) with ion beams with higher LETs. Trait/morphological mutations exhibited changes in the color and shape of petals and male sterility. Irradiation conditions with the highest growth change and trait/morphological mutation rates in each ion were C irradiation at 10 Gy, Ar irradiation at 5 Gy, and Fe irradiation at 5 Gy, with a range of absorbed dose of around LD50 to about 10 Gy lower. The highest trait/morphological mutation rate was 14.1% with Ar irradiation at 5 Gy, which was one of the criteria for ion beam irradiation of gerbera in vitro shoots. Furthermore, the genomic mutation in the flower color, petal shape, and male sterile mutants were confirmed by genotype analysis using Genotyping by Random Amplicon Sequencing-Direct technology. This is the first study to report the efficient production of gerbera mutants that could be analyzed. Our findings may lead to more efficient gerbera mutant production and analysis technology.

Calculation of the Median Lethal Dose and Low Lethal Dose Using the CombiStats Biometric Software

The median lethal dose (LD50) and low lethal dose (LD10) are calculated in acute toxicity studies, as well as during specific activity assessment of some medicines. The aim of the study was to develop a procedure for using CombiStats to calculate LD50 and LD10. The authors proposed a step-by-step algorithm for processing bioassay results using the CombiStats biometric software (median effective dose determination model, probit analysis) with conversion of doses to simple fractions (fractions of the maximum dose) to calculate LD50 and LD10. They compared LD50 and LD10 calculation results obtained using CombiStats with those obtained using electronic spreadsheets according to the Bliss–Miller–Tainter–Prozorovsky method described in the State Pharmacopoeia of the Russian Federation (General Monograph 1.1.0014.15). It has been demonstrated that the use of CombiStats sometimes has advantages over the use of the pharmacoepoeial method.

Exploration of Antioxidant and Anticancer Activity of Stephania japonica Leaves Extract

Aims: The demand for antioxidants from the natural source has drawn promising attention to outturn desired pharmacological effect by subsidizing the adverse effect for treating cancer. This study evaluated the antioxidant activity of Stephania japonica leaves extracts to explore the anticancer activity. &#x0D; Methods: Antioxidant potential of crude extracts were evaluated using various methods which include total antioxidant activity, ferric reducing antioxidant assay, DPPH free radical, ABTS free radical, nitric oxide and superoxide anion radical scavenging assay. Anticancer activity was determined in vitro by MTT assay and in vivo on mice against Ehrlich ascites carcinoma (EAC) cell.&#x0D; Results: Phytoconstituents with free radical scavenging capacity were quantified in terms of inhibitory concentration (IC50) with the values of 17.00±3.22 µg/mL, 33.30 ± 5.45 µg/mL, 43.70±5.26 µg/mL and 52.30±1.07 µg/mL in DPPH, ABTS, superoxide anion radical and nitric oxide free radical scavenging assay, respectively as the highest quencher, acetone extract of S. japonica leaves (ASJL). ASJL and methanol extract (MSJL) showed low lethal dose (LD50) values of 21.76 and 26.63, respectively indicating higher toxicity. In vitro anti-proliferative activity (MTT assay), ASJL and MSJL were exhibited 15.44±2.96 to 80.94±2.87 and 11.76±3.74 to 74.25±1.49 percent of cell growth inhibition, respectively at the concentration of 10.28 µg/mL to 833.33 µg/mL. In in vivo test, ASJL and MSJL at the dose of 100 mg/kg/day and 200 mg/kg/day (i.p.) showed cell growth inhibition of 58.25±4.24% to 79.09±2.45% and 46.26±2.68% to 61.74±4.41%, respectively on EAC cell tumor-bearing mice. The life span of intraperitoneal induced EAC cell bearing mice was increased to 29.05% and 57.02% on the treatment of ASJL with 100 and 200 mg/kg/day, respectively.&#x0D; Conclusions: The free radical scavenger of S. japonica leaves extract was stimulated the host immunity and inhibited the EAC cell growth through initiating the apoptosis cell death program. Therefore, S. japonica leaves might be utilized as a potent anticancer natural source.

Acute and Subchronic Toxicity Studies of Combretum collinum Methanol Root Extract in Albino Rats

Combretum collinum root extract has been recognized long ago as traditional medicinal plant in curing several diseases among the indigenous people of Alela-land (Zuru), Kebbi State, Nigeria. This research work was carried out to evaluate the toxicological effects of Combretum collinum methanol root extract (CCME) in albino rats. Acute toxicity was performed by a fixed single oral administration at a dose of 10, 100, 1000 mg/Kg and 1600, 2900, 5000 mg/Kg. Subchronic toxicity studies of CCME was conducted at doses of 32, 63, 126 and 253 mg/Kg for 28 days. The result showed that acute administration of CCME resulted at mortality and general behavioral changes at 1000 to 5000 mg/Kg. Therefore, the estimated lethal dose (LD50) of CCME was 316.23 mg/Kg. Subchronic oral administration of CCME revealed a significant (P&lt;0.01) decrease in body weight in rats receiving 63 to 253 mg/Kg throughout the study period compared with the control group. The results also showed a significant (P&lt;0.01) increase in serum ALT, AST, creatinine, potassium and bicarbonate in rats administered with 126 and 253 mg/Kg of the extract. Haematological analysis of the same extract revealed a significant (P&lt;0.01) increase in WBC, HCT, MCV, MCH, MCHC, PLT, LYM and NEUT in rats receiving 126 and 253 mg/Kg only. Histopathological examination of liver revealed severe periportal inflammation, hypertrophy, areas of hydropic changes, cancerous tumor, areas of infiltration and necrosis of the hepatic cells while the kidney showed a mild mesengial hyperplasia, compressed blood vessels, glomerular degeneration, tubular degeneration and tubular widened lumen in rats treated with 63 to 253 mg/Kg. Therefore, caution should be applied as C. collinum root extract has a low mean lethal dose and would be toxic at higher concentrations.

Collimated Microbeam Reveals that the Proportion of Non-Damaged Cells in Irradiated Blastoderm Determines the Success of Development in Medaka (Oryzias latipes) Embryos.

Simple SummaryStudies on teratogenesis in mammals have revealed that exposure to ionizing radiation (IR) during the pre-implantation period induces a high frequency of lethality instead of teratogenesis. Here, to elucidate the IR-induced disturbance of embryonic development when IR exposure occurs during the pre-implantation period, we utilized medaka as a vertebrate model for clear observation of developmental process for its transparency. Blastula embryos exposed to IR with a lower lethal dose (gamma-rays) transiently exhibited smaller brains than those of sham-controls, however, their brain size restored equally to those of controls until hatching. We then conducted targeting irradiation, which allowed various proportions of blastoderm cells to be exposed to IR (carbon-ions), and identified that the loss of approximately 10% or less of blastoderm was compensated by the remaining non-damaged blastoderm cells even though they transiently exhibited smaller brains. In contrast, when IR exposure occurred during the late embryogenesis period, 3 days post fertilization, the brain size was not completely restored until hatching even with a lower lethal dose. Collectively, blastoderm cells with IR-induced injury undergo transient delays in brain development, however, can avoid teratogenesis at hatching presumably for their pluripotency whereas embryos during the late embryogenesis period lack the ability to do so.It has been widely accepted that prenatal exposure to ionizing radiation (IR) can affect embryonic and fetal development in mammals, depending on dose and gestational age of the exposure, however, the precise machinery underlying the IR-induced disturbance of embryonic development is still remained elusive. In this study, we examined the effects of gamma-ray irradiation on blastula embryos of medaka and found transient delay of brain development even when they hatched normally with low dose irradiation (2 and 5 Gy). In contrast, irradiation of higher dose of gamma-rays (10 Gy) killed the embryos with malformations before hatching. We then conducted targeted irradiation of blastoderm with a collimated carbon-ion microbeam. When a part (about 4, 10 and 25%) of blastoderm cells were injured by lethal dose (50 Gy) of carbon-ion microbeam irradiation, loss of about 10% or less of blastoderm cells induced only the transient delay of brain development and the embryos hatched normally, whereas embryos with about 25% of their blastoderm cells were irradiated stopped development at neurula stage and died. These findings strongly suggest that the developmental disturbance in the IR irradiated embryos is determined by the proportion of severely injured cells in the blastoderm.

Metarhizium (=Nomuraea) rileyi (Farlow) Samson from Spodoptera exigua (Hübner) Cross Infects Fall Armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) Larvae

Mycobiocontrol is a promising management strategy in mitigating the fall armyworm Spodoptera frugiperda (J.E. Smith) infestation in the Philippines. An isolate of Metarhizium (=Nomuraea) rileyi (Farlow) Samson from onion or beet armyworm, S. exigua, which induced high mortality to this pest, was assessed against different larval instars of S. frugiperda. Surface-sterilized corn leaves were treated with different conidial concentrations and fed to S. frugiperda larvae. Cross infection of this entomopathogenic fungus to S. frugiperda was confirmed with a fungal infection that was initiated at 1–2 d post-treatment depending on the age of the larvae. Larval mortality significantly increased at 4–5 d post-treatment. Up to 100% larval mortality was recorded at 7 d post-treatment. Early larval instars (1st–3rd) were more susceptible than late larval instars (4th–6th). Higher conidial concentrations caused a higher and faster rate of larval mortality than lower conidial concentrations. The inflicted mycoses due to M. rileyi resulted in a slightly lower lethal dose (LD50) (1.44 x 105 to 9.36 x 108 conidia ∙ mL–1) and shorter mean time to death (4.51–8.89 d). Mummification of the cadaver confirmed fungal infection with white fungal growth that later changed to green during sporulation. Our findings suggest the infectivity of M. rileyi and can be explored as a biological control agent against S. frugiperda.

Polychlorinated Biphenyl Electrochemical Aptasensor Based on a Diamond-Gold Nanocomposite to Realize a Sub-Femtomolar Detection Limit.

Polychlorinated biphenyls (PCBs) with high toxicity, low lethal dose, and bioaccumulation have been inhibited for application in wide fields, and a highly efficient trace detection is thus greatly desirable. In this study, we produce dense Au-nanoparticles by twice sputtering and twice annealing (T-Au-NPs) on boron-doped diamond (BDD). The successful formation of T-Au-NPs/BDD nanocomposites was confirmed by scanning electron microscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy analysis. Based on T-Au-NPs/BDD, an electronic biosensor with aptamers is fabricated to detect trace polychlorinated biphenyl-77 (PCB-77) by electrochemical impedance. A good linear relationship in the range of femtomolar to micromolar and significantly low detection limit of sub-femtomolar level (0.32 fM) are realized based on the biosensor. The emphasis of this research lies in the key role of the diamond substrate in the biosensor. It is demonstrated that the biosensor has excellent sensitivity, specificity, stability, and recyclability, which are favorable for detecting the trace PCB-77 molecule. It is attributed to the important effect presented by the BDD substrate and the synergistic influence of T-Au-NPs combined with aptamers.

Sublethal and transgenerational effects of lambda-cyhalothrin on the mirid bugs Lygus pratensis Linnaeus and Polymerus cognatus Fieber

The plant mirid bugs, Lygus pratensis Linnaeus and Polymerus cognatus Fieber, are key pests on economically important cotton crops and ecologically important grassland in northwestern China. Lambda-cyhalothrin is frequently used against mirid bugs in the regions. In this study, we examined the sublethal and transgenerational effects of short-term exposure to lambda-cyhalothrin on biological traits using a miminal dose, LD5 [0.484 ng/L. pratensis adult, and 0.171 ng/P. cognatus adult], a low lethal dose, LD25 [1.353 ng/L. pratensis adult, and 0.781 ng/P. cognatus adult] and a moderate lethal dose, LD50 [2.766 ng/L. pratensis adult, and 2.243 ng/P. cognatus adult]. Direct exposure to LD50 of lambda-cyhalothrin led to decreased adult longevity, shorter female oviposition period and lower fecundity of the parental generation for both species, whereas treatment with LD5 lambda-cyhalothrin stimulated female fecundity on L. pratensis, but not on P. cognatus. The F1 generation underwent transgenerational effects, i.e. there was delayed egg-laying period and larval development and decreased hatchability for both species, decreased adult longevity and fecundity for L. pratensis, and shortened adult longevity for the LD50 group of P. cognatus. Compared with the untreated control group, the net reproductive rate (R0), the intrinsic rate of increase (rm), and finite rate of increase (λ) were significantly decreased for the groups treated with different doses of lambda-cyhalothrin, whereas the generation time (T) was increased. Our results demonstrate that sublethal effects of lambda-cyhalothrin can retard development and suppress population growth for both of these mirid species. Therefore, this insecticide can be used effectively against mirid bugs in northern China and its application strategy to control mirid bug is discussed.

Guar gum micro-vehicle mediated delivery strategy and synergistic activity of thymoquinone and piperine: An in vitro study on bacterial and hepatocellular carcinoma cells

This study reports the observed synergy in antimicrobial and anticancer activity of thymoquinone and piperine, encapsulated in porous guar gum micro-vehicle. Natural therapeutics like piperine and thymoquinone showed less effectivity in human medical trials due to their hydrophobicity leading to poor clinical efficacy. To overcome this problem, we have developed a delivery strategy by using guar gum, a natural biodegradable biopolymer. The successful encapsulation of phytochemicals and the microstructures of gum micro-vehicles were confirmed by Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM) and UV–Vis spectra analysis. We also report here a significant decrease in minimum inhibitory concentration (MIC) value and synergistic bactericidal activity against four different bacterial strains and observed remarkably low median lethal dose (LD50) value against human hepatocellular carcinoma cell lines along with pH-responsive delivery of therapeutic in the case of combinatorial therapy. In our overall study, we analyze and discuss the structure, efficacy, and delivery of our designed natural therapeutic amalgamation to pave the way for augmenting the use of phytochemicals in medical applications.

High accuracy machine learning identification of fentanyl-relevant molecular compound classification via constituent functional group analysis

Fentanyl is an anesthetic with a high bioavailability and is the leading cause of drug overdose death in the U.S. Fentanyl and its derivatives have a low lethal dose and street drugs which contain such compounds may lead to death of the user and simultaneously pose hazards for first responders. Rapid identification methods of both known and emerging opioid fentanyl substances is crucial. In this effort, machine learning (ML) is applied in a systematic manner to identify fentanyl-related functional groups in such compounds based on their observed spectral properties. In our study, accurate infrared (IR) spectra of common organic molecules which contain functional groups that are constituents of fentanyl is determined by investigating the structure–property relationship. The average accuracy rate of correctly identifying the functional groups of interest is 92.5% on our testing data. All the IR spectra of 632 organic molecules are from National Institute of Standards and Technology (NIST) database as the training set and are assessed. Results from this work will provide Artificial Intelligence (AI) based tools and algorithms increased confidence, which serves as a basis to detect fentanyl and its derivatives.