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Ricin is a toxic protein regarded as a potential chemical weapon for bioterrorism or criminal use. In the event of a ricin incident, rapid analytical methods are essential for ricin confirmation in a diversity of matrices, from environmental to human or food samples. Mass spectrometry–based methods provide specific toxin identification but require prior enrichment by antibodies to reach trace-level detection in matrices. Here, we describe a novel assay using the glycoprotein asialofetuin as an alternative to antibodies for ricin enrichment, combined with the specific detection of signature peptides by high-resolution mass spectrometry. Additionally, optimizations made to the assay reduced the sample preparation time from 5 h to 80 min only. Method evaluation confirmed the detection of ricin at trace levels over a wide range of pH and in protein-rich samples, illustrating challenging matrices. This new method constitutes a relevant antibody-free solution for the fast and specific mass spectrometry detection of ricin in the situation of a suspected toxin incident, complementary to active ricin determination by adenine release assays. [ABSTRACT FROM AUTHOR]

The performance of MALDI-TOF MS combined with analysis platform for identification of toxin-producing Clostridiodes difficile is yet to be known. Between August 2018 and September 2020, 61 isolates from stool specimens of patients with C. difficile -associated diarrhea were analyzed using the MALDI Biotyper system. A C. difficile toxin-producer detection model was developed using ClinProTools. The model was validated using 28 known strains that differed from the isolates used to develop the model. The sensitivity and specificity of the Genetic Algorithm (GA) model using isolates grown on Brucella with hemin and vitamin K (BHK) agar plates were 91.7% and 44.4%, respectively. When isolates grown on cycloserine-cefoxitin mannitol agar were analyzed by the model, sensitivity and specificity were 6.3% and 100%, respectively. The GA model using BHK medium showed the highest discriminatory performance in detection of toxin-producing C. difficile. However, a discrepancy in detection of toxin-producing C. difficile was observed in the results generated when the model was being developed and when the model was validated which suggests that incubation conditions may have affected the results. MALDI-TOF analysis using ClinProTools has a potential to be a cost-effective tool for rapid diagnosis and contribute to antimicrobial stewardship by differentiating toxin-producing C. difficile from non-producers. [ABSTRACT FROM AUTHOR]

Bisphenol-A (BPA) is a synthetically manufactured phenolic substance that is very widely employed in producing polycarbonate polymers and epoxy resins which further can be found in numerous items of daily use such as foodstuff and their containers, beverages, milk, audit rolls, dental fillings and so forth. Additionally, it is present in the air we breathe-in. The studies have reported that BPA produces toxic impacts on reproductive, cardiovascular, endocrine, renal, gastrointestinal, immune, respiratory, nervous and skeletal system. In the current literature review, we have targeted to highlight the protective role of herbs in opposition to BPA toxicity. The gift of nature-'Plants' seem to be very efficient and potential agents to overcome the BPA induced toxicity as they themselves are devoid of adverse effects. Plants contain a mixture of phyto-molecules which together act to provide a synergistic effect. Further, we have explained the signaling mechanisms implicated in BPA toxicity. Even though, multiple mechanisms involved in BPA toxicity have been examined, no particular target therapy for this toxicity is available at present. Thus, naturally occurring substances may be looked at in the future for restorative use to mitigate the deleterious and negative consequences of exposure to BPA. [ABSTRACT FROM AUTHOR]

Forssman was a Swedish pathologist and microbiologist who, in the 1920s and 1930s conducted a long series of experiments that led to unique insights into surface antigens of blood cells, as well as added to the discrimination of toxins produced by staphylococci that lyse red blood cells. This review takes offset in the studies published by Forssman in APMIS addressing the hemolytic properties of staphylococcal toxins displayed against erythrocytes of animal and human origin. In light of current knowledge, we will discuss the insights we now have and how they may pave the way for curing infections with pathogenic staphylococci, including Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Toxin-antitoxin (TA) modules are widely found in the genomes of pathogenic bacteria. They regulate vital cellular functions like transcription, translation, and DNA replication, and are therefore essential to the survival of bacteria under stress. With a focus on the type II parDE modules, this study thoroughly examines TAome in Pseudomonas aeruginosa, a bacterium well-known for its adaptability and antibiotic resistance. We explored the TAome in three P. aeruginosa strains: ATCC 27,853, PAO1, and PA14, and found 15 type II TAs in ATCC 27,853, 12 in PAO1, and 13 in PA14, with significant variation in the associated mobile genetic elements. Five different parDE homologs were found by further TAome analysis in ATCC 27,853, and their relationships were confirmed by sequence alignments and precise genomic positions. After comparing these ParDE modules’ sequences to those of other pathogenic bacteria, it was discovered that they were conserved throughout many taxa, especially Proteobacteria. Nucleic acids were predicted as potential ligands for ParD antitoxins, whereas ParE toxins interacted with a wide range of small molecules, indicating a diverse functional repertoire. The interaction interfaces between ParDE TAs were clarified by protein-protein interaction networks and docking studies, which also highlighted important residues involved in binding. This thorough examination improves our understanding of the diversity, evolutionary dynamics, and functional significance of TA systems in P. aeruginosa, providing insights into their roles in bacterial physiology and pathogenicity. [ABSTRACT FROM AUTHOR]

Sea anemones are an important source of bioactive compounds with potential pharmacological applications. Their toxins are produced and stored in organelles called nematocysts and act on specific targets, including voltage-gated ion channels. To date, sea anemone toxins have demonstrated effects on voltage-gated sodium and potassium channels, facilitating investigations into the structure and function of these proteins. In this study, we evaluated the effect of Bunodeopsis globulifera sea anemone crude extract, and of a low molecular weight fraction, on voltage-gated sodium and calcium channels within the murine nervous system. Notably, the crude extract led to a significant reduction in total sodium current, while also triggering calcium-dependent glutamate release. Furthermore, the low molecular weight fraction, in particular, enhanced total calcium currents and current density. These findings underscore the existence of sea anemone toxins with diverse mechanisms of action beyond those previously documented. [ABSTRACT FROM AUTHOR]

Ananteris is a scorpion genus that inhabits dry and seasonal areas of South and Central America. It is located in a distinctive morpho-group of Buthids, the 'Ananteris group', which also includes species distributed in the Old World. Because of the lack of information on venom composition, the study of Ananteris species could have biological and medical relevance. We conducted a venomics analysis of Ananteris platnicki, a tiny scorpion that inhabits Panama and Costa Rica, which shows the presence of putative toxins targeting ion channels, as well as proteins with similarity to hyaluronidases, proteinases, phospholipases A2, members of the CAP-domain family, and hemocyanins, among others. Venom proteolytic and hyaluronidase activities were corroborated. The determination of the primary sequences carried out by mass spectrometry evidences that several peptides are similar to the toxins present in venoms from Old World scorpion genera such as Mesobuthus, Lychas, and Isometrus, but others present in Tityus and Centruroides toxins. Even when this venom displays the characteristic protein families found in all Buthids, with a predominance of putative Na+-channel toxins and proteinases, some identified partial sequences are not common in venoms of the New World species, suggesting its differentiation into a distinctive group separated from other Buthids. [ABSTRACT FROM AUTHOR]

In recent years, the production and demand of berries in the world have gradually increased, but the infection of fungal pathogens has become one of the important factors restricting the production and sales of fresh berries. It has been found that Alternaria can cause a variety of plant diseases and fruit rot worldwide. This review introduces the effect of Alternaria infection on berry quality, including physical, chemical and physiological aspects, and discusses the possible infection mechanisms. In addition, Alternaria produces toxins during infections and seriously threatens the safety of berries and consumer health. Therefore, the prevention and control measures of Alternaria are systematically summarized. This review provides the basis for further optimization of postharvest preservation technology and fruit quality, to prolong the shelf life of berries. We can realistically expect to control plant diseases with increasing efficiency, which is conducive to improving the quality and safety of postharvest berry fruits. [ABSTRACT FROM AUTHOR]

Mammary tumors are the most frequent type of neoplasms in intact female dogs. New therapies that target neoplastic cells without affecting normal cells are highly sought. The Bacillus anthracis toxin has been reengineered to target tumor cells that express urokinase plasminogen activators and metalloproteinases. In previous studies carried out in our laboratory, the reengineered anthrax toxin had inhibitory effects on canine oral mucosal melanoma and canine osteosarcoma cells. In this study, five canine neoplastic epithelial cell lines (four adenocarcinomas and one adenoma) and one non-neoplastic canine mammary epithelial cell line were treated with different concentrations of reengineered anthrax toxin components. Cell viability was quantified using an MTT assay and half-maximal inhibitory concentration (IC50) values. Cell lines were considered sensitive when the IC50 was lower than 5000 ng/ml. One canine mammary adenocarcinoma cell line and one mammary adenoma cell line showed significantly decreased viability after treatment, whereas the non-neoplastic cell line was resistant. We conclude that the reengineered anthrax toxin may be considered a targeted therapy for canine mammary neoplasms while preserving normal canine mammary epithelial cells. [ABSTRACT FROM AUTHOR]

Background and Aims: Klebsiella oxytoca (K. oxytoca) is the second bacterial cause of nosocomial infections in the general population after K. pneumoniae. This study surveyed the frequency of cytotoxin‐producing strains of K. oxytoca and their antibiotic susceptibility profile in a cohort of children admitted to a referral hospital with different malignancies. Methods: The Stool samples of children admitted to the Cancer Chemotherapy Unit of the Mofid Children's Hospital, Tehran, Iran were analyzed using conventional biochemical tests and polymerase chain reaction targeting the pehX gene to identify K. oxytoca. The antibiotic susceptibility profile of isolated K. oxytoca against commonly prescribed antibiotics used in treating infection at the facility was determined using the Kirby–Bauer disk diffusion technique. Also, the prevalence of genes encoding toxins among K. oxytoca was identified by PCR assay. Results: The Stool samples of 280 participants were taken for the study of which 38 samples [(55.3% (21/38) 42 males and 44.7% (17/38) females)] tested positive for various Klebsiella spp. Out of this, K. oxytoca was identified in 2.5% (7/280) stools using cultures and conventional biochemical tests. Also, the stools of 2.9% (8/280) of the participants tested positive for K. oxytoca using PCR assay. Using PCR, (2/7) of the K. oxytoca isolates tested positive for the npsA and npsB genes and were identified as toxigenic K. oxytoca strains. Conclusion: The prevalence of toxin‐producing K. oxytoca strains in stool samples of children diagnosed with cancer in Iran is relatively low. Most of the K. oxytoca isolates were susceptible to tested antibiotics. Globally, active surveillance of toxigenic K. oxytoca strains in patients with different malignancies or immunocompromised patients is recommended in healthcare settings. [ABSTRACT FROM AUTHOR]

An isolate of a Gram-positive, strictly aerobic, motile, rod-shaped, endospore forming bacterium was originally isolated from soil when screening and bioprospecting for plant beneficial microorganisms. Phylogenetic analysis of the 16S rRNA gene sequences indicated that this strain was closely related to Lysinibacillus fusiformis NRRL NRS-350T (99.7%) and Lysinibacillus sphaericus NRRL B-23268T (99.2%). In phenotypic characterization, the novel strain was found to grow between 10 and 45 °C and tolerate up to 8% (w/v) NaCl. Furthermore, the strain grew in media with pH 5 to 10 (optimal growth at pH 7.0). The predominant cellular fatty acids were observed to be iso-C15: 0 (52.3%), anteiso-C15: 0 (14.8%), C16:1ω7C alcohol (11.2%), and C16: 0 (9.5%). The cell-wall peptidoglycan contained lysine-aspartic acid, the same as congeners. A draft genome was assembled and the DNA G+C content was determined to be 37.1% (mol content). A phylogenomic analysis on the core genome of the new strain and 5 closest type strains of Lysinibacillus revealed this strain formed a distinct monophyletic clade with the nearest neighbor being Lysinibacillus fusiformis. DNA–DNA relatedness studies using in silico DNA–DNA hybridizations (DDH) showed this species was below the species threshold of 70%. Based upon the consensus of phylogenetic and phenotypic analyses, we conclude that this strain represents a novel species within the genus Lysinibacillus, for which the name Lysinibacillus pinottii sp. nov. is proposed, with type strain PB211T (= NRRL B-65672T, = CCUG 77181T). [ABSTRACT FROM AUTHOR]

Sensitively detecting hazardous and suspected bioaerosols is crucial for safeguarding public health. The potential impact of pollen on identifying bacterial species through fluorescence spectra should not be overlooked. Before the analysis, the spectrum underwent preprocessing steps, including normalization, multivariate scattering correction, and Savitzky–Golay smoothing. Additionally, the spectrum was transformed using difference, standard normal variable, and fast Fourier transform techniques. A random forest algorithm was employed for the classification and identification of 31 different types of samples. The fast Fourier transform improved the classification accuracy of the sample excitation–emission matrix fluorescence spectrum data by 9.2%, resulting in an accuracy of 89.24%. The harmful substances, including Staphylococcus aureus, ricin, beta-bungarotoxin, and Staphylococcal enterotoxin B, were clearly distinguished. The spectral data transformation and classification algorithm effectively eliminated the interference of pollen on other components. Furthermore, a classification and recognition model based on spectral feature transformation was established, demonstrating excellent application potential in detecting hazardous substances and protecting public health. This study provided a solid foundation for the application of rapid detection methods for harmful bioaerosols. [ABSTRACT FROM AUTHOR]

The high mortality rate in cattle and buffalo is a concern, especially in developing countries, such as Egypt. Under conditions of global change in climatic conditions, has caused the activation of some opportunistic microbes, causing deaths in cattle and buffalo farms. As a result of environmental stressors which lead to the activation of some bacterial agents which is the main reason for the increase in mortality in this article, we reported special spots on some bacterial agents causing sudden death in cattle and buffalo. Fecal and nasal discharge samples were collected for bacteriological examination from (60 diseased cattle and buffalo showing clinical signs of respiratory and diarrheic symptoms 30 from each of different ages and sexes (first group) and 40, slaughtered or dead animals (cattle and buffalo) from ruminal contents, tissue samples from liver, spleen, and lung 20 from each (second group). We collected samples from many locations at Assiut Governorate and were sent to the laboratory. The results of the first group indicated that (50) 30 cattle and 20 buffalo were positive for bacterial infection however 10 showed negative results of bacterial infection in buffalo. The incidence of bacterial infection in the first group was 83.5%, whereas the second group indicated that 100% (40) (20 cattle and 20 buffalo) were positive for bacterial infection. Bacteriological investigations of first group revealed that the isolated organisms were: Clostridium perfringens (46.7%), Pasteurella multocida (33.3%), Escherichia coli (13.3%), Salmonella sp.(6.7%) in cattle but in buffalo recorded that Clostridium perfringens (33.3%), Pasteurella multocida (23.3%), Escherichia coli (6.7%), Salmonella sp.( 3.3%), On other hand, bacteriological investigations of second group revealed that the isolated organisms were: Clostridium perfringens (50%), Pasteurella multocida (30%), Escherichia coli (15%) and, Salmonella sp.(5%) in cattle whereas in buffalo showed that Clostridium perfringens (40%), Pasteurella multocida (25%), Escherichia coli (25%), Salmonella sp.(10%), A total of 42 isolates of Clostridium perfringens isolated from first and second group 12 isolates examined for type of toxin by using of Multiscreen Ag ELISA Enterotoxemia The main often occurring toxin type was type A (buffaloes: 5/50; cows: 7/50) Out of 14 isolates of E coli from first and second group examined samples were serologically positive to O111, 0104, O26, O113, O91,0103 and O126. PCR results showed that ten strains from 28 isolates, from the first and second group, were isolates and some of them have Kmt1, BlaROB1, and tetH genes. Antibiogram was applied upon the isolated bacterial pathogens and found that Ofloxacin - oxytetracycline - Aztreonam (Clostridium perfringens) Gentamycin, Ceftriaxone, and Norfloxacin (Pasteurella multocida) garamycin and oxytetracycline (Escherichia coli) and ciprofloxacin and ceftriaxone were the most effective antibiotic against salmonella sp. were the drug of choice for treatment of infected animals. [ABSTRACT FROM AUTHOR]

This study investigates the use of Moringa Leaf Powder (MLP) and Vitamin C in the diets of broiler chickens exposed to Aflatoxin B1 (AFB1) to enhance performance and health. Two hundred one-day old Cobb 500 broiler breed chicks were divided into four diet groups: CON (no AFB1, no MLP), AFB (0.2 mg AFB1 per kg of feed), AFV (0.2 mg AFB1 with 200 mg vitamin C), and AFM (0.2 mg AFB1 with 500 mg MLP). Supplementation with MLP and vitamin C led to improved broiler performance, with AFM and AFV groups exhibiting higher body weight gain, similar or lower feed intake, and better feed conversion ratios compared to AFB. Mortality rates were lower in AFM and AFV, and dressing percentages and liver weights were higher. Haematological parameters showed significant improvements in AFM and AFV compared to AFB. MLP and vitamin C reduced serum cholesterol levels and normalised liver enzymes. MLP improved kidney function. Using 200 mg kg-1 vitamin C or 500 mg kg-1 Moringa oleifera powder as dietary supplements for broiler chickens exposed to aflatoxin B1 is recommended for improved productivity and health.

Cypermethrin, a type II pyrethroid, is easily available over the counter, increasing the possibility of accidental and intentional exposures. Severe Cypermethrin exposure is rare but may lead to an organophosphate-like toxidrome, posing a diagnostic quandary to the critical care personnel. The authors present a case of a 25-year-old lady patient, who intentionally ingested a toxin or poison. On repeated investigation by medical personnel and family members, it eventually turned out to be cyperhit. On, immediate shifting to the Intensive Care Unit (ICU) following acute poisoning, her vital signs were more or less stable, but with mouth filled with copious mouth secretions and mild bronchorrhoea. An intravenous dose of 1.2 mg of atropine sulfate was administered because of bronchorrhoea, which led to satisfactory improvement, except for hypoglycaemia {(Random Blood Sugar(RBS): 67 mg/dL}. To address hypoglycaemia, an initial bolus of 25% dextrose (IV)/100 mL was injected followed by an infusion of 25% dextrose at a rate of 10 ml/hr. At the end of three days of close monitoring and psychiatric counseling sessions, she was fully alert, oriented, afebrile, and had stable vital signs. The present case suggests that Cypermethrin poisoning should be considered a differential diagnosis of patients presenting with classical features of organophosphorus poisoning. Inadvertent administration of pralidoxime and atropine can be avoided if emergency physicians are aware of this entity. Optimum Atropine administration is useful when the dose is adjusted as per the patient’s response.

La connaissance de l'anatomie permet non seulement un traitement optimum et donc une satisfaction pleine et entière de nos patientes, mais est aussi fondamentale dans la prévention des complications. Une compréhension approfondie du vieillissement permet de réaliser des traitements efficaces, car la plupart des patientes réclament un résultat naturel, supprimant les signes inévitables de l'âge, qui ne peuvent être compris qu'en prenant en compte leur vieillissement. Le vieillissement du visage est un processus naturel, mais multifactoriel complexe, plus particulièrement pour le front. Dans cet article, nous nous concentrerons sur la toxine botulique ainsi que les produits de comblement dans le cadre du vieillissement. Knowledge of anatomy not only allows optimal treatment and therefore full satisfaction of our patients, but is also fundamental in the prevention of complications. A thorough understanding of aging allows for effective treatments, as most patients demand a natural result, removing the inevitable signs of aging, which can only be understood by considering their aging. Facial aging is a natural but complex multifactorial process, particularly for the forehead. In this article, we will focus on botulinum toxin as well as fillers in aging. [ABSTRACT FROM AUTHOR]

The pine processionary moth Thaumetopoea wilkinsoni (Tams, 1926) (Lepidoptera: Notodontidae) is one of the most harmful species that causes destruction in pine ecosystems and also causes critical skin reactions in humans and animals due to its urticating hairs. This study aimed to evaluate the efficacy of different strains [Bti ATCC 35646 (wild-type strain), Bti pHT315, and Bti pHTppk (mutant strain)] of Diptera-targeted Bacillus thuringiensis subsp. israelensis (Bti) and toxins (spore/crystal mixtures) obtained from these strains against the 4th larval stage of T. wilkinsoni under laboratory conditions. T. wilkinsoni eggs were collected from pine trees at Ondokuz Mayıs University in Samsun, Turkey, in 2022. Pine needles were contaminated with bacterial strains of different concentrations (1 × 107, 1 × 108, 1 × 109 cfu/mL) in 5 mL and toxins in different concentrations (0.15, 0.3, 0.6, 1.25, 2.5, 5 mg/mL) in 2 mL. Larvae were placed in containers with 30 larvae in each group and were observed for 25 days. As a result of the study, Bti ATCC 35646 with 63.4% mortality and the lowest LC50 value of 1.2 × 109 cfu/mL among the three strains of Bti and Bti pHTppk with 76.7% mortality and the lowest LC50 value of 1.2 mL among the toxins from the Bti strains had found to be virulent for T. wilkinsoni. The results obtained from our study suggest that Diptera-targeted Bti is virulent to T. wilkinsoni and that this strain and spore/crystal mixture can be used in the biological control of this species. [ABSTRACT FROM AUTHOR]

Abstract Brown blotch disease in Agaricus bisporus reduces its commercial value, resulting in significant economic losses. The pathogens of brown blotch disease are diverse. Current research on the biological characteristics and toxins has been limited to Pseudomonas tolaasii but lacks understanding of other pathogens. Understanding the biological characteristics of the pathogens and identifying their toxins are essential prerequisites for disease prevention and control. This study isolated two pathogens from brown discoloration in A. bisporus in Guangxi, China, and identified them as Pseudomonas tolaasii and Cedecea neteri. C. neteri exhibited stronger resistance to sodium dodecyl sulfate (SDS) and H2O2 and a broader pH adaptation range than P. tolaasii. P. tolaasii showed higher swimming motility than C. neteri. C. neteri produces two toxins identified as phenylacetic acid and p-hydroxybenzoic acid, causing browning symptoms in A. bisporus at 20 μg and 10 μg, respectively. The present study compared various biological characteristics between P. tolaasii and C. neteri. The toxins produced by C. neteri were extracted and identified, and their toxicity to A. bisporus was evaluated, which is the first report on C. neteri toxins. These discoveries have enhanced our understanding of the biological characteristics and biotoxins of C. neteri. The research findings offer new insights for developing novel disease prevention and control strategies.

Escherichia coli strains producing the genotoxin colibactin, designated as CoPEC (colibactin-producing E. coli), have emerged as an important player in the etiology of colorectal cancer (CRC). Here, we investigated the role of macroautophagy/autophagy in myeloid cells, an important component of the tumor microenvironment, in the tumorigenesis of a susceptible mouse model infected with CoPEC. For that, a preclinical mouse model of CRC, the ApcMin/+ mice, with Atg16l1 deficiency specifically in myeloid cells (ApcMin/+/Atg16l1[∆MC]) and the corresponding control mice (ApcMin/+), were infected with a clinical CoPEC strain 11G5 or its isogenic mutant 11G5∆clbQ that does not produce colibactin. We showed that myeloid cell-specific Atg16l1 deficiency led to an increase in the volume of colonic tumors in ApcMin/+ mice under infection with 11G5, but not with 11G5∆clbQ. This was accompanied by increased colonocyte proliferation, enhanced inflammasome activation and IL1B/IL-1β secretion, increased neutrophil number and decreased total T cell and cytotoxic CD8+ T cell numbers in the colonic mucosa and tumors. In bone marrow-derived macrophages (BMDMs), compared to uninfected and 11G5∆clbQ-infected conditions, 11G5 infection increased inflammasome activation and IL1B secretion, and this was further enhanced by autophagy deficiency. These data indicate that ATG16L1 in myeloid cells was necessary to inhibit colonic tumor growth in CoPEC-infected ApcMin/+ mice via inhibiting colibactin-induced inflammasome activation and modulating immune cell response in the tumor microenvironment. Abbreviation: AOM, azoxymethane; APC, APC regulator of WNT signaling pathway; ATG, autophagy related; Atg16l1[∆MC] mice, mice deficient for Atg16l1 specifically in myeloid cells; CASP1, caspase 1; BMDM, bone marrow-derived macrophage; CFU, colony-forming unit; CoPEC, colibactin-producing Escherichia coli; CRC, colorectal cancer; CXCL1/KC, C-X-C motif chemokine ligand 1; ELISA, enzyme-linked immunosorbent assay; IL, interleukin; MC, myeloid cell; MOI, multiplicity of infection; PBS, phosphate-buffered saline; pks, polyketide synthase; qRT-PCR, quantitative real-time reverse-transcription polymerase chain reaction; siRNA, small interfering RNA; TME, tumor microenvironment; TNF/TNF-α, tumor necrosis factor. [ABSTRACT FROM AUTHOR]

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The sugarcane borer, Diatraea saccharalis, is one of the most important pests of sugarcane and corn crops in Argentina. In general, there are no control methods to manage this insect in the cane fields in the country. So, the development of borer resistance in sugarcane through transgenic technology could be the best approach, as in the case of Bt corn derived of the Bacillus thuringensis bacterium that has been the primary tool for managing this borer in the field. However, sugarcane borer control has been threatened by observations of resistance to certain varieties of Bt corn and the protein used in many new varieties. The susceptibility of two populations of sugarcane borer to different Bt toxins expressed in five genetically modified corns (two single and three pyramided genes) was determined for the development of a transgenic sugarcane. In laboratory bioassays, larval mortality of both populations on Bt corn leaf tissue containing Cry1F toxin was lower than other Bt technologies at 3 days of exposure. However, there were no significant differences between larval mortality of the five Bt corns at 7 days after infestation. In a greenhouse trial, larval survival and plant injury were not significant in Bt corns. The results suggest that any Bt protein could be incorporated into sugarcane crops for managing D. saccharalis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Botulinum neurotoxin (BoNT) is a substance used to treat chronic sialorrhea, muscle dystonia, and is used in cosmetic applications. Measuring the potency of BoNT is crucial because it acts even with a small amount. However, the current methods for measuring the potency of BoNT involve using two‐dimensional neuroblastoma cell line‐based methods. In this study, we aimed to develop a new method to measure the potency of BoNT using a three‐dimensional organoid culture system. Materials and Method: We established the optimal conditions for coculturing N2a neuronal cells with murine salivary gland organoids (SGOs). After determining the appropriate chemical concentrations, we treated the SGOs cocultured with N2a cells with BoNT type A (BoNT/A). We confirmed the expression of salivary gland‐related genes and proteins using real‐time polymerase chain reaction (PCR) and immunofluorescence staining. Results: The SGOs cocultured with N2a cells showed that the dendrites or axons of neuronal cells were in contact with the outermost layer of the SGOs. When we applied acetylcholine and neostigmine to the coculture systems, the mRNA expression of Aqp5 and Bhlha15, associated with salivary gland secretory cells, increased. However, this effect was reversed when BoNT/A was applied, as confirmed through real‐time PCR. Conclusion: We found that the coculture system of SGOs and N2a neuronal cells can potentially serve as a potency testing platform for BoNT. Level of Evidence: NA Laryngoscope, 134:2697–2704, 2024 [ABSTRACT FROM AUTHOR]

Among aquatic creatures, fish are the most diversified organisms that have emerged among other vertebrates. The objective of this research was to evaluate the anticancer properties of toxin extracts from the marine puffer fish Chelonodon patoca. The toxins were extracted from the samples by homogenizing with acetic acid, and the clear supernatant was subjected to anticancer activities by MTT for cytotoxicity and cell viability on both Vero and cancer cell lines (A-549, AGS, HT-29, and MDA-MB-231). More than 70% of the normal cells were viable up to 200 µg/ml of toxin extracts so that hence the concentration was fixed below 200 µg/ml for the cell viability study on human cancer cells. Among the various organs, the toxin extracted from the liver showed potential antiproliferative activity at an inhibitory concentration of 50 µg/ml on HT-29 and MDA-MB231cell lines, 75 µg/ml on A549 and 100 µg/ml on AGS. The cellular and nuclear morphological changes, induction of apoptosis, and its stages were observed microscopically through different staining methods. Further, the DNA damage was confirmed by DNA fragmentation analysis to confirm apoptosis. The results suggest that the extract of toxin (liver) shows a significant antiproliferative effect on the human cancer cell lines. [ABSTRACT FROM AUTHOR]

There is an urgent need for new nonantibiotic-based treatment strategies for Clostridioides difficile infection. C. difficile toxin B (TcdB) is a virulent factor that is essential for causing disease. Here, we investigated whether a survival-signaling pathway could protect against TcdB. We found significant increase in caspase-3 apoptotic activity in intestinal epithelial cells of mice exposed to TcdB. Subsequently, activation of the MIF-CD74-Akt prosurvival signaling pathway blocked TcdB-induced caspase-3 activity and intestinal epithelial cell death. This brief report provides proof-of-concept that targeting prosurvival pathways may represent a unique antibiotic-independent strategy for protecting against C. difficile toxin-mediated cell death. [ABSTRACT FROM AUTHOR]

The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development. [ABSTRACT FROM AUTHOR]

Copepods are a major component of metazooplankton and important prey for fish and invertebrates such as crabs, shrimps, and flatworms. Certain bloom-forming dinoflagellates can kill copepods, but there is little research on the interactions between copepods and the bloom-forming dinoflagellates Karenia bicuneiformis and K. selliformis. In this study, the survival and ingestion rates of the calanoid copepod Acartia hongi feeding on K. bicuneiformis and K. selliformis were determined as a function of prey concentration. On day 2, the survival of A. hongi incubated with K. bicuneiformis was 90–100% at all the tested prey concentrations, while that with K. selliformis was 0–20% at ≥ 582 ng C mL−1. Compared to other harmful dinoflagellates from the literature, K. bicuneiformis caused low mortality of Acartia; however, K. selliformis caused almost the highest mortality at similar dinoflagellate concentrations. With increasing mean prey concentration, the ingestion rates of A. hongi feeding on K. bicuneiformis increased on day 1, but those on K. selliformis did not increase. Acartia hongi stopped feeding on K. bicuneiformis at mean prey concentrations of ≥ 341 ng C mL−1 and K. selliformis at all prey concentrations on day 2. At the prey concentration of 1000 ng C mL−1, the ingestion rate of A. hongi feeding on K. bicuneiformis was moderate among the rates of Acartia spp. feeding on harmful dinoflagellates; however, that on K. selliformis was the lowest. These results indicate that K. bicuneiformis and K. selliformis differentially affect the survival and ingestion rates of A. hongi. [ABSTRACT FROM AUTHOR]

Gene duplication is a major force driving evolutionary innovation. A classic example is generating new animal toxins via duplication of physiological protein-encoding genes and recruitment into venom. While this process drives the innovation of many animal venoms, reverse recruitment of toxins into nonvenomous cells remains unresolved. Using comparative genomics, we find members of the Membrane Attack Complex and Perforin Family (MAC) have been recruited into venom-injecting cells (cnidocytes), in soft and stony corals and sea anemones, suggesting that the ancestral MAC was a cnidocyte expressed toxin. Further investigation into the model sea anemone Nematostella vectensis reveals that three members have undergone Nematostella -specific duplications leading to their reverse recruitment into endomesodermal cells. Furthermore, simultaneous knockdown of all three endomesodermally expressed MACs leads to mis-development, supporting that these paralogs have nonvenomous function. By resolving the evolutionary history and function of MACs in Nematostella , we provide the first proof for reverse recruitment from venom to organismal development. [ABSTRACT FROM AUTHOR]

We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues (3Asp, 25Lys, and 34Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3Glu, 25Arg, and 34Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts. [ABSTRACT FROM AUTHOR]

Brown blotch disease in Agaricus bisporus reduces its commercial value, resulting in significant economic losses. The pathogens of brown blotch disease are diverse. Current research on the biological characteristics and toxins has been limited to Pseudomonas tolaasii but lacks understanding of other pathogens. Understanding the biological characteristics of the pathogens and identifying their toxins are essential prerequisites for disease prevention and control. This study isolated two pathogens from brown discoloration in A. bisporus in Guangxi, China, and identified them as Pseudomonas tolaasii and Cedecea neteri. C. neteri exhibited stronger resistance to sodium dodecyl sulfate (SDS) and H2O2 and a broader pH adaptation range than P. tolaasii. P. tolaasii showed higher swimming motility than C. neteri. C. neteri produces two toxins identified as phenylacetic acid and p-hydroxybenzoic acid, causing browning symptoms in A. bisporus at 20 μg and 10 μg, respectively. The present study compared various biological characteristics between P. tolaasii and C. neteri. The toxins produced by C. neteri were extracted and identified, and their toxicity to A. bisporus was evaluated, which is the first report on C. neteri toxins. These discoveries have enhanced our understanding of the biological characteristics and biotoxins of C. neteri. The research findings offer new insights for developing novel disease prevention and control strategies. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a toxic mycotoxin produced by some mold species from genera Penicillium and Aspergillus. OTA has been detected in cereals, cereal-derived products, dried fruits, wine, grape juice, beer, tea, coffee, cocoa, nuts, spices, licorice, processed meat, cheese, and other foods. OTA can induce a wide range of health effects attributable to its toxicological properties, including teratogenicity, immunotoxicity, carcinogenicity, genotoxicity, neurotoxicity, and hepatotoxicity. OTA is not only toxic to humans but also harmful to livestock like cows, goats, and poultry. This is why the European Union and various countries regulate the maximum permitted levels of OTA in foods. This review intends to summarize all the main aspects concerning OTA, starting from the chemical structure and fungi that produce it, its presence in food, its toxicity, and methods of analysis, as well as control strategies, including both fungal development and methods of inactivation of the molecule. Finally, the review provides some ideas for future approaches aimed at reducing the OTA levels in foods. [ABSTRACT FROM AUTHOR]

Fenoxaprop-p-ethyl (FE) is one of the typical aryloxyphenoxypropionate herbicides. FE has been widely applied in agriculture in recent years. Human health and aquatic ecosystems are threatened by the cyanobacteria blooms caused by Microcystis aeruginosa, which is one of the most common cyanobacteria responsible for freshwater blooming. Few studies have been reported on the physiological effects of FE on M. aeruginosa. This study analyzed the growth curves, the contents of chlorophyll a and protein, the oxidative stress, and the microcystin-LR (MC-LR) levels of M. aeruginosa exposed to various FE concentrations (i.e., 0, 0.5, 1, 2, and 5 mg/L). FE was observed to stimulate the cell density, chlorophyll a content, and protein content of M. aeruginosa at 0.5- and 1-mg/L FE concentrations but inhibit them at 2 and 5 mg/L FE concentrations. The superoxide dismutase and catalase activities were enhanced and the malondialdehyde concentration was increased by FE. The intracellular (intra-) and extracellular (extra-) MC-LR contents were also affected by FE. The expression levels of photosynthesis-related genes psbD1, psaB, and rbcL varied in response to FE exposure. Moreover, the expressions of microcystin synthase-related genes mcyA and mcyD and microcystin transportation-related gene mcyH were significantly inhibited by the treatment with 2 and 5 mg/L FE concentrations. These results might be helpful in evaluating the ecotoxicity of FE and guiding the rational application of herbicides in modern agriculture. [ABSTRACT FROM AUTHOR]

The venom-containing barb attached to their 'whip-like' tail provides stingrays a defensive mechanism for evading predators such as sharks. From human encounters, dermal stingray envenomation is characterized by intense pain often followed by tissue necrosis occurring over several days to weeks. The bioactive components in stingray venoms (SRVs) and their molecular targets and mechanisms that mediate these complex responses are not well understood. Given the utility of venom-derived proteins from other venomous species for biomedical and pharmaceutical applications, we set out to characterize the bioactivity of SRV extracts from three local species that belong to the Dasyatoidea 'whiptail' superfamily. Multiple cell-based assays were used to quantify and compare the in vitro effects of these SRVs on different cell lines. All three SRVs demonstrated concentration-dependent growth-inhibitory effects on three different human cell lines tested. In contrast, a mouse fibrosarcoma cell line was markedly resistant to all three SRVs, indicating the molecular target(s) for mediating the SRV effects are not expressed on these cells. The multifunctional SRV responses were characterized by an acute disruption of cell adhesion leading to apoptosis. These findings aim to guide future investigations of individual SRV proteins and their molecular targets for potential use in biomedical applications. [ABSTRACT FROM AUTHOR]

Ribosome-inactivating proteins (RIPs) are a group of proteins with rRNA N-glycosylase activity that irreversibly inhibit protein synthesis and consequently cause cell death. Recently, an RIP called ledodin has been found in shiitake; it is cytotoxic, strongly inhibits protein synthesis, and shows rRNA N-glycosylase activity. In this work, we isolated and characterized a 50 kDa cytotoxic protein from shiitake that we named edodin. Edodin inhibits protein synthesis in a mammalian cell-free system, but not in insect-, yeast-, and bacteria-derived systems. It exhibits rRNA N-glycosylase and DNA-nicking activities, which relate it to plant RIPs. It was also shown to be toxic to HeLa and COLO 320 cells. Its structure is not related to other RIPs found in plants, bacteria, or fungi, but, instead, it presents the characteristic structure of the fold type I of pyridoxal phosphate-dependent enzymes. Homologous sequences have been found in other fungi of the class Agaricomycetes; thus, edodin could be a new type of toxin present in many fungi, some of them edible, which makes them of great interest in health, both for their involvement in food safety and for their potential biomedical and biotechnological applications. [ABSTRACT FROM AUTHOR]

This paper proposed a stochastic toxin-dependent competition model to investigate the impact of environmental noise on species interaction dynamics. First, a survival analysis was conducted to establish the sufficient conditions for population extinction and persistence. Second, we proved the existence of a unique ergodic stationary distribution. Finally, the spatial arrangement of random states near the deterministic attractor was investigated using the stochastic sensitivity functions technique. This analytical approach facilitates constructing confidence ellipses and estimating critical noise intensity corresponding to the onset of transition. Both theoretical and numerical findings demonstrated that significant levels of noise experienced by one species lead to its extinction while promoting persistence in its competitor; conversely, negligible levels of noise did not alter the original competition outcomes in the deterministic model. However, when both species encounter moderate levels of noise, various modifications can occur in competition outcomes. These findings have significant implications for preserving ecosystem diversity. [ABSTRACT FROM AUTHOR]

Nemertean worms contain toxins that are used to paralyze their prey and to deter potential predators. Hoplonemerteans often contain pyridyl alkaloids like anabaseine that act through nicotinic acetylcholine receptors and crustacean chemoreceptors. The chemical reactivity of anabaseine, the first nemertean alkaloid to be identified, has been exploited to make drug candidates selective for alpha7 subtype nAChRs. GTS-21, a drug candidate based on the anabaseine scaffold, has pro-cognitive and anti-inflammatory actions in animal models. The circumpolar chevron hoplonemertean Amphiporus angulatus contains a multitude of pyridyl compounds with neurotoxic, anti-feeding, and anti-fouling activities. Here, we report the isolation and structural identification of five new compounds, doubling the number of pyridyl alkaloids known to occur in this species. One compound is an isomer of the tobacco alkaloid anatabine, another is a unique dihydroisoquinoline, and three are analogs of the tetrapyridyl nemertelline. The structural characteristics of these ten compounds suggest several possible pathways for their biosynthesis. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims Klebsiella oxytoca (K. oxytoca) is the second bacterial cause of nosocomial infections in the general population after K. pneumoniae. This study surveyed the frequency of cytotoxin‐producing strains of K. oxytoca and their antibiotic susceptibility profile in a cohort of children admitted to a referral hospital with different malignancies. Methods The Stool samples of children admitted to the Cancer Chemotherapy Unit of the Mofid Children's Hospital, Tehran, Iran were analyzed using conventional biochemical tests and polymerase chain reaction targeting the pehX gene to identify K. oxytoca. The antibiotic susceptibility profile of isolated K. oxytoca against commonly prescribed antibiotics used in treating infection at the facility was determined using the Kirby–Bauer disk diffusion technique. Also, the prevalence of genes encoding toxins among K. oxytoca was identified by PCR assay. Results The Stool samples of 280 participants were taken for the study of which 38 samples [(55.3% (21/38) 42 males and 44.7% (17/38) females)] tested positive for various Klebsiella spp. Out of this, K. oxytoca was identified in 2.5% (7/280) stools using cultures and conventional biochemical tests. Also, the stools of 2.9% (8/280) of the participants tested positive for K. oxytoca using PCR assay. Using PCR, (2/7) of the K. oxytoca isolates tested positive for the npsA and npsB genes and were identified as toxigenic K. oxytoca strains. Conclusion The prevalence of toxin‐producing K. oxytoca strains in stool samples of children diagnosed with cancer in Iran is relatively low. Most of the K. oxytoca isolates were susceptible to tested antibiotics. Globally, active surveillance of toxigenic K. oxytoca strains in patients with different malignancies or immunocompromised patients is recommended in healthcare settings.

Successful colonization by the opportunistic pathogen Staphylococcus aureus depends on its ability to interact with other microorganisms. Staphylococcus aureus strains harbour a T7b subtype of type VII secretion system (T7SSb), a protein secretion system found in a wide variety of Bacillota, which functions in bacterial antagonism and virulence. Assessment of T7SSb activity in S. aureus has been hampered by low secretion activity under laboratory conditions and the lack of a sensitive assay to measure secretion. Here, we have utilized NanoLuc binary technology to develop a simple assay to monitor protein secretion via detection of bioluminescence. Fusion of the 11 amino acid NanoLuc fragment to the conserved substrate EsxA permits its extracellular detection upon supplementation with the large NanoLuc fragment and luciferase substrate. Following miniaturization of the assay to 384-well format, we use high-throughput analysis to demonstrate that T7SSb-dependent protein secretion differs across strains and growth temperature. We further show that the same assay can be used to monitor secretion of the surface-associated toxin substrate TspA. Using this approach, we identify three conserved accessory proteins required to mediate TspA secretion. Co-purification experiments confirm that all three proteins form a complex with TspA.

ABSTRACT Candida albicans causes millions of mucosal infections in humans annually. Hyphal overgrowth on mucosal surfaces is frequently associated with tissue damage caused by candidalysin, a secreted peptide toxin that destabilizes the plasma membrane of host cells thereby promoting disease and immunopathology. Candidalysin was first identified in C. albicans strain SC5314, but recent investigations have revealed candidalysin “variants” of differing amino acid sequence in isolates of C. albicans, and the related species C. dubliniensis, and C tropicalis, suggesting that sequence variation among candidalysins may be widespread in natural populations of these Candida species. Here, we analyzed ECE1 gene sequences from 182 C. albicans isolates, 10 C. dubliniensis isolates, and 78 C. tropicalis isolates and identified 10, 3, and 2 candidalysin variants in these species, respectively. Application of candidalysin variants to epithelial cells revealed differences in the ability to cause cellular damage, changes in metabolic activity, calcium influx, MAPK signalling, and cytokine secretion, while biophysical analyses indicated that variants exhibited differences in their ability to interact with and permeabilize a membrane. This study identifies candidalysin variants with differences in biological activity that are present in medically relevant Candida species.IMPORTANCEFungal infections are a significant burden to health. Candidalysin is a toxin produced by Candida albicans that damages host tissues, facilitating infection. Previously, we demonstrated that candidalysins exist in the related species C. dubliniensis and C. tropicalis, thereby identifying these molecules as a toxin family. Recent genomic analyses have highlighted the presence of a small number of candidalysin “variant” toxins, which have different amino acid sequences to those originally identified. Here, we screened genome sequences of isolates of C. albicans, C. dubliniensis, and C. tropicalis and identified candidalysin variants in all three species. When applied to epithelial cells, candidalysin variants differed in their ability to cause damage, activate intracellular signaling pathways, and induce innate immune responses, while biophysical analysis revealed differences in the ability of candidalysin variants to interact with lipid bilayers. These findings suggest that intraspecies variation in candidalysin amino acid sequence may influence fungal pathogenicity.

Current treatment of clostridial infections includes broad-spectrum antibiotics and antitoxins, yet antitoxins are ineffective against all Clostridiumspecies. Moreover, rising antimicrobial resistance (AMR) threatens treatment effectiveness and public health. This study therefore aimed to discover a common drug target for four pathogenic clostridial species, Clostridium botulinum, C. difficile, C. tetani, and C. perfringens through an in-silico core genomic approach. Using four reference genomes of C. botulinum, C. difficile, C. tetani, and C. perfringens, we identified 1484 core genomic proteins (371/genome) and screened them for potential drug targets. Through a subtractive approach, four core proteins were finally identified as drug targets, represented by type III pantothenate kinase (CoaX) and, selected for further analyses. Interestingly, the CoaX is involved in the phosphorylation of pantothenate (vitamin B5), which is a critical precursor for coenzyme A (CoA) biosynthesis. Investigation of druggability analysis on the identified drug target reinforces CoaX as a promising novel drug target for the selected Clostridium species. During the molecular screening of 1201 compounds, a known agonist drug compound (Vibegron) showed strong inhibitory activity against targeted clostridial CoaX. Additionally, we identified tazobactam, a beta-lactamase inhibitor, as effective against the newly proposed target, CoaX. Therefore, identifying CoaX as a single drug target effective against all four clostridial pathogens presents a valuable opportunity to develop a cost-effective treatment for multispecies clostridial infections.

Societal Impact Statement Gossypol and its derivatives represent a class of toxic and immunosuppressive compounds that are naturally synthesized in cottonseed. These compounds pose several health hazards to humans and animals, such as heart and lung damage, breathing difficulties, and death in swine. In poultry, gossypol reduces egg production and slows growth. Studies have also shown that gossypol can indirectly harm humans and animals through the food chain. Although several physical and chemical approaches are adopted to reduce gossypol levels in cottonseed before food and feed processing, these techniques are expensive. Therefore, genetically regulating gossypol production in cotton could provide a cheaper alternative. Summary Cotton (Gossypium spp.), the most important fiber crop, is cultivated in over a hundred countries to provide raw materials for the growing textile industry. The seed obtained after delinting cotton is a rich source of protein with a vast potential for oil and feed production. Cottonseed oil production is estimated at 5.08 million metric tons and is expected to generate over 6.56 billion United States Dollars in revenue by 2029. The cake from defatted cottonseed is used as animal feed and food supplements. However, the contamination of gossypol in cottonseed limits its use. Gossypol ingestion impairs weight gain and causes anorexia, respiratory distress, and death under extreme exposure. This review highlights the significance of cottonseed oil and meal; the pharmacological uses and impact of gossypol; the chemistry, toxicity, and bioactivity of gossypol; and the physical and chemical methods used in gossypol removal during feed and food supplement processing. In addition, the biosynthetic pathway of gossypol and attempts to genetically transform some key regulators of this pathway to produce glandless cottonseed or reduce the gossypol levels in the seed are discussed.