POLE Mutation Spectra Are Shaped by the Mutant Allele Identity, Its Abundance, and Mismatch Repair Status.

Human tumors with exonuclease domain mutations in the gene encoding DNA polymerase ε (POLE) have incredibly high mutation burdens. These errors arise in four unique mutation signatures occurring in different relative amounts, the etiologies of which remain poorly understood. We used CRISPR-Cas9 to engineer human cell lines expressing POLE tumor variants, with and without mismatch repair (MMR). Whole-exome sequencing of these cells after defined numbers of population doublings permitted analysis of nascent mutation accumulation. Unlike an exonuclease active site mutant that we previously characterized, POLE cancer mutants readily drive signature mutagenesis in the presence of functional MMR. Comparison of cell line and human patient data suggests that the relative abundance of mutation signatures partitions POLE tumors into distinct subgroups dependent on the nature of the POLE allele, its expression level, and MMR status. These results suggest that different POLE mutants have previously unappreciated differences in replication fidelity and mutagenesis.

Effect of polystyrene nanoplastics exposure on gene expression and pathogenesis of zoonotic pathogen, Edwardsiella piscicida.

A surge in the number of anthropogenic pollutants has been caused by increasing industrial activities. Nanoplastics are spotlighted as a new aquatic pollutant that are a threat to microbes and larger organisms. Our previous study showed that the subinhibitory concentrations of aquatic pollutants such as phenol and formalin act as signaling molecules and modulate global gene expression and metabolism. In this study, we aimed to investigate the impact of a new type of anthropogenic contaminant, polystyrene (PS) nanoplastics, on the expression of key virulence factors in zoonotic pathogen Edwardsiella piscicida and the assessment of potential changes in the susceptibility of zebrafish as a model host. The TEM data indicated a noticeable change in the cell membrane indicating that PS particles were possibly entering the bacterial cells. Transcriptome analyses performed to identify the differentially expressed genes upon PS exposure revealed that the genes involved in major virulence factor type VI secretion system (T6SS) were down-regulated. However, the expression of T6SS-related genes was recovered from the PS adapted E. piscicida when nanoplastics are free. This demonstrated the hypervirulence of pathogen in infection assays with both cell lines and in vivo zebrafish model. Therefore, this study provides experimental evidence elucidating the direct regulatory impact of nanoplastics influx into aquatic ecosystems on fish pathogenic bacteria, notably influencing the expression of virulence factors.

The efficiency of technologies used for epidemiological characterization of Listeria monocytogenes isolates: an update.

The characterization of pathogenic bacteria by providing information regarding the identification and source-tracking of the causes of outbreaks is vital for the epidemiological investigations of foodborne diseases. The knowledge of transmission of Listeria monocytogenes (L. monocytogenes) strains from the environment, directly or indirectly (through food processing facilities) to the final food products, due to the complexity of evaluating numerous, affecting parameters is quite limited. The food trade globalization also adds difficulties in tracking the association between the infection occurrence and causative pathogens, aiming to prevent their spread. The occurrence of listeriosis, a notifiable disease throughout the world, can either be sporadic or outbreak-related. Due to the importance of foodborne outbreaks from a public health aspect and its correspondence enormous economic losses, cross-linked surveillance studies regarding the contamination of foods by L. monocytogenes, besides identifying clusters and tracing the sources of infections on an international-scale to prevent and control L. monocytogenes outbreaks sounds very crucial. Contrary to the conventional typing methods, molecular-based techniques, such as whole-genome sequencing, owing to the capacity to discriminate L. monocytogenes strains down to single nucleotide differences, provide an accurate characterization of strains and tracking the causes of outbreaks. However, routinely using molecular-based methods depends on the required improvements in the affordability, proper timing, and preparing reliable, standardized bioinformatics facilities. This work was conducted to critically review the practical potential of diverse typing methods have been used for the characterization of L. monocytogenes and discuss how they might change the future of efforts for control of listeriosis.

Design and Synthesis of Acridine-Triazole and Acridine-Thiadiazole Derivatives and Their Inhibitory Effect against Cancer Cells.

We report herein the design and synthesis of a series of novel acridine-triazole and acridine-thiadiazole derivatives. The newly synthesized compounds and the key intermediates were all evaluated for their antitumor activities against human foreskin fibroblasts (HFF), human gastric cancer cells-803 (MGC-803), hepatocellular carcinoma bel-7404 (BEL-7404), large cell lung cancer cells (NCI-H460), and bladder cancer cells (T24). Most of the compounds exhibited high levels of antitumor activity against MGC-803 and T24 but low toxicity against human normal liver cells (LO2), and their effect was even better than the commercial anticancer drugs, 5-fluorouracil (5-FU) and cis-platinum. Further, pharmacological mechanisms such as topo I, cell cycle, cell apoptosis, and neovascularization were all evaluated. Only a few compounds exhibited potent topo I inhibitory activity at 100 µM. In addition, the most active compounds with an IC50 value of 5.52-8.93 µM were chosen, and they could induce cell apoptosis in the G2 stage of MGC-803 or mainly arrest T24 cells in the S stage. To our delight, most of the compounds exhibited lower zebrafish cytotoxicity but could strongly inhibit the formation of zebrafish sub-intestinal veins, indicating a potential for clinical application.

Micro/nanoencapsulation strategy to improve the efficiency of natural antimicrobials against Listeria monocytogenes in food products.

Listeria monocytogenes (Lm), the etiological agent of listeriosis diseases in humans, is a serious pathogenic microorganism threatening the food safety especially in ready-to-eat food products. Adhesion on both biotic and abiotic surfaces is making it a potential source of contamination by Lm. Also, this bacterium has become more tolerant in food processing conditions, including in the presence of adverse conditions such as cold and dehydration. One of the attractive and effective methods to inhibit the growth of Lm in the food products is using natural antimicrobial agents, which can be a suitable alternative to synthetic preservatives for producing organic food products. The use of pure natural antimicrobials has some limitations including low stability against harsh conditions, low solubility and absorption, and un-controlled release, which can decrease their functions. These limitations have been overcome by using new advanced encapsulation techniques, which have boosted the anti-listerial activity of natural agents. Therefore, the current paper is aiming to review the results of recent studies conducted on using natural antimicrobials added directly or as encapsulated forms into the food formulation to control the growth of Lm. The information of current study can be used by the researchers as well as the food companies for the optimization of food formulations through encapsulation strategies to control Lm and potentially produce safe foods for the consumers.

Molecular Design, Synthesis and Docking Study of Alkyl and Benzyl Derivatives of Robustic Acid as Topoisomerase I Inhibitors.

Robustic acid is reported to be a bioactive compound, isolated from the medicinal plant Dalbergia benthamii Prain. Ten alkyl and benzyl derivatives (2a-2j) of robustic acid were designed and synthesized based on molecular docking approaches. The biological activities of most of the synthesized compounds (such as 2g, 2h, and 2i) were closely consistent with the docking results. In particular, 4-O-phenylpropyl substituted compound 2g displayed potent topoisomerase I inhibitory activity as well as cytotoxicity against SMMC-7721, HepG2, and HeLa cell lines. Further biological testing suggests that compound 2g acted mainly by an arrest of the tumor cells in G1 phase of the cell cycle and suppressed cell proliferation by inducing apoptosis. The findings of this study are encouraging with respect to potential utilization of these compounds as new topoisomerase I inhibitors.

Sorrel Extract Reduces Oxidant Production in Airway Epithelial Cells Exposed to Swine Barn Dust Extract In Vitro.

Exposure to hog barn organic dust contributes to occupational lung diseases, which are mediated by inflammatory and oxidative stress pathways. Isoprostanes-a family of eicosanoids produced by oxidation of phospholipids by oxygen radicals-are biomarkers of pulmonary oxidative stress. Importantly, 8-isoprostane has been implicated as a key biomarker and mediator of oxidative stress because it is a potent pulmonary vasoconstrictor. Antioxidants found in fruits and vegetables hold promise for preventing or reducing effects of oxidative stress-related diseases including chronic bronchitis and chronic obstructive pulmonary disease (COPD). Here, we investigated 8-isoP and oxidant production by organic dust-exposed airway epithelial cells and the inhibitory effects of an extract from calyces of the sorrel plant, Hibiscus sabdariffa, on oxidant-producing pathways. Confluent cultures of normal human tracheobronchial epithelial cells were pretreated or not with 1% sorrel extract prior to 5% dust extract (DE) exposure. Following DE treatments, live cells, cell-free supernatants, or cell extracts were evaluated for the presence of 8-isoprostane, superoxide, hydrogen peroxide, nitric oxide, hydroxyl radical, peroxynitrite, and catalase activity to evaluate sorrel's inhibitory effect on oxidative stress. The well-known radical scavenging antioxidant, N-acetyl cysteine (NAC), was used for comparisons with sorrel. DE exposure augmented the production of all radicals measured including 8-isoprostane (p value < 0.001), which could be inhibited by NAC or sorrel. Among reactive oxygen and nitrogen species generated in response to DE exposure, sorrel had no effect on H2O2 production and NAC had no significant effect on NO· production. The observations reported here suggest a possible role for sorrel in preventing 8-isoprostane and oxidant-mediated stress responses in bronchial epithelial cells exposed to hog barn dust. These findings suggest a potential role for oxidative stress pathways in mediating occupational lung diseases and antioxidants within sorrel and NAC in reducing dust-mediated oxidative stress within the airways of exposed workers.

Synthesis and Evaluation of Anticancer Activity of New 4-Acyloxy Derivatives of Robustic Acid.

In the present study, a series of 4-acyloxy robustic acid derivatives were synthesized and characterized for evaluation of their anti-cancer activity. The structures of these derivatives were elucidated by mass spectra (MS) nuclear magnetic resonance spectra (NMR). The single-crystal X-ray diffraction structure of one of these compounds was obtained, for further validation of the target compound structures. The anticancer activities of the target products were evaluated against human leukemic cells HL-60, human non-small cell lung carcinoma cells A-549, human hepatic carcinoma cells SMMC-7721, human hepatocellular carcinoma cells HepG2, and human cervical carcinoma cells Hela. Three compounds among them exhibited potent in-vitro cytotoxicity and excellent DNA topoisomerase I inhibitory activity, even at 0.1 mM concentrations. The most noteworthy observation was the minor toxicity of two of these compounds to normal cells, with an activity similar to the positive control in cancerous cells. A Surflex-Dock docking study was performed to investigate the topoisomerase I activity of all compounds. Of all the other compounds, the most sensitive compound was selected for further investigation of its effect on apoptosis induction and cell cycle regulation in HL-60 cells. Our results suggest that the anticancer effects of these compounds can be attributed to their pharmacological effects on topoisomerase I, cell apoptosis, and cell cycle. These findings suggest that robustic acid derivatives could be used as potential antitumor drugs.

Design, Synthesis, Antimicrobial, and Anticancer Activities of Acridine Thiosemicarbazides Derivatives.

Background: Acridine and thiourea derivatives are important compounds in medicinal chemistry due to their diverse biological properties including anticancer and antimicrobial effects. However, literature reveals some side effects associated with use of acridines. It is suggested that hybrid molecules may reduce the side effects and enhance the beneficial properties due to synergistic activity. The objectives of the present study are to synthesize and evaluate the anticancer and antimicrobial properties of new hybrids of acridine thiosemicarbazides derivatives. Results: The structures of the synthesized compounds 4a-4e were elucidated by MS and NMR spectra. In antimicrobial assay, Compound 4c exhibited potent antimicrobial activity compared to the other four compounds. In anticancer studies, we observed that compounds 4a, 4b, 4d and 4e exhibited high cytotoxicity against the MT-4 cell line, with IC50 values of 18.42 ± 1.18, 15.73 ± 0.90, 10.96 ± 0.62 and 11.63 ± 0.11 µM, respectively. The evaluation of anticancer effects, and the associated mechanism reveals that, the anticancer activities may be related to Topo I inhibitory activity, apoptosis and cell-cycle. Molecular docking studies revealed that the presence of planar naphtho-fused rings and a flexible thiourea group together, could improve DNA-intercalation and inhibition of DNA-Topo I activity. Conclusions: The results of this study demonstrate that the rational design of target derivatives as novel antimicrobial or antitumor leads is feasible.

Effect of Pelargonidin isolated from Ficus benghalensis L. on phenotypic changes in zebrafish (Danio rerio) embryos.

In the present study, the extraction and isolation of Pelargonidin, an anthocyanin compound from stem bark of Ficus benghalensis are described. The study also involves evaluation of the effect of Pelargonidin on phenotypic variations in zebra fish embryos. Extraction and isolation of Pelargonidin were carried out by employing liquid-liquid extraction technique, phytochemical tests, column chromatography, UV and FT-IR. In the zebra fish embryo model, Paclitaxel was employed as a negative control. A series of phenotypic changes in different stages of embryonic development were studied with treatment concentrations of Pelargonidin between 3.0 and 20 ppm at 0-72-hour post-fertilization (hpf). The results of our studies indicate that, after exposure of zebra fish embryos to 3.3-20 ppm concentration of Pelargonidin for 72 h, a significant reduction in aortic development occurs. At the dose level of 0.5 ppm Paclitaxel and Pelargonidin in the dose range between 3.3 and 20 ppm, the zebra fish embryos were found to have bent tail, malformed eyes and developmental delays in vasculature. Based on the results obtained, we infer that Pelargonidin can exhibit phenotypic anti-angiogenic variations in embryonic stage of fish embryos and it can be applied in future for exploration of its anti-angiogenic potential. Furthermore, Pelargonidin could serve as a candidate drug for in vivo inhibition of angiogenesis and can be applied for the treatment of neovascular diseases and tumor.

Acute toxicity profiling of the ethyl acetate fraction of Swietenia macrophylla seeds and in-vitro neuroprotection studies.

Swietenia macrophylla (SM) is a medicinally important plant found in tropical and subtropical regions of the world. The ethyl acetate fraction of the seeds of S. macrophylla (SMEAF) is reported to exhibit potent anticancer, antitumor, anti-inflammatory and antifeedant activities. Till date, there have been no studies reported on the acute oral toxicity profile of the ethyl acetate fraction of the seeds of SM. The objective of the present study was to determine the acute toxicity of SMEAF and evaluate the in-vitro neuroprotective activity of SMEAF using primary neuronal cell cultures. In acute oral toxicity study, the SMEAF did not produce any lethal signs of morbidity and mortality. Histo-pathological findings, support the safety of SMEAF, as there were no significant changes observed in any of the parameters studied. Based on the results obtained in MTT assay, we infer that SMEAF has a significant neuroprotective effect, as it increased the cell viability and exhibited protection to the neuronal cells against TBHP induced oxidative stress. Thus, SMEAF can be suggested for use in the development of herbal drug formulations with neuroprotective potential.

Effects of Antibiotic Residues on Fish Gut Microbiome Dysbiosis and Mucosal Barrier-Related Pathogen Susceptibility in Zebrafish Experimental Model.

The symbiotic community of microorganisms in the gut plays an important role in the health of the host. While many previous studies have been performed on the interactions between the gut microbiome and the host in mammals, studies in fish are still lacking. In this study, we investigated changes in the intestinal microbiome and pathogen susceptibility of zebrafish (Danio rerio) following chronic antibiotics exposure. The chronic antibiotics exposure assay was performed on zebrafish for 30 days using oxytetracycline (Otc), sulfamethoxazole/trimethoprim (Smx/Tmp), or erythromycin (Ery), which are antibiotics widely used in the aquaculture industry. The microbiome analysis indicated that Fusobacteria, Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla in the gut microbiome of the zebrafish used in this study. However, in Smx/Tmp-treated zebrafish, the compositions of Fusobacteria and Proteobacteria were changed significantly, and in Ery-treated zebrafish, the compositions of Proteobacteria and Firmicutes were altered significantly. Although alpha diversity analysis showed that there was no significant difference in the richness, beta diversity analysis revealed a community imbalance in the gut microbiome of all chronically antibiotics-exposed zebrafish. Intriguingly, in zebrafish with dysbiosis in the gut microbiome, the pathogen susceptibility to Edwardsiella piscicida, a representative Gram-negative fish pathogen, was reduced. Gut microbiome imbalance resulted in a higher count of goblet cells in intestinal tissue and an upregulation of genes related to the intestinal mucosal barrier. In addition, as innate immunity was enhanced by the increased mucosal barrier, immune and stress-related gene expression in the intestinal tissue was downregulated. In this study, we provide new insight into the effect of gut microbiome dysbiosis on pathogen susceptibility.

Spray-Dried Plasma Promotes Broiler Chick Growth by Enhancing Immune Surveillance.

Spray-dried plasma (SDP) contain a variety of functional proteins that play an immunomodulatory role. To evaluate the potential of SDP to stimulate the immune system, day-old Ross 708 male broiler chicks (200) were allocated randomly to five dietary treatments. Treatment 1 (CX) comprised chicks fed basal unmedicated corn-soybean meal (SBM) without the addition of SDP. Treatment 2 (MX) includes chicks fed unmedicated corn-SBM basal containing Bacitracin methylene disalicylate (BMD) at 0.055 g/kg diet. Treatments 3 (SDP1), 4 (SDP2), and 5 (SDP3) contained chicks given unmedicated corn-SBM basal, into which SDP was included at 10, 20, and 30 g/kg diet, respectively. On d 7, 14, and 21, chicks' body weight and FCR were calculated. Additionally, leucocyte counts, oxidative status, and IgY concentrations were determined in blood. On d 23, fecal populations of selected indicator bacteria species were determined. Results showed that FCR for SP3 was superior (p < 0.05) to other treatments. Likewise, heterophil numbers decreased in MX and SDP treatments compared to CX. Circulating IgY concentration was higher for SDP dietary treatments (p < 0.05) compared to MX. In conclusion, dietary SDP at 30 g/kg enhanced immune surveillance by increasing circulating IgY levels, maintaining a normal oxidative state, and increasing gut Bifidobacteria, thereby improving chick growth performance.

Interaction of Tau with Kinesin-1: Effect of Kinesin-1 Heavy Chain Elimination on Autophagy-Mediated Mutant Tau Degradation.

Natively unfolded tau has a low propensity to form aggregates, but in tauopathies, such as Alzheimer's disease (AD), tau aggregates into paired helical filaments (PHFs) and neurofibrillary tangles (NFTs). Multiple intracellular transport pathways utilize kinesin-1, a plus-end-directed microtubule-based motor. Kinesin-1 is crucial in various neurodegenerative diseases as it transports multiple cargoes along the microtubules (MT). Kinesin-1 proteins cannot progress along MTs due to an accumulation of tau on their surfaces. Although kinesin-1-mediated neuronal transport dysfunction is well-documented in other neurodegenerative diseases, its role in AD has received less attention. Very recently, we have shown that knocking down and knocking out of kinesin-1 heavy chain (KIF5B KO) expression significantly reduced the level and stability of tau in cells and tau transgenic mice, respectively. Here, we report that tau interacts with the motor domain of KIF5B in vivo and in vitro, possibly through its microtubule-binding repeat domain. This interaction leads to the inhibition of the ATPase activity of the motor domain. In addition, the KIF5B KO results in autophagy initiation, which subsequently assists in tau degradation. The mechanisms behind KIF5B KO-mediated tau degradation seem to involve its interaction with tau, promoting the trafficking of tau through retrograde transport into autophagosomes for subsequent lysosomal degradation of tau. Our results suggest how KIF5B removal facilitates the movement of autophagosomes toward lysosomes for efficient tau degradation. This mechanism can be enabled through the downregulation of kinesin-1 or the disruption of the association between kinesin-1 and tau, particularly in cases when neurons perceive disturbances in intercellular axonal transport.

Antimicrobial susceptibility testing of Shiga toxin-producing Escherichia coli from various samples by using a spiral gradient endpoint technique.

Shiga toxin-producing Escherichia coli (STEC) remains a major public health concern. Microbial resistance may be due to use of antimicrobial agents (AAs) as a growth promoter in food animals or overuse of AAs in humans. The objective of the current study was to determine the antimicrobial susceptibility patterns of STEC strains isolated from food, veterinary, and clinical sources against 14 AAs by using the spiral gradient endpoint method. One hundred ten isolates from three sources were characterized. Results of the current study showed that all strains were resistant to the folate pathway inhibiting AAs including tylosin tartrate (gradient minimum inhibitory concentration [GMIC] ranges from ≥180.00 to 256.00 µg/mL; end concentration [EC] ranges from ≥130.00 to 151.22 µg/mL; and tail-end concentration [TEC] ≥145.00 µg/mL). All the strains isolated from three sources were susceptible to the fluoroquinolone class of AAs (GMIC ranges from ≤1.00 to 64.30 µg/mL; EC ranges from ≤3.33 to 72.00 µg/mL; and TEC ranges from ≤12.13 to 45.00 µg/mL). Among the food isolates, less resistance was found within the aminoglycoside and amphenicol group (GMIC ≥256.00 µg/mL; EC=161.00 µg/mL). Eight strains were resistant to one to three, 44 strains were resistant to four to six, and two strains were resistant to seven or more AAs. All the clinical isolates (100%) were susceptible to the fluoroquinolones and gentamycin. Results also showed that antimicrobial resistance was observed between four and six AAs among the isolates. Some veterinary isolates were resistant to five AAs. Least AAs resistance was shown by 3.7% of isolates to gentamycin and 7.45% to chloramphenicol. This study showed an increasing trend of antimicrobial resistant strains of STEC, and we suggest that periodic surveillance of the antimicrobial susceptibility may be a useful measure to detect the antimicrobial resistant pathogens.

Saudi Arabia Household Awareness and Knowledge of Food Safety.

Food safety is a critical problem that impacts everyone worldwide. Many countries around the world are becoming increasingly reliant on the availability and safety of their food supply. Despite growing public consciousness about food-related dangers, the growth in food poisoning cases implies that individuals continue to make food consumption, food storage, and food preparation decisions that are less than optimal from a health and safety standpoint. The aim of this study was to assess Saudi Arabia's households' knowledge and practices of food safety. A cross-sectional study was conducted to assess knowledge of food safety and practices among a group of households in Saudi Arabia. An online questionnaire using social media (Facebook, Twitter, Instagram, and WhatsApp), and emails communications were distributed. A total of 309 adults (age range 18-59 years) participated in the study. In general, there were no differences between regions regarding the knowledge of food safety. Additionally, most of the participants had good practices of food safety. The findings of our study show that the gender, age, and educational level are factors that have an impact on the knowledge of food safety among respondents. Regarding food safety practices, in general, the results show that the participants had good practices. Therefore, organizations should focus on educational programs, training, holding workshops and activities in public places such as malls, schools, and home visit to improve and increases food safety knowledge and practices.

The Association of Toxoplasma gondii IgG and Liver Injury in US Adults.

BACKGROUND: Toxoplasma gondii (T. gondii) is a ubiquitous obligatory intracellular parasite which infects over 40 million Americans and causes toxoplasmosis. Inside the human body, T. gondii can damage tissues and invade vital organs. METHODS: This study evaluated the association of T. gondii infection and liver disease using data from the National Health and Nutrition Examination Survey (NHANES) 2009-2010, with a sample size of 3371 participants (age 20-80 years). Toxoplasma infection was determined by the level of T. gondii IgG antibody in serum samples. Liver disease was assessed by liver injury biomarkers and the Fatty Liver Index (US-FLI). The evaluation of the association between T. gondii infection and liver disease included the calculation of the Mantel-Haenszel risk ratio (RRMH), Rho-Scott chi-square bivariate analyses, design-based t-tests, and linear and logistic regression models which were adjusted for demographic and anthropometric covariates. RESULTS: Mean levels of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly more elevated in the T. gondii IgG-positive (IgG+) participants as compared to T. gondii-negative (IgG-) participants, p = 0.0435 and 0.0310, respectively. In linear regression analysis, exposure to T. gondii IgG+ had statistically significant positive associations with AST (p = 0.0211), alanine aminotransferase (ALT) (p = 0.0221), and gamma-glutamyl transferase (GGT) (p = 0.0258) after adjusting for BMI, age, gender, and race. T. gondii exposure was associated with an elevated relative risk of chronic liver disease (CLD) (RRMH = 1.26, 95% CI: 1.05-1.51). This association was more pronounced in certain occupations, such as construction, agriculture, forestry, and fishing, where Toxoplasma infection is more common (p = 0.0477). Moreover, Toxoplasma infection increased the odds of nonalcoholic fatty liver disease (NAFLD) (OR = 6.99, 95% CI = 1.85-26.32, p = 0.0237). CONCLUSION: T. gondii IgG+ antibody was significantly associated with liver injury biomarkers (ALT, AST, GGT, and ALP) and an increased risk of CLD and NAFLD. Moreover, the association of Toxoplasma with CLD was more evident in specific occupations where the prevalence of Toxoplasma was high. The findings of this study provide insight into utilizing liver biomarkers and US-FLI to assess the health complications of Toxoplasma when imaging tests are not accessible.

Preparation and Release of pH-Sensitive ß-Cyclodextrin Derivative Micelles Loaded with Paclitaxel.

In this paper, a new amphiphilic mono-6-ß-cyclodextrin octadecylimine (6-ß-CD-N-ODMA) copolymer was synthesized based on ß-cyclodextrin and octadecylamine, which can self-assemble to form polymeric micelles. Drug-loaded micelles (a new drug carrier) were obtained using 6-ß-CD-N-ODMA and paclitaxel (PTX) by the dialysis method. Orthogonal experiments were used to optimize the preparation method of the drug-loaded micelles. The drug-loading content of the carrier prepared by the optimized method was 1.97%. The physicochemical properties of blank micelles and drug-loaded micelles were evaluated by the fluorescence probe method, infrared spectra, dynamic light scattering, and scanning electron microscopy. The release properties of the carrier were investigated. The carrier has good pH sensitivity and the cumulative release rate after 96 h was 88% in PBS (pH = 5.0). The Ritger-Peppas equation is the optimal model for PTX released at pH 5.0, implying that the hydrolysis effect of 6-ß-CD-N-ODMA is the main reason for PTX release. The results indicate that the developed carrier can increase the solubility of PTX and possess potential for increased clinical efficacy of PTX.

Targeting foodborne pathogens via surface-functionalized nano-antimicrobials.

The incorporation of antibiotics and bioactive compounds into non-toxic nanoparticles has been popularly used to produce effective antimicrobial nanocarriers against foodborne pathogens. These systems can protect antimicrobials against harsh environments, control their release, and increase their antimicrobial activities; however, their functions can be decreased by some major barriers. Intracellular localization of bacteria protects them from the host immune system and antimicrobial agents. Also, bacteria can cause constant infection by nestling in professional phagocytic cells. In the last years, surface functionalization of nanocarriers by passive and active modification methods has been applied for their protection against clearance from the blood, increasing both circulation time and uptake by target cells. For achieving this objective, different functional agents such as specifically targeted peptides internalize ligands, saccharide ligands, or even therapeutic molecules (e.g., antibodies or enzymes) are used. In this review, techniques for functionalizing the surface of antimicrobial-loaded nanocarriers have been described. This article offers a comprehensive review of the potential of functional nanoparticles to increase the performance of antimicrobials against foodborne pathogens through targeting delivery.

Foliar Application of Different Iron Sources Improves Morpho-Physiological Traits and Nutritional Quality of Broad Bean Grown in Sandy Soil.

Nano-fertilizers are a new tool that can be used to address plant production challenges, and it addresses such nutrient deficiencies through smart agriculture approaches. Iron (Fe) is a vital element for several metabolic and physiological processes; however, Fe deficiency is common in poorly fertile soils (sand soil) and in arid areas. Therefore, additional research is required to select the most efficient form of iron absorbance. This research was implemented on broad bean plants (Vicia faba L. var. major Harz) to examine the impact of three iron sources: nano-iron (FeNPs, T1), iron sulfate (T2), and chelated iron (T3) as a foliar spray on the morphological properties, physiological attributes, and nutritional status of these plants compared to the untreated plants (control). The obtained results showed that foliar spraying with FeNPs, chelated iron and sulphate iron fertilizers increased plant height by 35.01%, 26.2, and 20.4%; leaf area by 38.8%, 18.3%, and 8.1%; the fresh weight of the plant by 47%, 32.8%, and 7.3%; the dry weight of the plant by 52.9%, 37.3%, and 11.2%; and the number of branches by 47%, 31.3%, and 25.6 %, respectively, compared to the control treatment (CT). Furthermore, the application of FeNPs, chelated iron, and sulphate iron fertilizers improved the number of pods by 47.9%, 24.8%, and 6.1%; the number of seeds by 32.8%, 7.9%, and 2.8%; and seed weight by 20.8%, 9.1%, and 5.4%, compared to control treatment (CT). Additionally, foliar application of FeNPs showed the highest values of photosynthesis rate (Pn), water-use efficiency (WUE), total chlorophyll, and phytohormones (IAA, GA3) compared to all the other treatments. The anatomical structure revealed an enhancement of leaf size and thickness (epidermis cells and mesophyll tissue) affected by FeNPs treatment compared to other treatments. Foliar application of FeNPs also improved the total content of carbohydrates, crude protein, element content (N, P, K, Ca, Na, Fe, Zn, Mn, and Cu), and some amino acids such as lysine, arginine, phenylalanine, isoleucine, and tyrosine in the seeds of broad beans. Based on the above results, the maximum values of all tested measurements were observed when FeNPs were used as the foliar spraying followed by chelated and sulphate iron fertilizers. Therefore, these findings suggest that using FeNPs, as a foliar treatment, could be a promising strategy for reducing the Fe deficiency in sandy soil and enhancing plant growth, pod yield, and pod quality of broad bean plants in addition to being environmentally favored in arid areas.