Novel Disperse Dyes Based on Enaminones: Synthesis, Dyeing Performance on Polyester Fabrics, and Potential Biological Activities.

1-(3-aryl)-3-(dimethylamino)prop-2-en-1-one (enaminones) derivatives and the diazonium salt of para-chloroaniline were used to synthesize several novel disperse azo dyes with high yield and the use of an environmentally friendly approach. At 100 and 130 °C, we dyed polyester fabrics using the new synthesized disperse dyes. At various temperatures, the dyed fabrics' color intensity was assessed. The results we obtained showed that dyeing utilizing a high temperature method at 130 °C was enhanced than dyeing utilizing a low temperature method at 100 °C. Reusing dye baths once or twice was a way to achieve two goals at the same time. The first was obtaining a dyed product at no cost, and the second was a way to treat the wastewater of dyeing bath effluents and reuse it again. Good results were obtained for the fastness characteristics of polyester dyed with disperse dyes. When the disperse dyes were tested against certain types of microbes and cancer cells, they demonstrated good and encouraging findings for the potential to be used as antioxidants and antimicrobial agents.

Stacked hybridization to enhance the performance of artificial neural networks (ANN) for prediction of water quality index in the Bagh river basin, India.

Water quality assessment is paramount for environmental monitoring and resource management, particularly in regions experiencing rapid urbanization and industrialization. This study introduces Artificial Neural Networks (ANN) and its hybrid machine learning models, namely ANN-RF (Random Forest), ANN-SVM (Support Vector Machine), ANN-RSS (Random Subspace), ANN-M5P (M5 Pruned), and ANN-AR (Additive Regression) for water quality assessment in the rapidly urbanizing and industrializing Bagh River Basin, India. The Relief algorithm was employed to select the most influential water quality input parameters, including Nitrate (NO3-), Magnesium (Mg2+), Sulphate (SO42-), Calcium (Ca2+), and Potassium (K+). The comparative analysis of developed ANN and its hybrid models was carried out using statistical indicators (i.e., Nash-Sutcliffe Efficiency (NSE), Pearson Correlation Coefficient (PCC), Coefficient of Determination (R2), Mean Absolute Error (MAE), Root Mean Square Error (RMSE), Relative Root Square Error (RRSE), Relative Absolute Error (RAE), and Mean Bias Error (MBE)) and graphical representations (i.e., Taylor diagram). Results indicate that the integration of support vector machine (SVM) with ANN significantly improves performance, yielding impressive statistical indicators: NSE (0.879), R2 (0.904), MAE (22.349), and MBE (12.548). The methodology outlined in this study can serve as a template for enhancing the predictive capabilities of ANN models in various other environmental and ecological applications, contributing to sustainable development and safeguarding natural resources.

Kikuchi-Fujimoto disease, simultaneously diagnosed with systemic lupus erythematosus in an Arabic female: an agonizing combination.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign condition affecting young Oriental-Asian females. It is characterized by fever and tender cervical lymphadenopathy with an unclear aetiology, and in most longitudinal reviews, KFD occurs before systemic lupus erythematosus (SLE). Herein, the case of a 28-year-old Kuwaiti female without any relevant past medical history, who was simultaneously diagnosed with KFD and SLE following an Ebstein-Barr virus infection, is reported. The patient was treated with oral prednisolone, hydroxychloroquine, cyclosporin, and belimumab and her response was clinically and biochemically favourable. Although KFD is prevalent in Asian populations, it may affect all races. Early diagnosis of KFD is difficult, particularly when simultaneously diagnosed with SLE, but crucial to preventing inappropriate therapy. Clinicians need to know about this rare disease, especially when patients present with fever and swollen lymph nodes, due to a risk of misdiagnosis with tuberculosis or lymphoma, as these are more often thought to be the cause of such symptoms.

Molecular Biomarkers and Signaling Pathways of Cancer Stem Cells in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequently found cancer in the world, and it is frequently discovered when it is already far along in its development. About 20% of cases of CRC are metastatic and incurable. There is more and more evidence that colorectal cancer stem cells (CCSCs), which are in charge of tumor growth, recurrence, and resistance to treatment, are what make CRC so different. Because we know more about stem cell biology, we quickly learned about the molecular processes and possible cross-talk between signaling pathways that affect the balance of cells in the gut and cancer. Wnt, Notch, TGF-ß, and Hedgehog are examples of signaling pathway members whose genes may change to produce CCSCs. These genes control self-renewal and pluripotency in SCs and then decide the function and phenotype of CCSCs. However, in terms of their ability to create tumors and susceptibility to chemotherapeutic drugs, CSCs differ from normal stem cells and the bulk of tumor cells. This may be the reason for the higher rate of cancer recurrence in patients who underwent both surgery and chemotherapy treatment. Scientists have found that a group of uncontrolled miRNAs related to CCSCs affect stemness properties. These miRNAs control CCSC functions like changing the expression of cell cycle genes, metastasis, and drug resistance mechanisms. CCSC-related miRNAs mostly control signal pathways that are known to be important for CCSC biology. The biomarkers (CD markers and miRNA) for CCSCs and their diagnostic roles are the main topics of this review study.

Significance of Scapular Fracture Existence in Blunt Chest Trauma: A Retrospective Cohort Study.

Background: Scapular fracture is a rare encounter in blunt trauma patients. The scapula is surrounded by strong groups of muscles offering good protection for the bone. Therefore, a high-energy trauma is needed to cause a scapular fracture. We aim to study scapular fractures and their relation to injury severity and mortality in blunt chest trauma (BCT) patients. Methods: We retrospectively collected data from all patients with BCT who were admitted to our hospital from December 2014 through January 2017. The injury details of all BCT patients were retrieved from the trauma registry of the hospital and were supplemented by patients' electronic files for missing information. Collected data included demography, mechanism of injury, vital signs, Glasgow Coma Score (GCS) on admission, injured body regions, management, Injury Severity Score (ISS), New Injury Severity Score (NISS), length of hospital stay (LOS), and mortality. Results: During the study period, 669 patients had BCT. Scapular fracture was present in 29 (4.3%) of the BCT patients. The scapular fracture was missed by chest X-ray in 35.7% of the patients; however, it was accurately diagnosed by computed tomography (CT) scan of the chest. Neck injury was significantly higher in patients with scapular fracture compared with patients without fracture (p < 0.001). ISS and NISS were significantly higher in patients with scapular fractures compared to other patients without fractures (p=0.04 and p=0.003 Mann-Whitney U test, respectively). Two patients with scapular fractures died due to severe associated injuries (the overall mortality was 9.6%). Conclusions: Scapular fracture in BCT patients indicates a high-energy type of trauma. Compared to a chest X-ray, CT scan was more accurate for the diagnosis of scapular fracture. Associated injuries are the main cause of trauma-related mortality rather than the direct effect of the fractured scapula. Particular attention and meticulous evaluation should be paid to head and neck injuries to avoid missing injuries.

Exploring the reproductive features of Clupisoma garua from Ganges River, Bangladesh: insights into eco-climatic factors for sustainable management and advancements in aquaculture practices.

The Garua bacha, Clupisoma garua, holds considerable commercial and nutritional significance as a fish species. This study investigates the relationships between GSI (gonadosomatic index) and eco-climatic conditions, and provides comprehensive insights into several facets of reproduction, such as size at first sexual maturity (Lm), spawning season, peak spawning period, and proposes sustainable management strategies for C. garua in the Ganges River, northwestern, Bangladesh. Since January to December 2017, 570 female individuals have been gathered from the Ganges River using cast nets, gill nets, and square lift nets on a monthly basis. The total length (TL) of the specimens varied from 3.90 to 26.30 cm. Lm was estimated as 14.30 cm based on the results of the TL vs. GSI, MGSI (modified gonadosomatic index), DI (Dobriyal index), 14.00 cm through TL-FL regressions, and 15.18 cm depending on Lmax for this species. Furthermore, the spawning period was observed from May to August, peaking in June and July, based on greater GSI, MGSI, and DI values. Throughout the peak spawning season, there was not a significant differ from a value of 100 in the relative weight (WR) of the female species. During the spawning season, a substantial association between temperature and GSI (p = 0.0038); rainfall and GSI (p = 0.0043); DO and GSI (p = 0.0043); pH and GSI (p = 0.0002); and alkalinity and GSI (p = 0.0001) was detected. Analyzing a 55-year data series (1964-2018), it became clear that an increase in average air temperature of 0.0289 °C and a decrease in rainfall of 2.988 mm per year might possibly delay the spawning season of this species. As a consequence, the results of this study provide crucial information for developing management strategies to safeguard C. garua populations in the Ganges River and its adjacent ecosystems.

Development and characterization of three novel mouse monoclonal antibodies targeting spike protein S1 subunit of Middle East Respiratory Syndrome Corona Virus.

BACKGROUND: Middle East Respiratory Syndrome Coronavirus is a highly pathogenic virus that poses a significant threat to public health. OBJECTIVE: The purpose of this study is to develop and characterize novel mouse monoclonal antibodies targeting the spike protein S1 subunit of the Middle East Respiratory Syndrome Corona Virus (MERS-CoV). METHODS: In this study, three mouse monoclonal antibodies (mAbs) against MERS-CoV were generated and characterized using hybridoma technology. The mAbs were evaluated for their reactivity and neutralization activity. The mAbs were generated through hybridoma technology by the fusion of myeloma cells and spleen cells from MERS-CoV-S1 immunized mice. The resulting hybridomas were screened for antibody production using enzyme-linked immunosorbent assays (ELISA). RESULTS: ELISA results demonstrated that all three mAbs exhibited strong reactivity against the MERS-CoV S1-antigen. Similarly, dot-ELISA revealed their ability to specifically recognize viral components, indicating their potential for diagnostic applications. Under non-denaturing conditions, Western blot showed the mAbs to have robust reactivity against a specific band at 116 KDa, corresponding to a putative MERS-CoV S1-antigen. However, no reactive bands were observed under denaturing conditions, suggesting that the antibodies recognize conformational epitopes. The neutralization assay showed no in vitro reactivity against MERS-CoV. CONCLUSION: This study successfully generated three mouse monoclonal antibodies against MERS-CoV using hybridoma technology. The antibodies exhibited strong reactivity against MERS-CoV antigens using ELISA and dot ELISA assays. Taken together, these findings highlight the significance of these mAbs for potential use as valuable tools for MERS-CoV research and diagnosis (community and field-based surveillance and viral antigen detection).

Unveiling the tyrosinase inhibitory potential of phenolics from Centaurium spicatum: Bridging in silico and in vitro perspectives.

Phenolics, abundant in plants, constitute a significant portion of phytoconstituents consumed in the human diet. The phytochemical screening of the aerial parts of Centaurium spicatum led to the isolation of five phenolics. The anti-tyrosinase activities of the isolated compounds were assessed through a combination of in vitro experiments and multiple in silico approaches. Docking and molecular dynamics (MD) simulation techniques were utilized to figure out the binding interactions of the isolated phytochemicals with tyrosinase. The findings from molecular docking analysis revealed that the isolated phenolics were able to bind effectively to tyrosinase and potentially inhibit substrate binding, consequently diminishing the catalytic activity of tyrosinase. Among isolated compounds, cichoric acid displayed the lowest binding energy and the highest extent of polar interactions with the target enzyme. Analysis of MD simulation trajectories indicated that equilibrium was reached within 30 ns for all complexes of tyrosinase with the isolated phenolics. Among the five ligands studied, cichoric acid exhibited the lowest interaction energies, rendering its complex with tyrosinase the most stable. Considering these collective findings, cichoric acid emerges as a promising candidate for the design and development of a potential tyrosinase inhibitor. Furthermore, the in vitro anti-tyrosinase activity assay unveiled significant variations among the isolated compounds. Notably, cichoric acid exhibited the most potent inhibitory effect, as evidenced by the lowest IC50 value (7.92 ± 1.32 µg/ml), followed by isorhamnetin and gentiopicrin. In contrast, sinapic acid demonstrated the least inhibitory activity against tyrosinase, with the highest IC50 value. Moreover, cichoric acid exhibited a mixed inhibition mode against the hydrolysis of l-DOPA catalyzed by tyrosinase, with Ki value of 1.64. Remarkably, these experimental findings align well with the outcomes of docking and MD simulations, underscoring the consistency and reliability of our computational predictions with the actual inhibitory potential observed in vitro.

Extracorporeal Femoro-Carotid Shunt for Transcarotid Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement may be performed with a transcarotid approach when peripheral vascular disease is prohibitive for transfemoral access. In this case, a patient who presented in cardiogenic shock secondary to severe aortic stenosis developed electroencephalographic changes during transcarotid TAVR. A temporary extracorporeal femoro-carotid shunt permitted successful TAVR.

A novel layered double hydroxide-based ternary nanocomposite for the effective photocatalytic degradation of rhodamine B.

Photocatalytic degradation of organic pollutants is a green and effective route of wastewater treatment. Zinc oxide was initially used for this purpose; however, calcined zinc/chromium layered double hydroxide (ZnCr-LDO) and cadmium sulfide quantum dots (CdSQDs)-based nanocomposites proved as superior alternatives. Herein, we report a green sonochemical method for the sol-gel fabrication of novel CdSQDs@ZnCr-LDO/ZnO ternary nanocomposite that exhibited exceptional photocatalytic activity for the degradation of rhodamine B dye (RhB), in wastewaters, under UV-A-irradiation. The features of the ternary nanocomposite were investigated using various physicochemical techniques, including XRD, SEM, TEM, EDX, XPS, BET, zeta potential, DRS, and PL measurements. The RhB dye % removal was 38.02, 40.2, and 98% using pristine ZnO, ZnCr-LDO and the ternary CdSQDs@ZnCr-LDO/ZnO-based nanomaterials, respectively, reflecting the superior ternary nanocomposite's photocatalytic activity that made it an excellent competitor to commonly reported photocatalysts. Additionally, an investigation was carried out to determine the key reactive species in the photocatalytic degradation of RhB, considering both scavenger's type and concentration. The prevailing mechanism was found to be the reductive photodegradation pathway. Furthermore, several models were utilized to describe the kinetics of photocatalytic performance of the ternary nanocomposite and a typical Z-scheme type-II photocatalytic heterojunction mechanism was inferred.

Association between hepatitis C virus genotype 4 and renal cell carcinoma: Molecular and virological studies.

Hepatitis C virus (HCV) is the most common infection worldwide. The correlation between HCV and renal cell carcinoma (RCC) is still mysterious. Therefore, the relationship between HCV and RCC was investigated. The study included 100 patients with RCC; 32 with HCV infection, and 68 without HCV infection. Expressions of viral proteins (NS3 and NS5A) were tested using an immune electron-microscope (IEM) and immunohistochemistry (IHC). IHC and quantitative real time-PCR investigated the presentation of human proteins TP53 and p21 genes. Transmission electron (TEM) detected viral-like particles in infected RCC tissues. The gene and protein expression of P53 was higher in HCV positive versus HCV negative patients and p21 was lower in HCV positive versus HCV negative in both tumor and normal tissue samples. Viral like particles were observed by TEM in the infected tumor and normal portion of the RCC tissues and the plasma samples. The IEM showed the depositions of NS3 and NS5A in infected renal tissues, while in noninfected samples, were not observed. The study hypothesizes that a correlation between HCV and RCC could exist through successfully detecting HCV-like particles, HCV proteins, and (p53 and p21) in RCC-infected patients.

Automatic brain-tumor diagnosis using cascaded deep convolutional neural networks with symmetric U-Net and asymmetric residual-blocks.

The use of various kinds of magnetic resonance imaging (MRI) techniques for examining brain tissue has increased significantly in recent years, and manual investigation of each of the resulting images can be a time-consuming task. This paper presents an automatic brain-tumor diagnosis system that uses a CNN for detection, classification, and segmentation of glioblastomas; the latter stage seeks to segment tumors inside glioma MRI images. The structure of the developed multi-unit system consists of two stages. The first stage is responsible for tumor detection and classification by categorizing brain MRI images into normal, high-grade glioma (glioblastoma), and low-grade glioma. The uniqueness of the proposed network lies in its use of different levels of features, including local and global paths. The second stage is responsible for tumor segmentation, and skip connections and residual units are used during this step. Using 1800 images extracted from the BraTS 2017 dataset, the detection and classification stage was found to achieve a maximum accuracy of 99%. The segmentation stage was then evaluated using the Dice score, specificity, and sensitivity. The results showed that the suggested deep-learning-based system ranks highest among a variety of different strategies reported in the literature.

Smart chitosan nanogel for targeted doxorubicin delivery, ensuring precise release, and minimizing side effects in Ehrlich ascites carcinoma-bearing mice.

In recent decades, bio-polymeric nanogels have become a forefront in medical research as innovative in-vivo drug carriers. This study introduces a pH-sensitive chitosan nanoparticles/P(N-Isopropylacrylamide-co-Acrylic acid) nanogel (CSNPs/P(NIPAm-co-AAc)), making significant advancements. The nanogel effectively encapsulated doxorubicin hydrochloride (Dx. HCl), a model drug, within its compartments through electrostatic binding. Comparing nano chitosan (CSNPs) before and after integrating copolymerized P(NIPAm-co-AAc), highlighting an improved and adaptable nanogel structure with responsive behaviors. The intraperitoneal delivery of Dx-loaded nanogel (Dx@N.gel) to Ehrlich ascites carcinoma (Eh)-bearing mice at doses equivalent to 1.5 and 3 mg/kg of Dx per day for 14 days exhibited superiority over the administration of free Dx. Dx@N.gel demonstrated heightened anticancer activity, significantly improving mean survival rates in Eh mice. The nanogel's multifaceted defense mechanism mitigated oxidative stress, inhibited lipid peroxidation, and curbed nitric oxide formation induced by free Dx. It effectively countered hepatic DNA deterioration, normalized elevated liver and cardiac enzyme levels, and ameliorated renal complications. This pH-responsive CSNPs/P(NIPAm-co-AAc) nanogel loaded with Dx represents a paradigm shift in antitumor drug delivery. Its efficacy and ability to minimize side effects, contrasting sharply with those of free Dx, offer a promising future where potent cancer therapies seamlessly align with patient well-being.

Comparison between stem cell therapy and stem cell derived exosomes on induced multiple sclerosis in dogs.

BACKGROUND: Multiple sclerosis (MS) is a chronic condition that primarily manifests as demyelination of neuronal axons in the central nervous system, due to the loss or attack of oligodendroglia cells that form myelin. Stem cell therapy has shown promising results for the treatment of MS due to its capability to halt the immune attack, stop apoptosis and axonal degeneration, and differentiate into oligodendrocytes. Stem cell-derived Exosomes (Exosomes) have shown great capabilities for neuronal diseases as they have growth factors, complex sets of miRNA, enzymes, proteins, major peptides, lipids, and macromolecules with anti-inflammatory, angiogenesis, and neurogenesis activities. METHODS: This study aimed to compare the healing properties of stem cells, against Exosomes for the treatment of an experimentally induced MS dog model. Dog models of MS received either a single treatment of stem cells or a single treatment of Exosomes intrathecally and the treatment process was evaluated clinically, radiologically, histopathologically, and electron microscopy and cerebrospinal fluid analysis. RESULTS: showed marked amelioration of the clinical signs in both treated groups compared to the control one, magnetic resonance scans showed the resolution of the hyperintense lesions at the end of the study period, the histopathology and electron microscopy showed marked healing properties and remyelination in treated groups with superiority of the stem cells compared to Exosomes. CONCLUSIONS: Although stem cell results were superior to Exosomes therapy; Exosomes have proven to be effective and safe important actors in myelin regeneration, and their use in diseases like MS helps to stimulate remyelination.

Long-standing Nonunited Fracture Lateral Humeral Condyle in Children. Evaluating a Two-stage Surgical Treatment Strategy With Critical Review.

OBJECTIVE: This work aimed to evaluate the results of using a 2-stage surgical treatment strategy without doing anterior transposition of the ulnar nerve (ATUN) for cases with long-standing nonunited fracture lateral humeral condyle (LHC) in children, accompanied by a critical review. METHODS: A consecutive 12 children with a long-standing ">2 years" nonunited LHC with evident radiologic gross anatomic distortion of the elbow were included in this study. A 2-stage surgical treatment strategy was applied, wherein the first stage, open functional reduction, osteosynthesis, and iliac bone graft were done. Then after 6 months, the second stage surgery was carried out in the form of supracondylar humeral corrective osteotomy if the cubitus valgus angle was ≥20 degrees. ATUN was not done for any of the cases even with those having ulnar nerve dysfunction. RESULTS: Union took place in 11 out of the 12 cases after a mean follow-up period of 11 weeks (range: 8 to 14 wk; SD: 1.6). All the 7 cases showed preoperative ulnar nerve dysfunction and reported clinical recovery at the end of their follow-up. CONCLUSIONS: Two-stage surgical treatment strategy without ATUN is a convenient, reproducible, and successful line of treatment for children presented with longstanding nonunited LHC with anatomically distorted elbow. LEVEL OF EVIDENCE: Level IV-case series.

Effect of silica fume substitution by limestone powder and cement kiln dust on the shrinkage, durability, and sustainability of UHPC.

Silica fume is usually used in UHPC, three times more than that for normal concrete, to enhance mechanical properties and durability. However, silica fume (SF) is an expensive material and has high production costs. This work is aimed at investigating the shrinkage and durability performance of previously developed UHPC mixtures utilizing the two calcareous waste materials, namely limestone powder (LSP) and cement kiln dust (CKD), by partially replacing the silica fume. The optimally selected mixtures of UHPC, having flow and strength above the minimum required, were used for detailed investigation in terms of shrinkage and durability characteristics. The results showed that by replacing SF with up to 20% of LSP and up to 20% of CKD, the mechanical properties of UHPC remained satisfactory compared to the control mixture with 100% SF. However, the ultimate shrinkage was higher for mixtures incorporating LSP or CKD, indicating the need for more volume of steel fibers to compensate for the shrinkage strains. The developed UHPCs also exhibited high resistance against reinforcement corrosion and sulfate attack, making them suitable for use in aggressive exposure conditions. However, special attention needs to be paid to the CKD content, where it is recommended to limit the content of CKD to about 15% or less to control the durability performance of the UHPCs. In addition, the sustainability analysis of developed UHPC mixtures was carried out using the life-cycle assessment and eco-strength intensity index. The results indicated that the UHPC mixtures possess a higher life-cycle and are therefore more sustainable.

Tackling access and payer barriers for growth hormone therapy in Saudi Arabia: a consensus statement for the Saudi Working Group for Pediatric Endocrinology.

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

New imidazole-2-thiones linked to acenaphythylenone as dual DNA intercalators and topoisomerase II inhibitors: structural optimization, docking, and apoptosis studies.

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.

Phenotypic and genotypic characterization of resistance and virulence in Pseudomonas aeruginosa isolated from poultry farms in Egypt using whole genome sequencing.

Pseudomonas aeruginosa (P. aeruginosa) is an ESKAPE pathogen that can quickly develop resistance to most antibiotics. This bacterium is a zoonotic pathogen that can be found in humans, animals, foods, and environmental samples, making it a One-Health concern. P. aeruginosa threatens the poultry industry in Egypt, leading to significant economic losses. However, the investigation of this bacterium using NGS technology is nearly non-existent in Egypt. In this study, 38 isolates obtained from broiler farms of the Delta region were phenotypically investigated, and their genomes were characterized using whole genome sequencing (WGS). The study found that 100% of the isolates were resistant to fosfomycin and harbored the fosA gene. They were also resistant to trimethoprim/sulfamethoxazole, although only one isolate harbored the sul1 gene. Non-susceptibility (resistant, susceptible with increased dose) of colistin was observed in all isolates. WGS analysis revealed a high level of diversity between isolates, and MLST analysis allocated the 38 P. aeruginosa isolates into 11 distinct sequence types. The most predominant sequence type was ST267, found in 13 isolates, followed by ST1395 in 8 isolates. The isolates were susceptible to almost all tested antibiotics carrying only few different antimicrobial resistance (AMR) genes. Various AMR genes that confer resistance mainly to ß-lactam, aminoglycoside, sulfonamide, and phenicol compounds were identified. Additionally, several virulence associated genes were found without any significant differences in number and distribution among isolates. The majority of the virulence genes was identified in almost all isolates. The fact that P. aeruginosa, which harbors several AMR and virulence-associated factors, is present in poultry farms is alarming and threatens public health. The misuse of antimicrobial compounds in poultry farms plays a significant role in resistance development. Thus, increasing awareness and implementing strict veterinary regulations to guide the use of veterinary antibiotics is required to reduce health and environmental risks. Further studies from a One-Health perspective using WGS are necessary to trace the potential transmission routes of resistance between animals and humans and clarify resistance mechanisms.