In this study, a sustainable and eco-friendly method was used to prepare zinc oxide nanoparticles (ZnO-NPs) using a sea cucumber aqueous extract. Then, ZnO-NPs were characterized by instrumental analysis (UV-vis, HR-TEM, XRD, FT-IR, and DLS) and evaluated for their possible antibacterial, antifungal, and insecticidal activities. Additionally, the toxicity of ZnO-NPs was evaluated in vivo against Nile Tilapia (Oreochromis niloticus). The sea cucumber was collected from the Gulf of Suez (Red Sea) at Al-Ain Al-Sokhna coast in Egypt and identified as Holothuria impatiens. The prepared Hi-ZnO-NPs peaked at 350 nm in UV–Vis spectral analysis. They showed quasi-spherical shaped particles with sizes ranging from 13 nm to 47 nm and a predominate size of 26 nm as indicated by HR-TEM. The XRD pattern of Hi-ZnO-NPs revealed a crystalline phase with an average size of 17.2 nm as calculated by Debye–Scherrer equation. FTIR analysis revealed the possible role of H. impatiens biological molecules in the biosynthesis process of ZnO-NPs. Hi-ZnO-NPs showed a negative zeta potential of −19.6 mV, demonstrating moderate stability. Biosynthesized Hi-ZnO-NPs revealed broad antimicrobial activity against Gram-positive bacteria (S. aureus ATCC 25923 and E. feacalis), Gram-negative bacteria (S. typhi, K. pneumonia and E. coli), and filamentous fungi (Aspergillus niger). Hi-ZnO-NPs demonstrated larvicidal activity against the mosquito, Culex pipiens (LC₅₀ = 2.756 ppm and LC₉₀ = 9.294 ppm), and adulticidal action against the housefly, Musca domestica (LD₅₀ = 4.285 ppm and LD₉₀ = 22.847 ppm). Interestingly, Hi-ZnO-NPs did not show mortality effects against Nile tilapia fish (Oreochromis niloticus), highlighting the potential safety of Hi-ZnO-NPs to highly exposed, non-target organisms. However, histopathological and hematological investigations provided dose-dependent impacts of Hi-ZnO-NPs to Nile tilapia. Overall, data provide an eco-friendly approach for synthesizing novel Hi-ZnO-NPs with multiple biomedical properties and potentially low toxicity to Nile tilapia fish.

Head and neck squamous cell carcinomas (HNSCCs) are a common type of cancer, ranking as the sixth most prevalent cancer worldwide and having a high morbidity and mortality rate. Among oropharyngeal squamous cell carcinoma (OPSCC) cancers, tonsillar squamous cell carcinoma (TSCC) is the most prevalent and has a particularly aggressive clinical course with poor disease outcomes. The tumor microenvironment (TME) of HNSCC is complex and heterogeneous, playing a crucial role in effective cancer therapy. Understanding the interaction between cancer inflammation, immunity, oncogenes, and tumor suppressor genes is essential for developing effective cancer treatments. This study aimed to gain a comprehensive understanding of the transcriptomes of the TME in TSCC, both associated with human papillomavirus (HPV) and not associated with HPV. The gene expression profiles of 168 genes linked to various cellular mediators and factors involved in inflammation, immunity crosstalk, transcription, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis were analyzed. We identified 40 differentially expressed genes related to the communication between tumor cells and the cellular mediators of inflammation and immunity crosstalk. In HPV-positive TSCC patients, 33 genes were over-expressed with a fold change greater than 1.5, and 26 of these genes were unique to this group. In contrast, HPV-negative TSCC patients had 11 up-regulated genes. The results further showed that 48 gene transcripts related to oncogenesis, tumor suppression, angiogenesis, and apoptosis were up-regulated in both HPV-positive and HPV-negative TSCC patients. Among the HPV-positive TSCC patients, 37 genes were over-expressed, while the HPV-negative TSCC patients had 11 up-regulated genes. The tumor microenvironment (TME) of HPV-associated and HPV-non-associated TSCC exhibited distinct characteristics, including the dysregulation of various genes involved in cellular mediators, inflammation, immunity crosstalk, transcription factors, immune signaling pathways, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. Additionally, we detected six Hr-HPV genotypes in 81% of the TSCC patients, with HPV-16 and HPV-35 being the most common types, followed by HPV-45 and HPV-18. HPV-39 and 31 were also identified. The presence of Hr-HPV genotypes in TSCC patients varied from single to multiple infections. In conclusion, we observed distinct heterogeneity in the transcriptome of the microenvironment in HPV-associated and non-associated TSCC. Further in vitro and in vivo studies are needed to investigate the functional implications of the identified over-expressed genes. Also, deeper molecular pathways and immunological studies on the TME are required to determine the potential of targeting genes for cancer therapy.

The marine environment is a rich source of bioactive compounds. Therefore, the sea cucumber was isolated from the Red Sea at the Al-Ain Al-Sokhna coast and it was identified as surf redfish (Actinopyga mauritiana). The aqueous extract of the surf redfish was utilized as an ecofriendly, novel and sustainable approach to fabricate zinc oxide nanoparticles (ZnO-NPs). The biosynthesized ZnO-NPs were physico-chemically characterized and evaluated for their possible antibacterial and insecticidal activities. Additionally, their safety in the non-target organism model (Nile tilapia fish) was also investigated. ZnO-NPs were spherical with an average size of 24.69 ± 11.61 nm and had a peak at 350 nm as shown by TEM and UV-Vis, respectively. XRD analysis indicated a crystalline phase of ZnO-NPs with an average size of 21.7 nm. The FTIR pattern showed biological residues from the surf redfish extract, highlighting their potential role in the biosynthesis process. DLS indicated a negative zeta potential (−19.2 mV) of the ZnO-NPs which is a good preliminary indicator for their stability. ZnO-NPs showed larvicidal activity against mosquito Culex pipiens (LC₅₀ = 15.412 ppm and LC₉₀ = 52.745 ppm) and a potent adulticidal effect to the housefly Musca domestica (LD₅₀ = 21.132 ppm and LD₉₀ = 84.930 ppm). Tested concentrations of ZnO-NPs showed strong activity against the 3rd larval instar. Topical assays revealed dose-dependent adulticidal activity against M. domestica after 24 h of treatment with ZnO-NPs. ZnO-NPs presented a wide antibacterial activity against two fish-pathogen bacteria, Pseudomonas aeruginosa and Aeromonas hydrophila. Histopathological and hematological investigations of the non-target organism, Nile tilapia fish exposed to 75–600 ppm ZnO-NPs provide dose-dependent impacts. Overall, data highlighted the potential applications of surf redfish-mediated ZnO-NPs as an effective and safe way to control mosquitoes, houseflies and fish pathogenic bacteria.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a major cause of bloodstream infections and poses serious challenges to clinical management because treatment options are limited. This study aimed to characterize antimicrobial resistance, virulence-associated features, and molecular epidemiology of CRKP bloodstream isolates using integrated phenotypic and genomic approaches. A total of 74 non-duplicate CRKP isolates were collected from bloodstream infections at three tertiary-care hospitals in Riyadh, Saudi Arabia, between 2022 and 2024. All isolates showed classical Klebsiella pneumoniae phenotypic characteristics, including intrinsic resistance to natural and aminopenicillins, and were classified as either multidrug-resistant (MDR) or extensively drug-resistant (XDR). Resistance to imipenem was universal, and resistance to other β-lactams and fluoroquinolones was high. Carbapenemase genes were detected in 96.0% of isolates using the GeneXpert^® Carba-R assay, with bla_OXA-48-like and bla_NDM being most common. Whole-genome sequencing demonstrated predominance of Ambler class D carbapenemases, particularly bla_OXA-232, with additional contributions from bla_NDM-1 and bla_NDM-5. Co-occurrence of carbapenemase genes was observed in a subset of isolates. Virulence analysis showed that 37.8% of isolates exhibited a hypermucoviscous phenotype, and more than half carried at least one virulence-associated determinant linked to capsule regulation or iron acquisition. In contrast, most isolates showed weak or no biofilm-forming capacity. Multilocus sequence typing revealed substantial genetic diversity but clear dominance of high-risk lineages, particularly ST147 and the emerging ST2096, both closely associated with bla_OXA-232 and bla_OXA-48-like genes. Capsular and O-antigen analysis showed a non-random distribution dominated by KL64 and O1/O2. Phylogenetic analysis was consistent with clonal expansion and suggested intra-hospital spread, with the intensive care unit serving as a key reservoir and dissemination to other wards. In conclusion, CRKP bloodstream infections in this setting are largely associated with a limited number of epidemic clones that combine extensive antimicrobial resistance with virulence-associated traits. These findings support the need for ongoing genome-based surveillance, strengthened infection control measures, and antimicrobial stewardship to limit the spread of high-risk K. pneumoniae lineages in healthcare settings.

Background Because of increase in drug resistance and a scarcity of effective treatment options, tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health threat. In the realm of TB drug discovery, the enzyme decaprenylphosphoryl-β-D-ribose oxidase (DprE1) serves as a validated and essential therapeutic target. This research primarily focusses on the in-silico development of novel 3-Methyl-3 H-naphtho[1,2,3-de]quinoline-2,7-dione derivatives as potential DprE1 inhibitors. Methodology A structure-based drug design strategy was employed to identify robust candidates, incorporating pharmacokinetic analyses, molecular docking, and molecular dynamics (MD) simulations. The molecular docking study revealed strong binding interactions of the proposed derivatives within the DprE1 active site, highlighting essential hydrogen bonds and hydrophobic interactions that facilitate target inhibition. Results MD simulations (250 ns) were performed to assess the stability, flexibility, and conformational dynamics of protein-ligand complexes, thereby validating docking results. Stable binding was indicated by critical metrics such as root mean square deviation (RMSD) and root mean square fluctuation (RMSF). Binding free energy calculations (MM/PBSA) quantified the favourable thermodynamics of ligand binding. Additionally, the drug-like properties of the top candidates were confirmed through ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) predictions, ensuring favourable pharmacokinetic and safety profiles. Several optimised compounds of 3-Methyl-3 H-naphtho[1,2,3-de]quinoline-2,7-dione with significant potential as tuberculosis inhibitors were identified through these in silico methodologies. Conclusion These compounds have been predicted to bind strongly to DprE1, demonstrating excellent specificity and antitubercular action. and offer a foundation for subsequent experimental validation.

Microsporum gypseum is a dermatophyte with a geophilic nature that is found all over the globe. It mainly causes tinea in the scalp, arms, and legs in humans. Squalene epoxidase (SE) is a crucial enzyme in M. gypseum for the biosynthesis of ergosterol. The medicinal plant Balanites aegyptiaca is an abundant supply of secondary constituents with great therapeutic values. In this research, the fruit epicarp portion was used to inhibit M. gypseum using experimental and computational techniques. The anti-dermatophytic activity of epicarp extracts on M. gypseum was evaluated using the poison plate method at five different concentrations. At 3 mg/mL, the M. gypseum was completely controlled by the fractioned chloroform extract of epicarp. The compounds from previous research were utilized for docking studies (Abuthakir et al., 2022). The ideal compounds and the drug terbinafine were then docked using Schrödinger’s Glide module. It demonstrates that (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside outperforms other substances and the drug terbinafine in docking analysis. Desmond, Schrödinger Molecular Dynamics simulations were also performed for (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside-squalene epoxidase complexes. The complex appears to be more stable, according to the MD simulation research. This study indicates that (3E)-7-Hydroxy-3,7-dimethyl-3-octen-1-yl-6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside could be used as a potential inhibitor of M. gypseum growth, and it could be studied further.