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Background Natural antimicrobial agents such as nisin were used to control the growth of foodborne pathogens in dairy products. The current study aimed to examine the inhibitory effect of pure nisin and nisin nanoparticles (nisin NPs) against methicillin resistant Staphylococcus aureus (MRSA) and E.coli O157:H7 during the manufacturing and storage of yoghurt. Nisin NPs were prepared using new, natural, and safe nano-precipitation method by acetic acid. The prepared NPs were characterized using zeta-sizer and transmission electron microscopy (TEM). In addition, the cytotoxicity of nisin NPs on vero cells was assessed using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The minimum inhibitory concentrations (MICs) of nisin and its nanoparticles were determined using agar well-diffusion method. Further, fresh buffalo’s milk was inoculated with MRSA or E.coli O157:H7 (1 × 10 6 CFU/ml) with the addition of either nisin or nisin NPs, and then the inoculated milk was used for yoghurt making. The organoleptic properties, pH and bacterial load of the obtained yoghurt were evaluated during storage in comparison to control group. Results The obtained results showed a strong antibacterial activity of nisin NPs (0.125 mg/mL) against MRSA and E.coli O157:H7 in comparison with control and pure nisin groups. Notably, complete eradication of MRSA and E.coli O157:H7 was observed in yoghurt formulated with nisin NPs after 24 h and 5th day of storage, respectively. The shelf life of yoghurt inoculated with nisin nanoparticles was extended than those manufactured without addition of such nanoparticles. Conclusions Overall, the present study indicated that the addition of nisin NPs during processing of yoghurt could be a useful tool for food preservation against MRSA and E.coli O157:H7 in dairy industry.

The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft tissues for healing and pain control following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were formulated and assessed for their hydration capacity, mucoadhesion ability and in vitro release profile to select the optimum system for further clinical investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10% glycerol showed optimum properties and was selected for the clinical study. Twenty patients were included in the study and the ketorolac/lidocaine wafer was assessed versus a market product. Visual pain analog was evaluated daily for the first week and wound healing index was evaluated for one week, two weeks and one month following the procedure. The developed ketorolac/lidocaine polymeric wafer proved to be an effective method of reducing pain and discomfort together with enhancing wound healing following gingivectomy.

The red flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), is an economically important pest of stored products. As possible alternative to conventional insecticides for its management, plant essential oils have gained interest owing to their effectiveness and eco-friendly features. However, they also show some drawbacks, such as low stability, poor water solubility and diffusion, and limited persistence in the environment. A good strategy to overcome these disadvantages is represented by green nanotechnologies. Herein, we developed a nanoemulsion based on the essential oil from Pimpinella anisum L. (Apiaceae) containing 81.2% of ( E )-anethole and evaluated its toxicity on T. castaneum adults and F 1 progeny, as well as its morphological and histological impact. The aniseed oil nanoemulsion was characterized by the formation of a semi-solid interphase between oil and water; mean drop size was 198.9 nm, PDI was 0.303, zeta potential was − 25.4 ± 4.47 mV, and conductivity was 0.029 mS/cm. The nanoemulsion showed toxicity on T. castaneum (LC 50  = 9.3% v / v ), with a significant impact on its progeny. Morphological and histological damages triggered by feeding and exposure to the aniseed nanoemulsion were analyzed by scanning electron microscopy (SEM) and light microscopy. Overall, our findings showed that the development of nanoemulsions allows to improve the stability of P. anisum essential oil enhancing its efficacy against stored grain pests and contributing to reduce the use of harmful synthetic insecticides.

Vitiligo is a significant dermatological challenge affecting 0.5 to 2% of the global population. Despite the various existing medical approaches, current vitiligo treatments are far from ideal. The present study aimed to prepare and evaluate a film-forming gel of 5 fluorouracil (5FU) using different ratios of hydroxypropyl methylcellulose (HPMC) and Zein for treating vitiligo. The prepared film-forming gels were fully characterized in terms of morphology, Fourier-transform infrared spectroscopy, drug content, pH, drying time, in-vitro drug release, and clinical investigation. A 3 2 -full factorial design was used to study the impact of varying concentrations of HPMC (X1) and Zein (X2) on the percentage of 5FU released (Y1) from the prepared film-forming gels. Scanning electron microscopy (SEM) revealed a cross-linked network structure between polymers. An increase in HPMC concentration (2–4%) correlated with higher 5FU release, whereas increased Zein concentration (1–2%) resulted in reduced 5FU release. Furthermore, patients treated with 5FU film-forming gel after dermabrasion with fractional CO2 (FCO2) laser exhibited a significant decrease in JAK3 gene expression and higher effectiveness than those treated with FCO2 laser alone. Our results suggest that the film-forming gel of 5FU is promising as an effective formulation for treating vitiligo. Graphical Abstract

PurposeThe selective delivery of chemotherapeutic agent to the affected area is mainly dependent on the mode of drug loading within the delivery system. This study aims to compare the physical method to the chemical method on the efficiency of loading DOX.HCl to GNPs and the specific release of the loaded drug at certain tissue.MethodBifunctional polyethylene glycol with two different functionalities, the alkanethiol and the carboxyl group terminals, was synthesized. Then, DOX·HCl was covalently linked via hydrazone bond, a pH sensitive bond, to the carboxyl functional group and the produced polymer was used to prepare drug functionalized nanoparticles. Another group of GNPs was coated with carboxyl containing polymer; loading the drug into this system by the means of electrostatic adsorption. Finally, the prepared system were characterized with respect to size, shape and drug release in acetate buffer pH 5 and PBS pH 7.4 Also, the effect of DOX.HCl loaded systems on cell viability was assessed using MCF-7 breast cancer cell line.ResultsThe prepared nanoparticles were spherical in shape, small in size and monodisperse. The release rate of the chemically bound drug in the acidic pH was higher than the electrostatically adsorbed one. Moreover, both systems show little release at pH 7.4. Finally, cytotoxicity profiles against human breast adenocarcinoma cell line (MCF-7) exhibited greater cytotoxicity of the chemically bound drug over the electrostatically adsorbed one.ConclusionChemical binding of DOX·HCl to the carboxyl group of PEG coating GNPs selectively delivers high amount of drug to tumour-affected tissue which leads to reducing the unwanted effects of the drug in the non-affected ones.

Vitiligo is a significant dermatological challenge affecting 0.5 to 2% of the global population. Despite the various existing medical approaches, current vitiligo treatments are far from ideal. The present study aimed to prepare and evaluate a film-forming gel of 5 fluorouracil (5FU) using different ratios of hydroxypropyl methylcellulose (HPMC) and Zein for treating vitiligo. The prepared film-forming gels were fully characterized in terms of morphology, Fourier-transform infrared spectroscopy, drug content, pH, drying time, in-vitro drug release, and clinical investigation. A 3 -full factorial design was used to study the impact of varying concentrations of HPMC (X1) and Zein (X2) on the percentage of 5FU released (Y1) from the prepared film-forming gels. Scanning electron microscopy (SEM) revealed a cross-linked network structure between polymers. An increase in HPMC concentration (2-4%) correlated with higher 5FU release, whereas increased Zein concentration (1-2%) resulted in reduced 5FU release. Furthermore, patients treated with 5FU film-forming gel after dermabrasion with fractional CO2 (FCO2) laser exhibited a significant decrease in JAK3 gene expression and higher effectiveness than those treated with FCO2 laser alone. Our results suggest that the film-forming gel of 5FU is promising as an effective formulation for treating vitiligo.

Recently, Digital Twin (DT) has a growth revolution by increasing Artificial Intelligence (AI) techniques and relative technologies as the Internet of Things (IoT). They may be considered as the panacea for DT technology for various applications in the real world such as manufacturing, healthcare, and smart cities. The integration of DT and AI is a new avenue for open research in the upcoming days. However, for exploring the issues of developing Digital Twins, there are interesting in identifying challenges with standardization ensures future developments in this innovative theme. This paper first presents the Digital Twins concept, challenges, and applications. Afterward, it discusses the incorporation of AI and DT for developing various IoT-based applications with exploring the challenges and opportunities in this innovative arena. Then, developing tools are presented for exploring the digital twins' system implementation. Further, a review of recent DT-based AI approaches is presented. Finally, a discussion of open research directions in this innovative theme is presented.

Salinity stress negatively affects the growth and yield of crops worldwide. Onion ( Allium cepa L.) is moderately sensitive to salinity. Beneficial microorganisms can potentially confer salinity tolerance. This study investigated the effects of endomycorrhizal fungi (M), Pseudomonas putida (Ps) and their combination (MPs) on onion growth under control (0 ppm), moderate (2000 ppm) and high (4000 ppm) NaCl salinity levels. A pot experiment was conducted with sandy loam soil and onion cultivar Giza 20. Results showed that salinity reduced growth attributes, leaf pigments, biomass and bulb yield while increasing oxidative stress markers. However, individual or combined inoculations significantly increased plant height, bulb diameter and biomass production compared to uninoculated plants under saline conditions. MPs treatment provided the highest stimulation, followed by Pseudomonas and mycorrhizae alone. Overall, dual microbial inoculation showed synergistic interaction, conferring maximum benefits for onion growth, bulbing through integrated physiological and biochemical processes under salinity. Bulb yield showed 3.5, 36 and 83% increase over control at 0, 2000 and 4000 ppm salinity, respectively. In conclusion, combined application of mycorrhizal-Pseudomonas inoculations (MPs) effectively mitigate salinity stress. This approach serves as a promising biotechnology for ensuring sustainable onion productivity under saline conditions.

Thin films of ZnO and ZnO/carbon nanotubes (CNTs) are prepared and used as CO2 gas sensors. The spray pyrolysis method was used to prepare both ZnO and ZnO/CNTs films, with CNTs first prepared using the chemical vapor deposition method (CVD). The chemical structure and optical analyses for all the prepared nanomaterials were performed using X-ray diffraction (XRD), Fourier transformer infrared spectroscopy (FTIR), and UV/Vis spectrophotometer devices, respectively. According to the XRD analysis, the crystal sizes of ZnO and ZnO/CNTs were approximately 50.4 and 65.2 nm, respectively. CNTs have average inner and outer diameters of about 3 and 13 nm respectively, according to the transmitted electron microscope (TEM), and a wall thickness of about 5 nm. The detection of CO2 is accomplished by passing varying rates of the gas from 30 to 150 sccm over the prepared thin-film electrodes. At 150 sccm, the sensitivities of ZnO and ZnO/CNTs sensors are 6.8% and 22.4%, respectively. The ZnO/CNTs sensor has a very stable sensitivity to CO2 gas for 21 days. Moreover, this sensor has a high selectivity to CO2 in comparison with other gases, in which the ZnO/CNTs sensor has a higher sensitivity to CO2 compared to H2 and C2H2.

Four novel substituted imidazole derivatives—5a (Kim-161), 5b (Kim-111), 5c (Kim-261), and 5d (Kim-231) were evaluated for their antiproliferative activity against urothelial carcinoma. Among these, the two derivatives Kim-161 (5a) and Kim-111 (5b) demonstrated potent cytotoxicity against the T24 transitional carcinoma cell line, with IC 50 values of 56.11 µM and 67.29 µM, respectively, as determined by MTT assay. Further mechanistic investigations revealed that these compounds modulate key pathways involved in cancer progression including cell cycle regulation; (p53), oncogenic signaling (Kras), cell apoptosis; (BAX and caspase 3), inflammatory response (Interleukin 6 (IL6), Tumor Necrosis Factor alpha (TNFα), and Nuclear Factor kappa B (NF-κB), autophagy regulation (phosphoinositide 3-kinase signaling (PIK3CA) and its targets protein kinase Akt and mammalian target of rapamycin (mTOR) and metastasis (Matrix metalloproteinase-9 (MMP-9)). Molecular docking and dynamic simulations against key cancer targets PTK6, FLT3, and BCL-2 revealed exceptional binding affinity and stable protein-ligand complexes. Furthermore, these compounds exhibited favorable drug-like properties, including optimal physicochemical and pharmacokinetic profiles. This integrated approach, combining the in vitro validation and computational modeling, places Kim-161 and Kim-111 as promising lead compounds for targeted urothelial carcinoma therapy. The findings underscore the therapeutic potential of dual kinase/tubulin inhibition in combating aggressive malignancies, offering a robust foundation for further preclinical development.