Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues.

Cellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. While endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single-cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence. Progerin-expressing ECs supported prolonged neutrophil adhesion and crawling in a cell autonomous manner that additionally mediated neutrophil-dependent microvascular leakage. Transcriptomic and immunofluorescence analysis of inflamed tissues identified elevated levels of EC CXCL1 on progerin-expressing ECs and functional blockade of CXCL1 suppressed the dysregulated neutrophil responses elicited by senescent ECs. Similarly, cultured progerin-expressing human ECs exhibited a senescent phenotype, were pro-inflammatory and prompted increased neutrophil attachment and activation. Collectively, our findings support the concept that senescent ECs drive excessive inflammation and provide new insights into the mode, dynamics, and mechanisms of this response at single-cell level.

Dry biofilms on polystyrene surfaces: the role of oxidative treatments for their mitigation.

Candida auris and Staphylococcus aureus are associated with a wide range of infections, as they exhibit multidrug resistance - a growing health concern. In this study, gaseous ozone, and ultraviolet-C (UVC) radiation are applied as infection control measures to inactivate dry biofilms of these organisms on polystyrene surfaces. The dosages utilised herein are 1000 and 3000 ppm.min for ozone and 2864 and 11592 mJ.cm-2 for UVC. Both organisms showed an increased sensitivity to UVC relative to ozone exposure in a bespoke decontamination chamber. While complete inactivation of both organisms (>7.5 CFU log) was realized after 60 mins of UVC application, this could not be achieved with ozonation for the same duration. However, a combined application of ozone and UVC yielded complete inactivation in only 20 mins. For both treatment methods, it was observed that dry biofilms of S. aureus were more difficult to inactivate than dry biofilms of C. auris. Compared to dry biofilms of C. auris, micrographs of wet C. auris biofilms revealed the presence of an abundance of extracellular material after treatments. Interestingly, wet biofilms were more difficult to inactivate than dry biofilms. These insights are crucial to preventing recalcitrant and recurrent infections via contact with contaminated polymeric surfaces.

Oxidative treatment can inactivate dry biofilms formed by C. auris and S. aureus.Both organisms showed an increased sensitivity to UVC compared to ozone.Dry biofilms of S. aureus were more difficult to inactivate than dry biofilms of C. auris.Wet biofilms of C. auris display a spongy appearance compared to its dry biofilms.Wet biofilms of C. auris proved more difficult to inactivate than its dry biofilms.

Ozone application in different industries: A review of recent developments.

Ozone - a powerful antimicrobial agent, has been extensively applied for decontamination purposes in several industries (including food, water treatment, pharmaceuticals, textiles, healthcare, and the medical sectors). The advent of the COVID-19 pandemic has led to recent developments in the deployment of different ozone-based technologies for the decontamination of surfaces, materials and indoor environments. The pandemic has also highlighted the therapeutic potential of ozone for the treatment of COVID-19 patients, with astonishing results observed. The key objective of this review is to summarize recent advances in the utilisation of ozone for decontamination applications in the above-listed industries while emphasising the impact of key parameters affecting microbial reduction efficiency and ozone stability for prolonged action. We realise that aqueous ozonation has received higher research attention, compared to the gaseous application of ozone. This can be attributed to the fact that water treatment represents one of its earliest applications. Furthermore, the application of gaseous ozone for personal protective equipment (PPE) and medical device disinfection has not received a significant number of contributions compared to other applications. This presents a challenge for which the correct application of ozonation can mitigate. In this review, a critical discussion of these challenges is presented, as well as key knowledge gaps and open research problems/opportunities.

Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors.

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 Mpro with IC50 value of 0.47 µM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 Mpro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related Mpro inhibitors.

Photophysical and Electrochemical Properties of Highly π-Conjugated Bipolar Carbazole-1,3,4-Oxadiazole-based D-π-A Type of Efficient Deep Blue Fluorescent Dye.

In this contribution, we have designed and synthesized a novel carbazole-1,3,4-oxadiazole based bipolar fluorophore (E)-2-(4-(4-(9H-carbazol-9-yl)styryl)phenyl)-5-(4-(tertbutyl) phenyl)-1,3,4-oxadiazole (CBZ-OXA-IV). Wittig reaction is utilised for the synthesis of the designed bipolar target compound CBZ-OXA-IV. 1H NMR, 13C NMR, FT-IR and ESI-MS results confirmed the designed chemical structure of the fluorophore CBZ-OXA-IV. The photophysical properties have been investigated in detail using UV-Vis absorption, photoluminescence spectroscopy. Also, the photoluminescence studies on solid state samples (as thin films) were carried out. The CBZ-OXA-IV dye emits intense deep blue fluorescence with observed absorption and emission maxima occurring are at 353 nm and 470 nm, respectively. Fluorophore CBZ-OXA-IV has shown high Stokes shift of 7052 cm-1. The experimentally measured optical band gap ([Formula: see text]) value is found to be 3.01 eV and the fluorescence quantum yields (Φf) is 0.40. The intramolecular charge transfer property of CBZ-OXA-IV dye was examined by using photophysical properties such as absorption, emission in different solvents of different varying polarities. In addition, Density Functional Theory computations are studied in detail including the MEP surface plots and natural bond orbital analysis. The electrochemical properties have been investigated in detail by using cyclic voltammetry measurements. Thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) measurement results display a high thermal stability with decomposition temperature (Td5%) 387 °C and a large glass transition temperature (Tg) of 98 °C. The obtained results demonstrated that the novel bipolar fluorophore CBZ-OXA-IV could play an important role in organic optoelectronics and possibly can be utilized as bipolar transport materials for electroluminescence applications in optoelectronic devices/OLEDs.

Potent antiplasmodial alkaloids from the rhizobacterium Pantoea agglomerans as hemozoin modulators.

Global health concern regarding malaria has increased since the first report of artemisinin-resistant Plasmodium falciparum (Pf) two decades ago. The current therapies suffer various drawbacks such as low efficacy and significant side effects, alarming for an urgent need of more effective and less toxic drugs with higher patient compliance. Chemical entities with natural origins become progressively attractive as new drug leads due to their structural diversity and bio-compatibility. This study initially aimed at the targeted isolation of hydroxyquinoline derivatives following our published genomics and metabolomics study of Pantoea agglomerans (Pa). Fermentation of Pa on a pre-selected medium followed by chromatographic isolation, NMR and HRMS analyses led to the characterisation of one new hydroxyquinoline alkaloid together with another six known congeners and two known hydroxyquinolone derivatives. When screened for their antimalarial activity by high throughput screening against asexual blood-stage parasites, almost all compounds showed potent and selective sub-micromolar activities. Computational investigation was performed to identify the antiplasmodial potential targets. Ligand-based similarity search predicted the tested compounds to act as hemozoin inhibitors. Computational target identification results were further validated by competitive hemozoin inhibitory properties of hydroxyquinoline and hydroxyquinolone derivatives in vitro. The overall results suggest this natural scaffold is of potential to be developed as antimalarial drug lead.

Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2's spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein's RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.

The association between self-reported workload and perceptions of patient safety culture: A study of intensive care unit nurses.

AIM AND OBJECTIVE: This study aimed to examine the association between workload and patient safety culture (PSC) among intensive care unit (ICU) nurses. BACKGROUND: ICU nurses play a vital role in promoting patient safety and are essential indicators in any healthcare system including ICUs. Research studies focusing on the relationship between nursing workload and PSC among ICU nurses are limited. DESIGN: Descriptive correlational design. METHODS: The study participants involved 380 ICU nurses at two hospitals in Riyadh, Saudi Arabia. Data were collected between February 2019-April 2019 and were analysed using SPSS v.22 statistical software. This study was guided by the STROBE checklist. RESULTS: The results showed that ICU nurses have high positive perceptions in the following PSC subscales: teamwork within units, organisational learning-continuous improvement, frequency of events reported, feedback and communication about error, management support for patient safety, teamwork across units, supervisor/manager expectations and actions promoting patient safety, handoffs and transitions, nonpunitive response to errors, staffing and overall perceptions of patient safety. However, the participants collectively considered the overall grade on patient safety as poor. The participants had high mean scores in physical demand, effort, mental demand and overall workload. A statistically significant variability existed in the mean scores of the PSC subscales and workload of ICU nurses. The overall workload was significantly and negatively associated with the PSC perceptions of ICU nurses. CONCLUSION: The ICU nurses experienced high overall workload, physical demand, effort and mental demand which influenced the poor grade of their overall perceived PSC. RELEVANCE TO CLINICAL PRACTICE: Identifying differences and associations with the perceptions of ICU nurses regarding workload and PSC is important because such perceptions may affect their delivery of nursing care. Hospital and nursing administrators must use the study results to find strategies that address workload issues and enhance patient safety.

Structural Features of Micelles of Zwitterionic Dodecyl-phosphocholine (C12PC) Surfactants Studied by Small-Angle Neutron Scattering.

Small-angle neutron scattering (SANS) was used to investigate the size and shape of zwitterionic dodecyl phosphocholine (C12PC) micelles formed at various concentrations above its critical micelle concentration (CMC = 0.91 mM). The predominant spherical shape of micelles is revealed by SANS while the average micellar size was found to be broadly consistent with the hydrodynamic diameters determined by dynamic light scattering (DLS). Cryogenic tunneling electron microscopy (cryo-TEM) shows a uniform distribution of structures, proposing micelle monodispersity ( Supporting Information ). H/D substitution was utilized to selectively label the chain, head, or entire surfactant so that structural distributions within the micellar assembly could be investigated using fully protonated, head-deuterated, and tail-deuterated PC surfactants in D2O and fully deuterated surfactants in H2O. Using the analysis software we have developed, the four C12PC contrasts at a given concentration were simultaneously analyzed using various core-shell models consisting of a hydrophobic core and a shell representing hydrated polar headgroups. Results show that at 10 mM, C12PC micelles can be well represented by a spherical core-shell model with a core radius and shell thicknesses of 16.9 ± 0.5 and 10.2 ± 2.0 Å (total radius 27.1 ± 2.0 Å), respectively, with a surfactant aggregation number of 57 ± 5. As the concentration was increased, the SANS data revealed an increase in core-shell mixing, characterized by the emergence of an intermediate mixing region at the spherical core-shell interface. C12PC micelles at 100 mM were found to have a core radius and shell thicknesses of 19.6 ± 0.5 and 7.8 ± 2.0 Å, with an intermediate mixing region of 3.0 ± 0.5 Å. Further reduction in the shell thickness with concentration was also observed, coupled with an increased mixing of the core and shell regions and a reduction in miceller hydration, suggesting that concentration has a significant influence on surfactant packing and aggregation within micelles.

Phylogenetic analysis of Staphylococcus aureus enterotoxin A gene in Iraqi breed cows with bovine mastitis: Implications for disease management.

Background: Although milk is nutritionally valuable, it also serves as a significant medium for the transmission of pathogens and their toxins. Aim: This study aimed to investigate the role of enterotoxin gene A (SEA) in the development of bovine mastitis. We accomplished this by examining milk through polymerase chain reaction (PCR) testing, amino acid substitution analysis, and phylogenetic analysis. Methods: A total of fifty milk samples were collected from locally bred dairy cows in Al-Diwaniyah, located in southern Iraq. We employed the VITEK-2 platform to validate the diagnosis of Staphylococcus aureus and confirm the results of routine tests (culturing and biochemical tests). Subsequently, the genetic mutation and phylogeny analysis were achieved utilizing DNA sequencing to 16S rRNA and enterotoxin A genes. Results: 66% (33/50) of the milk samples found to be contain S. aureus by the VITEK-2 system. Furthermore, 25/33 of the samples were positive by the PCR test. While 60% (15 out of 25) tested positive for the SEA gene. After genomic analysis, we identified amino acid substitutions of serine, glutamine with arginine, tyrosine with cysteine, and aspartic acid with glycine at positions 9, 101, 119, 187, and 191. The phylogenetic investigation demonstrated a genetic relationship between our isolates (Iraqi isolates) and isolates from Indian and the United States. Conclusion: Our study indicated the widespread distribution of the enterotoxin gene A (SEA) of S. aureus among dairy cows. The molecular study revealed significant changes in key amino acids that could play an important role in the bacterium's pathogenesis. The phylogenetic similarities among S. aureus samples from various countries suggest that the bacteria has spread globally.

Interfacial assembly of lipopeptide surfactants on octyltrimethoxysilane-modified silica surface.

The adsorption of a series of cationic lipopeptide surfactants, C14Kn (where C14 denotes the myristic acyl chain and Kn represents n number of lysine residues) at the hydrophobic solid/water interface has been studied using spectroscopic ellipsometry (SE) and neutron reflection (NR). The hydrophobic C8 surface was prepared by grafting a monolayer of octyltrimethoxysilane on the silicon surface. SE was used to follow the dynamic adsorption from these lipopeptide surfactants and the amount was found to undergo a fast increase within the first 2-3 min, followed by a much slower process tending to equilibration in the subsequent 15-20 min. Lipopetide surfactants with n = 1-4 showed similar dynamic features, indicating that the interaction between the acyl chain and the C8 surface is the main driving force for adsorption. The saturation adsorption amount of C14Kn at the C8/water interface was found to be inversely related to the increasing number of Lys residues in the head group due to the increase of steric hindrance and electrostatic repulsion between the head groups. Solution concentration had a significant effect on the initial adsorption rate, similar to the feature observed from nonionic surfactants CmEn. The structure of the adsorbed layers was studied by NR in conjunction with isotopic contrasts. The layer formed by the head groups of C14K1 was 10 Å thick, and those formed by C14K2, C14K3 and C14K4 head groups were all about 13 Å thick. In contrast, the thicknesses of the layers formed by hydrophobic tails of C14K1, C14K2 C14K3, and C14K4 were found to be 17, 13, 10, and 10 Å, respectively, resulting in the steady increase of area per molecule at the interface from 29 ± 2 Å(2) for C14K1 to 65 ± 2 Å(2) for C14K4. Thus, with an increase in the head group length, the molecules in the adsorbed layer tended to lie down upon adsorption.

Fluoridated orthodontic adhesives: Implications of release and recharge and their impact on shear bond strength in demineralized tooth surfaces.

Background: This study measured fluoride release from a light-cured orthodontic adhesive resin (Vega type) at three time intervals (one day, one week, and one month), investigated the rechargeability of the resin, and assessed its impact on shear bond strength in demineralized tooth surfaces. Methods: This study used 30 recently extracted upper premolar teeth to explore the effects of fluoride release over specific time intervals. The teeth underwent demineralization and were categorized into groups based on time intervals: one day, one week, and one month. Subgroups within each interval underwent fluoride recharging through fluoride varnish application. Fluoride release and shear bond strength were assessed after etching with phosphoric acid gel, applying the orthodontic adhesive, and curing. The samples were stored in deionized water. Fluoride quantification used a selective electrode, while shear bond strength assessment employed a universal testing machine. Finally, statistical analysis of the data was performed using SPSS 22. Results: The study found that after one month, the adhesive had the highest fluoride release and shear bond strength mean values. There were significant differences in fluoride release and shear bond strength between the various groups studied. Conclusion: The application of fluoride varnish around the orthodontic bracket resulted in a positive effect on the shear bond strength of the bracket.

Ozone Decontamination of Medical and Nonmedical Devices: An Assessment of Design and Implementation Considerations.

The control of infectious diseases can be improved via carefully designed decontamination equipment and systems. Research interest in ozone (a powerful antimicrobial agent) has significantly increased over the past decade. The COVID-19 pandemic has also instigated the development of new ozone-based technologies for the decontamination of personal protective equipment, surfaces, materials, and indoor environments. As this interest continues to grow, it is necessary to consider key factors affecting the applicability of lab-based findings to large-scale systems utilizing ozone. In this review, we present recent developments on the critical factors affecting the successful deployments of industrial ozone technologies. Some of these include the medium of application (air or water), material compatibility, efficient circulation and extraction, measurement and control, automation, scalability, and process economics. We also provide a comparative assessment of ozone relative to other decontamination methods/sterilization technologies and further substantiate the necessity for increased developments in gaseous and aqueous ozonation. Modeling methodologies, which can be applied for the design and implementation of ozone contacting systems, are also presented in this review. Key knowledge gaps and open research problems/opportunities are extensively covered including our recommendations for the development of novel solutions with industrial importance.

The synergistic antibacterial activity of ozone and surfactant mists.

The microbiological safety of medical equipment and general surfaces is paramount to both the well-being of patients and the public. The application of ozone (a potent oxidant) has been recognised and implemented for this purpose, globally. However, it has primarily been utilised in the gaseous and aqueous forms. In this study, we investigate the potency of fine ozone mists and evaluate the synergistic effect when combined with cationic, anionic and non-ionic surfactants (dodecyl trimethyl ammonium bromide - DTAB, sodium dodecyl sulfate - SDS, alkyl polyglycoside - APG) as well as polyethylene glycol (PEG). Ozone mist is generated via a nebuliser (equipped with a compressed gas stream) and the piezoelectric method; whereas fabric substrates contaminated with Escherichia coli and Staphylococcus aureus are utilised in this study. Contamination levels on the fabric swatches are evaluated using agar dipslides. Compared to gaseous ozonation and aqueous ozonation (via nanobubble generation), the produced ozone mists showed significantly inferior antimicrobial properties for the tested conditions (6 ppm, 5-15 min). However, the hybrid mist-based application of 'ozone + surfactants' and 'ozone + PEG' showed considerable improvements compared to their independent applications (ozone mist only and surfactant mist only). The 'ozone + DTAB' mist had the highest activity, with better results observed with the micron-mist nebuliser than the piezoelectric transducer. We propose a likely mechanism for this synergistic performance (micellar encapsulation) and demonstrate the necessity for continued developments of novel decontamination technologies.

Gelatin nanofibers: Recent insights in synthesis, bio-medical applications and limitations.

The use of gelatin and gelatin-blend polymers as environmentally safe polymers to synthesis electrospun nanofibers, has caused a revolution in the biomedical field. The development of efficient nanofibers has played a significant role in drug delivery, and for use in advanced scaffolds in regenerative medicine. Gelatin is an exceptional biopolymer, which is highly versatile, despite variations in the processing technology. The electrospinning process is an efficient technique for the manufacture of gelatin electrospun nanofibers (GNFs), as it is simple, efficient, and cost-effective. GNFs have higher porosity with large surface area and biocompatibility, despite that there are some drawbacks. These drawbacks include rapid degradation, poor mechanical strength, and complete dissolution, which limits the use of gelatin electrospun nanofibers in this form for biomedicine. Thus, these fibers need to be cross-linked, in order to control its solubility. This modification caused an improvement in the biological properties of GNFs, which made them suitable candidates for various biomedical applications, such as wound healing, drug delivery, bone regeneration, tubular scaffolding, skin, nerve, kidney, and cardiac tissue engineering. In this review an outline of electrospinning is shown with critical summary of literature evaluated with respect to the various applications of nanofibers-derived gelatin.

Controllable stabilization of poly(N-isopropylacrylamide)-based microgel films through biomimetic mineralization of calcium carbonate.

Two types of thermoresponsive microgels, poly(N-isopropylacrylamide) (PNIPAM) microgels and poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAMAC) microgels were synthesized and used as templates for the mineralization of amorphous calcium carbonate (ACC) by diffusion of CO(2) vapor under ambient conditions. Thermosensitive PNIPAM/CaCO(3) hybrid macroscopic hydrogels and micrometer-sized PNIPAMAC/CaCO(3) hybrid microgels were controllably obtained and different mineralization mechanistic processes were proposed. The impact of the loaded CaCO(3) on the size, morphology, stability, and thermosensitivity of the microgels was also analyzed. PNIPAM/CaCO(3) hybrid macrogels had a slight decrease in thermoresponsive phase transition temperature, while PNIPAMAC/CaCO(3) hybrid microgels showed a clear increase in phase transition temperature. The difference reflected different amount and location of ACC in the gel network, causing different interactions with polymer chains. The PNIPAMAC/CaCO(3) microgels formed stable monolayer films on bare silica wafers and glass coverslips upon drying. The microgel films could facilitate the attachment and growth of 3T3 fibroblast cells and their subsequent detachment upon temperature drop from 37 °C to the ambient condition around 20 °C, thus, offering a convenient procedure for cell harvesting.

High-value biochemical products & applications of freshwater eukaryotic microalgae.

A shift in public perception of the health and nutritional benefits of organic supplements and skin care products has led to a surge in high-value products being extracted from microalgae. Traditional forms of microalgae products were proteins, lipids and carbohydrates. However, in recent times the extraction of carotenoids (pigments), polyunsaturated acids (PUFAs), vitamins, phytosterols and polyphenols has increased significantly. Despite the diversity of products most research has failed to scale up production to industrial scale due to economic constraints and productivity capacities. It is clear that the main market drivers are the pharmaceutical and nutraceutical industries. This paper reviews the high-value products produced from freshwater eukaryotic microalgae. In addition, the paper also considers the biochemical properties of eukaryotic microalgae to provide a comparative analysis of different strains based on their high-value product content.

Design, Synthesis and Antitumor Activity of Novel Dispiro[oxindole-cyclohexanone]- pyrrolidines.

BACKGROUND: Spirooxindoles are privileged scaffolds in medicinal chemistry, which were identified through Wang's pioneering work as inhibitors of MDM2-p53 interactions. OBJECTIVE: To design and synthesize 2,6-diarylidenecyclohexanones and dispiro[oxindole-cyclohexanone]- pyrrolidines having potential antitumor effect. METHODS: Dispiro[oxindole-cyclohexanone]-pyrrolidines 6a-h were synthesized in a regioselective manner via 1,3-dipolar cycloaddition reaction of 2,6-diarylidenecyclohexanones 3a-h, isatin, and sarcocine. Compounds 6a-h were alkylated to give (7-10)a,b. All compounds were evaluated in vitro for their antitumor activity and cytotoxic selectivity against breast cancer cell lines (MCF-7 and MDA-MB-231), breast fibrosis cell line (MCF10a), and placental cancer cell line (JEG-3). Molecular modeling inside the MDM2 binding site was performed using AutoDock4.2. RESULTS: Synthesized compounds showed antitumor activity comparable to tamoxifen and compounds 3a,b,f,g and 9a,b showed selective cytotoxicity against tumor cells but reduced toxicity toward MCF-10a cells. Molecular modelling shows that both classes of synthesized compounds are predicted to fit the deep hydrophobic cleft on the surface of MDM2 and mimic the interactions between p53 and MDM2. CONCLUSION: The synthesized compounds have antitumor activity against MCF-7, MDA-MB-231, and JEG-3. Few compounds showed a selective cytotoxic effect and may have the potential to inhibit MDM2 and stimulate p53. In the future, studies regarding the optimization of medicinal chemistry as well as mechanistic studies will be conducted to enhance the inhibition effect of identified compounds and elucidate their mechanism of action.

Application of Ultraviolet-C Radiation and Gaseous Ozone for Microbial Inactivation on Different Materials.

With the advent of the COVID-19 pandemic, there has been a global incentive for applying environmentally sustainable and rapid sterilization methods, such as ultraviolet-C radiation (UVC) and ozonation. Material sterilization is a requirement for a variety of industries, including food, water treatment, clothing, healthcare, medical equipment, and pharmaceuticals. It becomes inevitable when devices and items like protective equipment are to be reused on/by different persons. This study presents novel findings on the performance of these sterilization methods using four microorganisms (Escherichia coli , Staphylococcus aureus , Candida albicans , and Aspergillus fumigatus) and six material substrates (stainless steel, polymethyl methacrylate, copper, surgical facemask, denim, and a cotton-polyester fabric). The combination of both ozone and UVC generally yields improved performance compared to their respective applications for the range of materials and microorganisms considered. Furthermore, the effectiveness of both UVC and ozone was higher when the fungi utilized were smeared onto the nonabsorbent materials than when 10 µL droplets were placed on the material surfaces. This dependence on the contaminating liquid surface area was not exhibited by the bacteria. This study highlights the necessity of adequate UVC and ozone dosage control as well as their synergistic and multifunctional attributes when sterilizing different materials contaminated with a wide range of microorganisms.

Bacterial and fungal disinfection via ozonation in air.

Ozone treatment is an eco-friendly and cost-effective approach to achieve material disinfection, and this disinfection method is of utmost importance in the present global pandemic. The efficacy of ozone's oxidative potential on common microorganisms has been extensively studied, particularly in the food and water treatment industries. However, little is still understood regarding its antimicrobial capabilities for the treatment of textile substrates in air. In this study, fabric swatches inoculated with bacterial and fungal suspensions are exposed to ozone for different durations and at different ozone concentrations. Pathogenic bacteria (Escherichia coli, Staphylococcus aureus), and fungi (Aspergillus fumigatus, and Candida albicans), are the microbes utilised in this study. The efficacy of ozone is demonstrated by the complete removal of microbiota on the tested swatches when a concentration and exposure duration of 20 ppm and 4 mins are respectively maintained in a test ozone chamber. We expect the insights from this work to guide the development of new ozonation techniques capable of rapid sterilisation in industrial & public settings.