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.

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.

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.

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.

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.

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.

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.

In vitro study of the effect of resveratrol purified from the skin of Iraqi black grape (Vitis vinifera) on lymphocyte cultures isolated from the blood of patients with lymphoma.

The natural stilbene compound resveratrol (RSV) was extracted and purified locally from the black grape skin (Vitis vinifera) cultivated in Iraq. Cultures of human peripheral lymphocytes were obtained from the blood samples of patients with and without lymphoma to be treated with RSV at different concentrations. Three RSV concentration levels were subjected to isolated lymphocytes from blood samples of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and without lymphoma to estimate the change in TNF-α and IL-10. Resveratrol seemed to differently affect cytokines level in normal and lymphoma lymphocytes in relation to its concentration. The lowest resveratrol concentration (50 µg/ml) decreased TNF-α levels for patients without lymphoma and all NHL patients in contrast to the HL sample. Treating normal lymphocytes with a higher dose (1000 µg/ml) might elevate the levels of TNF-α in almost all samples. There was an inverse relationship between both cytokines in most treatments; with the increase in TNF-α level, there was a decrease in IL-10 level except in HL and normal lymphocytes treatment. The locally purified resveratrol could serve as a multi-target drug that modulates the immune system to improve body defense in patients suffering from lymphoma and in patients without lymphoma by altering cytokine levels in response to different resveratrol concentrations in a different manner.

Microbial Inactivation: Gaseous or Aqueous Ozonation?

For decades, ozone has been known to have antimicrobial properties when dissolved or generated in water and when utilized in its gaseous form on different substrates. This property (the ability to be used in air and water) makes it versatile and applicable to different industries. Although the medium of ozonation depends on the specific process requirements, some industries have the inherent flexibility of medium selection. Thus, it is important to evaluate the antimicrobial efficacy in both media at similar concentrations, an endeavor hardly reported in the literature. This study provides insights into ozone's efficacy in air and water using two Gram-negative bacteria (Escherichia coli NTCC1290 and Pseudomonas aeruginosa NCTC10332), two Gram-positive bacteria (Staphylococcus aureus ATCC25923 and Streptococcus mutans), and two fungi (Candida albicans and Aspergillus fumigatus). For gaseous ozonation, we utilized a custom-made ozone chamber (equipped with ultraviolet lamps), whereas an electrolysis oxygen radical generator was applied for ozone generation in water. During gaseous ozonation, the contaminated substrates (fabric swatches inoculated with bacterial and fungal suspensions) were suspended in the chamber, whereas the swatches were immersed in ozonated water for aqueous ozone treatment. The stability of ozone nanobubbles and their resulting impact on the aqueous disinfection efficiency were studied via dynamic light scattering measurements. It was observed that ozone is more effective in air than in water on all tested organisms except Staphylococcus aureus. The presented findings allow for the adjustment of the treatment conditions (exposure time and concentration) for optimal decontamination, particularly when a certain medium is preferred for ozonation.

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.

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.

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.

Gestational breast cancer in a patient with Crohn's disease: two case reports.

BACKGROUND: Diagnosis of breast cancer during gestation is a rare occurrence. In addition, the diagnosis of breast cancer in a patient with Crohn's disease is not common. We present a rare case of gestational breast cancer in a patient with Crohn's disease, with a concurrent breast cancer diagnosis in her sister. CASE PRESENTATION: A 31-year-old Syrian woman with Crohn's disease was diagnosed with breast cancer at 30 weeks gestation; she received neoadjuvant chemotherapy during gestation. Incidentally, her 37-year-old sister was also diagnosed concomitantly with breast cancer. Both sisters underwent and successfully completed surgery and adjuvant therapy. At a 5-year review, both patients showed no signs of recurrence. The Crohn's disease symptoms have also improved after chemotherapy, and the baby born after gestational chemotherapy is currently 5 years old with normal psychomotor development and without any congenital malformations. CONCLUSIONS: This case report highlights the impact of gestation on breast cancer outcomes, the possibility of giving chemotherapy during gestation, and the effect of chemotherapy on the symptoms of Crohn's disease.

First case of chronic cell leukemia discovered incidentally in extra-saccular inguinal lymph node during laparoscopic bilateral inguinal hernia repair. Case report and literature review.

INTRODUCTION: Chronic cell leukemia discovered incidentally in extra-saccular inguinal lymph node during laparoscopic bilateral inguinal hernia repair is extremely rare. PRESENTATION OF CASE: 62-year-old Romanian male presented at the outpatient general surgery clinic in April 2019 complaining of bilateral inguinal swelling that gradually increased in size mainly on right side and was diagnosed with bilateral inguinal hernia. During the laparoscopic repair of the hernia, a large lymph node in the left femoral canal was incidentally observed. Histopathologic, immunohistochemical, and flowcytometric evaluation of the excised specimen confirmed chronic lymphocytic leukemia/small lymphocytic lymphoma. DISCUSSION: Whole body CT showed supra and infra-diaphragmatic lymphadenopathy, and few small subsolid pulmonary nodules, possibly metastatic. Splenomegaly and pancreatomegaly were also noted, suggesting lymphomatoid infiltration. CONCLUSION: There is need for cautious inspection and meticulous palpation of the inguinal area for any lymphadenopathy during routine inguinal hernia repair.

Bioguided Isolation of Cyclopenin Analogues as Potential SARS-CoV-2 Mpro Inhibitors from Penicillium citrinum TDPEF34.

SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease Mpro in vitro. The extract of Penicillium citrinum, TDPEF34, showed potential inhibition and was further analysed to identify potential Mpro inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 Mpro were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds 1 (isolated as two conformers of S- and R-isomers), 2, and 4 were found to have promising in vitro inhibitory activity towards Mpro, with an IC50 values range of 0.36-0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent Mpro inhibitors.

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.

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.