Iron/Copper/Phosphate nanocomposite as antimicrobial, antisnail, and wheat growth-promoting agent.

BACKGROUND: One of the current challenges is to secure wheat crop production to meet the increasing global food demand and to face the increase in its purchasing power. Therefore, the current study aimed to exploit a new synthesized nanocomposite to enhance wheat growth under both normal and drought regime. The effectiveness of this nanocomposite in improving the microbiological quality of irrigation water and inhibiting the snail's growth was also assessed. RESULTS: Upon the employed one-step synthesis process, a spherical Fe/Cu/P nanocomposite was obtained with a mean particle size of 4.35 ± 1.524 nm. Cu2+, Fe2+, and P4+ were detected in the dried nanocomposite at 14.533 ± 0.176, 5.200 ± 0.208, and 34.167 ± 0.203 mg/ml concentration, respectively. This nanocomposite was found to exert antibacterial activity against Escherichia coli and Salmonella typhi. It caused good inhibition percent against Fusarium oxysporum (43.5 ± 1.47%) and reduced both its germination rate and germination efficiency. The lethal concentration 50 (LC50) of this nanocomposite against Lanistes carinatus snails was 76 ppm. The treated snails showed disturbance in their feeding habit and reached the prevention state. Significant histological changes were observed in snail digestive tract and male and female gonads. Drought stress on wheat's growth was mitigated in response to 100 and 300 ppm treatments. An increase in all assessed growth parameters was reported, mainly in the case of 100 ppm treatment under both standard and drought regimes. Compared to control plants, this stimulative effect was accompanied by a 2.12-fold rise in mitotic index and a 3.2-fold increase in total chromosomal abnormalities. CONCLUSION: The finding of the current study could be employed to mitigate the effect of drought stress on wheat growth and to enhance the microbiological quality of irrigation water. This is due to the increased efficacy of the newly synthesized Fe/Cu/P nanocomposite against bacteria, fungi, and snails. This methodology exhibits potential for promoting sustainable wheat growth and water resource conservation.

Global production patterns: Understanding the relationship between greenhouse gas emissions, agriculture greening and climate variability.

Climate change due to increased greenhouse gas emissions (GHG) in the atmosphere has been consistently observed since the mid-20th century. The profound influence of global climate change on greenhouse gas (GHG) emissions, encompassing carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O), has established a vital feedback loop that contributes to further climate change. This intricate relationship necessitates a comprehensive understanding of the underlying feedback mechanisms. By examining the interactions between global climate change, soil, and GHG emissions, we can elucidate the complexities of CO2, CH4, and N2O dynamics and their implications. In this study, we evaluate the global climate change relationship with GHG globally in 246 countries. We find a robust positive association between climate and GHG emissions. By 2100, GHG emissions will increase in all G7 countries and China while decreasing in the United Kingdom based on current economic growth policies, resulting in a net global increase, suggesting that climate-driven increase in GHG and climate variations impact crop production loss due to soil impacts and not provide climate adaptation. The study highlights the diverse strategies employed by G7 countries in reducing GHG emissions, with France leveraging nuclear power, Germany focusing on renewables, and Italy targeting its industrial and transportation sectors. The UK and Japan are making significant progress in emission reduction through renewable energy, while the US and Canada face challenges due to their industrial activities and reliance on fossil fuels.

Long-term effectiveness and persistence of ustekinumab and TNF inhibitors in patients with psoriatic arthritis: final 3-year results from the PsABio real-world study.

OBJECTIVES: To evaluate real-world persistence and effectiveness of the IL-12/23 inhibitor, ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis over 3 years. METHODS: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or a TNFi. Persistence and effectiveness (achievement of clinical Disease Activity for PSA (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very LDA (MDA/VLDA)) were assessed every 6 months. Safety data were collected over 3 years. Analyses to compare the modes of action were adjusted on baseline differences by propensity scores (PS). RESULTS: In 895 patients (mean age 49.8 years, 44.7% males), at 3 years, the proportion of patients still on their initial treatments was similar with ustekinumab (49.9%) and TNFi (47.8%). No difference was seen in the risk of stopping/switching; PS-adjusted hazard ratio (95% CI) for stopping/switching ustekinumab versus TNFi was 0.87 (0.68 to 1.11). In the overall population, cDAPSA LDA/remission was achieved in 58.6%/31.4% ustekinumab-treated and 69.8%/45.0% TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63 to 1.26) for cDAPSA LDA; 0.72 (0.50 to 1.05) for remission. MDA/VLDA was achieved in 41.4%/19.2% of ustekinumab-treated and 54.2%/26.9% of TNFi-treated patients with overlapping PS-adjusted ORs. A greater percentage of TNFi-treated patients achieved effectiveness outcomes. Both treatments exhibited good long-term safety profiles, although ustekinumab-treated patients had a lower rate of adverse events (AEs) versus TNFi. CONCLUSION: At 3 years, there was generally comparable persistence after ustekinumab or TNFi treatment, but AE rates were lower with ustekinumab.

Gender-specific differences in patients with psoriatic arthritis receiving ustekinumab or tumour necrosis factor inhibitor: real-world data.

OBJECTIVE: Investigate effects of gender on disease characteristics and treatment impact in patients with PsA. METHODS: PsABio is a non-interventional European study in patients with PsA starting a biological DMARD [bDMARD; ustekinumab or TNF inhibitor (TNFi)]. This post-hoc analysis compared persistence, disease activity, patient-reported outcomes and safety between male and female patients at baseline and 6 and 12 months of treatment. RESULTS: At baseline, disease duration was 6.7 and 6.9 years for 512 females and 417 males respectively. Mean (95% CI) scores for females vs males were: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), 32.3 (30.3, 34.2) vs 26.8 (24.8, 28.9); HAQ-Disability Index (HAQ-DI), 1.3 (1.2, 1.4) vs 0.93 (0.86, 0.99); total PsA Impact of Disease-12 (PsAID-12) score, 6.0 (5.8, 6.2) vs 5.1 (4.9, 5.3), respectively. Improvements in scores were smaller in female than male patients. At 12 months, 175/303 (57.8%) female and 212/264 (80.3%) male patients achieved cDAPSA low disease activity, 96/285 (33.7%) and 137/247 (55.5%), achieved minimal disease activity (MDA), respectively. HAQ-DI scores were 0.85 (0.77, 0.92) vs 0.50 (0.43, 0.56), PsAID-12 scores 3.5 (3.3, 3.8) vs 2.4 (2.2, 2.6), respectively. Treatment persistence was lower in females than males (P ≤ 0.001). Lack of effectiveness was the predominant reason to stop, irrespective of gender and bDMARD. CONCLUSIONS: Before starting bDMARDs, females had more severe disease than males and a lower percentage reached favourable disease states, with lower persistence of treatment after 12 months. A better understanding of the mechanisms underlying these differences may improve therapeutic management in females with PsA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02627768.

Insight into the Hantaan virus RNA-dependent RNA polymerase inhibition using in-silico approaches.

The Hantaan virus (HTN) is a member of the hantaviridae family. It is a segmented type, negative-strand virus (sNSVs). It causes hemorrhagic fever with renal syndrome, which includes fever, vascular hemorrhage, and renal failure. This illness is one of the most serious hemorrhagic diseases in the world, and it is a major public health concern due to its high mortality rate. The Hantaan virus RNA-dependent RNA polymerase complex (RdRp) is involved in viral RNA transcription and replication for the survival and transmission of this virus. Therefore, it is a primary target for antiviral drug development. Interference with the endonucleolytic "cap-snatching" reaction by the HTN virus RdRp endonuclease domain is a particularly appealing approach for drug discovery against this virus. This RdRp endonuclease domain of the HTN virus has a metal-dependent catalytic activity. We targeted this metal-dependent enzymatic activity to identify inhibitors that can bind and disrupt this endonuclease enzyme activity using in-silico approaches i.e., molecular docking, molecular dynamics simulation, predicted absorption, distribution, metabolism, excretion, toxicity (ADMET) and drug-likeness studies. The docking studies showed that peramivir, and ingavirin compounds can effectively bind with the manganese ions and engage with other active site residues of this protein. Molecular simulations also showed stable binding of these ligands with the active site of HTN RdRp. Simulation analysis showed that they were in constant contact with the active site manganese ions and amino acid residues of the HTN virus endonuclease domain. This study will help in better understanding the HTN and related viruses.

Hybrid Control of the DC Microgrid Using Deep Neural Networks and Global Terminal Sliding Mode Control with the Exponential Reaching Law.

The direct current (DC) microgrid is one of the key research areas for our advancement toward carbon-free energy production. In this paper, a two-step controller is designed for the DC microgrid using a combination of the deep neural network (DNN) and exponential reaching law-based global terminal sliding mode control (ERL-GTSMC). The DC microgrid under consideration involves multiple renewable sources (wind, PV) and an energy storage unit (ESU) connected to a 700 V DC bus and a 4-12 kW residential load. The proposed control method eliminates the chattering phenomenon and offers quick reaching time by utilizing the exponential reaching law (ERL). In the two-step control configuration, first, DNNs are used to find maximum power point tracking (MPPT) reference values, and then ERL-based GTSMC is utilized to track the reference values. The real dynamics of energy sources and the DC bus are mathematically modeled, which increases the system's complexity. Through the use of Lyapunov stability criteria, the stability of the control system is examined. The effectiveness of the suggested hybrid control algorithm has been examined using MATLAB simulations. The proposed framework has been compared to traditional sliding mode control and terminal sliding mode control to showcase its superiority and robustness. Experimental tests based on the hardware-in-the-loop (HIL) setup are then conducted using 32-bit TMS320F28379D microcontrollers. Both MATLAB and HIL results show strong performance under a range of environmental circumstances and system uncertainties.

Bridging the resources gap: deep learning for fluorescein angiography and optical coherence tomography macular thickness map image translation.

BACKGROUND: To assess the ability of the pix2pix generative adversarial network (pix2pix GAN) to synthesize clinically useful optical coherence tomography (OCT) color-coded macular thickness maps based on a modest-sized original fluorescein angiography (FA) dataset and the reverse, to be used as a plausible alternative to either imaging technique in patients with diabetic macular edema (DME). METHODS: Original images of 1,195 eyes of 708 nonconsecutive diabetic patients with or without DME were retrospectively analyzed. OCT macular thickness maps and corresponding FA images were preprocessed for use in training and testing the proposed pix2pix GAN. The best quality synthesized images using the test set were selected based on the Fréchet inception distance score, and their quality was studied subjectively by image readers and objectively by calculating the peak signal-to-noise ratio, structural similarity index, and Hamming distance. We also used original and synthesized images in a trained deep convolutional neural network (DCNN) to plot the difference between synthesized images and their ground-truth analogues and calculate the learned perceptual image patch similarity metric. RESULTS: The pix2pix GAN-synthesized images showed plausible subjectively and objectively assessed quality, which can provide a clinically useful alternative to either image modality. CONCLUSION: Using the pix2pix GAN to synthesize mutually dependent OCT color-coded macular thickness maps or FA images can overcome issues related to machine unavailability or clinical situations that preclude the performance of either imaging technique. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05105620, November 2021. "Retrospectively registered".

Identification and Inhibition of the Druggable Allosteric Site of SARS-CoV-2 NSP10/NSP16 Methyltransferase through Computational Approaches.

Since its emergence in early 2019, the respiratory infectious virus, SARS-CoV-2, has ravaged the health of millions of people globally and has affected almost every sphere of life. Many efforts are being made to combat the COVID-19 pandemic's emerging and recurrent waves caused by its evolving and more infectious variants. As a result, novel and unexpected targets for SARS-CoV-2 have been considered for drug discovery. 2'-O-Methyltransferase (nsp10/nsp16) is a significant and appealing target in the SARS-CoV-2 life cycle because it protects viral RNA from the host degradative enzymes via a cap formation process. In this work, we propose prospective allosteric inhibitors that target the allosteric site, SARS-CoV-2 MTase. Four drug libraries containing ~119,483 compounds were screened against the allosteric site of SARS-CoV-2 MTase identified in our research. The identified best compounds exhibited robust molecular interactions and alloscore-score rankings with the allosteric site of SARS-CoV-2 MTase. Moreover, to further assess the dynamic stability of these compounds (CHEMBL2229121, ZINC000009464451, SPECS AK-91811684151, NCI-ID = 715319), a 100 ns molecular dynamics simulation, along with its holo-form, was performed to provide insights on the dynamic nature of these allosteric inhibitors at the allosteric site of the SARS-CoV-2 MTase. Additionally, investigations of MM-GBSA binding free energies revealed a good perspective for these allosteric inhibitor-enzyme complexes, indicating their robust antagonistic action on SARS-CoV-2 (nsp10/nsp16) methyltransferase. We conclude that these allosteric repressive agents should be further evaluated through investigational assessments in order to combat the proliferation of SARS-CoV-2.

Novel Copper Oxide Bio-Nanocrystals to Target Outer Membrane Lectin of Vancomycin-Resistant Enterococcus faecium (VREfm): In Silico, Bioavailability, Antimicrobial, and Anticancer Potential.

In present study, we used Olea europaea leaf extract to biosynthesize in situ Copper Oxide nanocrystals (CuO @OVLe NCs) with powerful antibacterial and anti-cancer capabilities. Physio-chemical analyses, such as UV/Vis, FTIR, XRD, EDX, SEM, and TEM, were applied to characterize CuO @OVLe NCs. The UV/Vis spectrum demonstrated a strong peak at 345 nm. Furthermore, FTIR, XRD, and EDX validated the coating operation's contact with colloidal CuO @OVLe NCs. According to TEM and SEM analyses, CuO @OVLe NCs exhibited a spherical shape and uniform distribution of size with aggregation, for an average size of ~75 nm. The nanoparticles demonstrated a considerable antibacterial effect against E. faecium bacterial growth, as well as an increased inhibition rate in a dose-dependent manner on the MCF-7, PC3, and HpeG2 cancer cell lines and a decreased inhibition rate on WRL-68. Molecular docking and MD simulation were used to demonstrate the high binding affinity of a ligand (Oleuropein) toward the lectin receptor complex of the outer membrane to vancomycin-resistant E. faecium (VREfm) via amino acids (Leu 195, Thr 288, His 165, and Ser 196). Hence, our results expand the accessibility of OVLe's bioactive components as a promising natural source for the manufacture of physiologically active components and the creation of green biosynthesis of metal nanocrystals.

Antifungal and antibiofilm activities of bee venom loaded on chitosan nanoparticles: a novel approach for combating fungal human pathogens.

The prevalence of opportunistic human fungal pathogens is increasing worldwide, and antimicrobial resistance is one of the greatest medical challenges the world faces. Therefore, this study aimed to develop a novel agent to control fungal pathogens. The honeybee products (honey, royal jelly, propolis, bee bread, and bee venom) were screened against unicellular fungal (UCF) pathogens (Cryptococcus neoformans, Kodamaea ohmeri, and Candida albicans) and the bee venom was only exhibited an inhibitory effect against them. The protein contents of crude bee venom were separated using the gel filtration technique into eight fractions which were visualized on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to confirm the presence of five bands with molecular weights of 65, 43, 21, 15, and 3 KDa. Bee venom (BV) of Apis mellifera loaded chitosan nanoparticles were prepared by the ionotropic gelation method. The encapsulation efficiency%, average size, zeta potentials, and surface appearance by Transmission electron microscope (TEM) were evaluated for the prepared nanoparticles. The minimum inhibitory concentration (MIC) of crude BV and BV loaded chitosan nanoparticles (BV-CNPs) was evaluated against the offer mentioned UCF where the MIC values of crude BV were 6.25, 3.12 & 6.25 while MIC values in the case of BV-CNPs were decreased to 3.12, 3.12 & 1.56 mg/ml against C. neoformans, K. ohmeri and C. albicans, respectively. Also, the results showed that BV-CNPs suppressed the biofilm formation as well as yeast to hyphal transition formed by the examined UCF. These results revealed that BV-CNPs are a promising natural compound for fungal pathogens treatment.

Co-delivery of hesperidin and clarithromycin in a nanostructured lipid carrier for the eradication of Helicobacter pylori in vitro.

Effective and precise eradication of Helicobacter pylori (H. pylori) is the most promising approach to avoid H. pylori-related gastrointestinal disorders. The present study was conducted to demonstrate the efficacy of the co-delivery of hesperidin (Hesp) and clarithromycin (CLR) in nanostructured lipid carriers (NLCs) against H. pylori. We have produced a new delivery system by combining bioflavonoid Hesp and CLR NLCs to address the failure in single antibiotic therapies. Briefly, a blend of solid lipid, liquid lipid, and surfactant was used. Homogeneous NLCs with all the formulations showed a nano size and surface-negative charge and presented high in vitro stability and slow release of the drug even after 24 h. Bioimaging studies by scanning electron microscopy, transmission electron microscopy, and imaging flow cytometry indicated that NLCs interacted with the membrane by adhering to the outer cell membrane and disrupted the membrane that resulted in the leakage of cytoplasmic contents. The prepared NLCs provide sustained and controlled drug release that can be used to increase the rate of H. pylori eradication.

Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition.

The COVID-19 pandemic has caused millions of fatalities since 2019. Despite the availability of vaccines for this disease, new strains are causing rapid ailment and are a continuous threat to vaccine efficacy. Here, molecular docking and simulations identify strong inhibitors of the allosteric site of the SARS-CoV-2 virus RNA dependent RNA polymerase (RdRp). More than one hundred different flavonoids were docked with the SARS-CoV-2 RdRp allosteric site through computational screening. The three top hits were Naringoside, Myricetin and Aureusidin 4,6-diglucoside. Simulation analyses confirmed that they are in constant contact during the simulation time course and have strong association with the enzyme's allosteric site. Absorption, distribution, metabolism, excretion and toxicity (ADMET) data provided medicinal information of these top three hits. They had good human intestinal absorption (HIA) concentrations and were non-toxic. Due to high mutation rates in the active sites of the viral enzyme, these new allosteric site inhibitors offer opportunities to drug SARS-CoV-2 RdRp. These results provide new information for the design of novel allosteric inhibitors against SARS-CoV-2 RdRp.

Instantaneous oxidation of levofloxacin as toxic pharmaceutical residuals in water using clay nanotubes decorated by ZnO (ZnO/KNTs) as a novel photocatalyst under visible light source.

Kaolinite nanotubes were synthesized by a simple scrolling process and decorated by ZnO nanoparticles as a novel nanocomposite (ZnO/KNTs). The synthetic ZnO/KNTs composite was characterized as an effective photocatalyst in the oxidation of levofloxacin pharmaceutical residuals in the water resources. The composite displays a surface area of 95.4 m2/g, average pore diameter of 5.8 nm, and bandgap energy of 2.12 eV. It is of high catalytic activity in the oxidation of levofloxacin in the presence of visible light source. The complete oxidation for 10 mg/L of levofloxacin was recognized after 55 min, 45 min, and 30 min with applying 30 mg, 40 mg, and 50 mg of ZnO/KNTs as catalyst dosage, respectively. Additionally, it achieved complete oxidation for 20 mg/L and 30 mg/L of levofloxacin after 45 min and 75 min, respectively using 50 mg as catalyst dosage. The degradation efficiency was confirmed by detecting the residual TOC after the treatment tests and the formed intermediate compounds were identified to suggest the degradation pathways. In addition to the oxidation pathway, the mechanism was evaluated based on the active trapping tests that proved the dominance of hydroxyl radicals as the essential active species. Finally, the ZnO/KNTs composite is of promising recyclability properties and achieved better results than several studied photocatalysts in literature.

Three new flavonol glycosides from Suaeda maritima.

Three new flavonol glycosides isolated from the 70% methanol extract of Suaeda maritima (Chenopodiaceae) were characterized based on spectroscopic and chemical methods as quercetin 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-ß-d-glucopyranosyl(1″″' â†’ 2″″)-glucopyranoside, kaempferol 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-ß-d-glucopyranosyl(1″″' â†’ 2″″)-glucopyranoside, and kaempferol 3-O-α-l-rhamnopyranosyl(1″' â†’ 6″)-ß-d-galactopyranoside-7-O-(2″″'-O-trans-feruloyl)-ß-d-glucopyranosyl-(1″″' â†’ 2″″)-ß-d-glucopyranoside. In addition, four known compounds, namely, quercetin and kaempferol, methyl cis, trans-ferulate, and methyl trans-ferulate were identified. The plant extract and these compounds showed cytotoxic activity against the human tumor cell lines MCF7, HCT116, and HEPG2.

Multiscale tribology analysis of MHD hybrid nanofluid flow over a curved stretching surface.

In this study, we investigate the interactions of a hybrid nanofluid on a curved surface that is being stretched. The magnetic field is perpendicular to the flow and interacts with a mixture of molybdenum disulfide and argentum nanoparticles suspended in pure water, forming a hybrid nanomaterial. Our investigation considers heat transport analysis under different conditions, such as magnetohydrodynamic, Darcy-Forchheimer porous medium flow, Joule heating, and a convective boundary condition. We employ numerical and statistical methods to study the problem's intricacies comprehensively. Our findings indicate that Darcy-Forchheimer flow includes viscous and inertial forces, which results in higher flow rates and reduced skin friction. Additionally, the convective boundary condition leads to uniform temperature distribution within the hybrid material due to rapid internal heat transfer relative to surface resistance, significantly increasing the heat transfer rate.

Comparative analysis of GAN-based fusion deep neural models for fake face detection.

Fake face identity is a serious, potentially fatal issue that affects every industry from the banking and finance industry to the military and mission-critical applications. This is where the proposed system offers artificial intelligence (AI)-based supported fake face detection. The models were trained on an extensive dataset of real and fake face images, incorporating steps like sampling, preprocessing, pooling, normalization, vectorization, batch processing and model training, testing-, and classification via output activation. The proposed work performs the comparative analysis of the three fusion models, which can be integrated with Generative Adversarial Networks (GAN) based on the performance evaluation. The Model-3, which contains the combination of DenseNet-201+ResNet-102+Xception, offers the highest accuracy of 0.9797, and the Model-2 with the combination of DenseNet-201+ResNet-50+Inception V3 offers the lowest loss value of 0.1146; both are suitable for the GAN integration. Additionally, the Model-1 performs admirably, with an accuracy of 0.9542 and a loss value of 0.1416. A second dataset was also tested where the proposed Model-3 provided maximum accuracy of 86.42% with a minimum loss of 0.4054.

Entropy analysis of MHD hybrid nanoparticles with OHAM considering viscous dissipation and thermal radiation.

This research explores the 3-D flow characteristics, entropy generation and heat transmission behavior of nanofluids consisting of copper and titanium in water as they flow across a bidirectional apparent, while considering the influence of magneto-hydrodynamics. The thermophysical properties of nanofluids are taken advantage of utilizing the Tiwari and Das demonstrate. The concept of the boundary layer has facilitated the comprehension of the physical ideas derived from it. By applying requisite transformations, the connected intricate sets of partial differential equation have been converted into ordinary differential equation. The modified model is calculated employing the widely recognized technique known as OHAM by using Mathematica program BVPh2.0 Software. For different dimensionless parameters computational and graphical investigations have been performed. It is notice that as fluid parameters change, they exhibit distinct responses in comparison to the temperature, velocity profiles and entropy generation. The results show that velocity profile rise with greater estimates of the magnetic parameter and the rate of entropy formation. Furthermore, thermal profiles become less significant as Eckert and Prandtl numbers increase.

Prostate cancer across four countries in the Middle East: a multi-centre, observational, retrospective and prognostic study.

Prostate cancer (PC) is the second most prevalent cancer in males, with a steadily increasing incidence in the Middle East (ME). The aim of this study was to capture real-world data on the characteristics, disease progression, and treatment patterns among PC patients in the ME. This was a retrospective, observational, multi-centre study conducted across ten hospitals/research centers in Lebanon, Kingdom of Saudi Arabia, Iraq and Kuwait. Data were abstracted from medical records of 615 male patients who were diagnosed with PC between January 2012 and the site initiation date (December 2018-May 2019) and received at least one PC treatment/intervention. The observation period ranged between 84 and 88 months. Data were collected on demographics, clinical characteristics, time to progression to the subsequent clinical state or therapy (progression from localised/locally advanced PC to castration and to metastatic PC (metastatic castration-sensitive PC (mCSPC) or metastatic castration-resistant PC (mCRPC)), progression from mCSPC to mCRPC, and mCRPC patients' progression to first subsequent line of therapy), treatment patterns, and mortality. Most patients had localised/locally advanced PC (57.7%), followed by mCSPC (37.4%), and mCRPC (4.1%) at the time of inclusion in the study. Most patients were at tumours, nodes and metastases (TNM) stage IIIa (40.1%) or TNM stage IVb (27.8%) at study entry. Median time to metastatic disease, castration-resistance and next line therapy was 84 months (95% CI: 68-84), 41 months (95% CI: 30-56) and 7 months (95% CI: 0-41), respectively. The mortality rate was 3.6%. Disease progression was most common among patients with mCSPC (35.1%) or mCRPC (14.8%), and treatment discontinuation was most common among patients with mCRPC (36.6% treatments discontinued). The results show that most patients were at an advanced TNM stage at study entry, suggestive of a lack of awareness regarding PC. Disease progression was most common among patients with metastatic disease, reflecting the challenge of treating metastatic disease and highlighting the need for novel treatments.

Bee chitosan nanoparticles loaded with apitoxin as a novel approach to eradication of common human bacterial, fungal pathogens and treating cancer.

Antimicrobial resistance is one of the largest medical challenges because of the rising frequency of opportunistic human microbial infections across the globe. This study aimed to extract chitosan from the exoskeletons of dead bees and load it with bee venom (commercially available as Apitoxin [Api]). Then, the ionotropic gelation method would be used to form nanoparticles that could be a novel drug-delivery system that might eradicate eight common human pathogens (i.e., two fungal and six bacteria strains). It might also be used to treat the human colon cancer cell line (Caco2 ATCC ATP-37) and human liver cancer cell line (HepG2ATCC HB-8065) cancer cell lines. The x-ray diffraction (XRD), Fourier transform infrared (FTIR), and dynamic light scattering (DLS) properties, ζ-potentials, and surface appearances of the nanoparticles were evaluated by transmission electron microscopy (TEM). FTIR and XRD validated that the Api was successfully encapsulated in the chitosan nanoparticles (ChB NPs). According to the TEM, the ChB NPs and the ChB NPs loaded with Apitoxin (Api@ChB NPs) had a spherical shape and uniform size distribution, with non-aggregation, for an average size of approximately 182 and 274 ± 3.8 nm, respectively, and their Zeta potential values were 37.8 ± 1.2 mV and - 10.9 mV, respectively. The Api@ChB NPs had the greatest inhibitory effect against all tested strains compared with the ChB NPs and Api alone. The minimum inhibitory concentrations (MICs) of the Api, ChB NPs, and Api@ChB NPs were evaluated against the offer mentioned colony forming units (CFU/mL), and their lowest MIC values were 30, 25, and 12.5 µg mL-1, respectively, against Enterococcus faecalis. Identifiable morphological features of apoptosis were observed by 3 T3 Phototox software after Api@ChB NPs had been used to treat the normal Vero ATCC CCL-81, Caco2 ATCC ATP-37, and HepG2 ATCC HB-8065 cancer cell lines for 24 h. The morphological changes were clear in a concentration-dependent manner, and the ability of the cells was 250 to 500 µg mL-1. These results revealed that Api@ChB NPs may be a promising natural nanotreatment for common human pathogens.

Targeted potent antimicrobial and antitumor oxygen-heterocyclic-based pyran analogues: synthesis and computational studies.

The process of creating a series of 3-amino-1-aryl-8-methoxy-1H-benzo[f]chromene-2-carbonitriles (4a-q) involved reacting 6-methoxynaphthalen-2-ol (1), the appropriate aromatic aldehydes (2a-q), and malononitrile (3) in an absolute ethanol/piperidine solution under Ultrasonic irradiation. However, the attempt to create 3-amino-1-aryl-1H-benzo[f]chromene-2,8-dicarbonitrile (6a, d, e) was unsuccessful when 6-cyanonaphthalen-2-ol (5) was stirred at room temperature, reflux, Microwave irradiation, or Ultrasonic irradiation. In addition, the target molecules were screened against Staphylococcus aureus (MRSA), Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli and Klebsiella pneumonia, as well as a panel of three human cancer cells lines such as MCF-7, HCT-116, HepG-2 and two normal cell lines HFL-1 and WI-38. The obtained results confirmed that the pyran derivatives (4 m, i, k) which have a double chlorine at 3,4/2,3/2,5-positions, a single halogen atom 3-Cl/4-Br (4c, e) and a double bromine at 3,5-positions with a single methoxy group at 2-position (4n), of phenyl ring, and, to a lesser extent, other pyran derivatives with monoihalogenated (4a, b, d, f), dihalogenated (4 g, h, j, l) or trisubstituent phenyl ring (4o, p, q). Furthermore, compounds 4b-e, g, i, j, m, and n showed negligible activity against the two normal cell lines, HFL-1 and WI-38. Moreover, compound 4 g exhibited the strongest antimicrobial activity among the other pyran derivatives (4a-f, g-q) when compared to Ciprofloxacin. The MIC was assessed and screened for compound 4 g, revealing bactericidal effects. Lastly, SAR and molecular docking were studied.