Investigating the emigration intention of health care workers: A cross-sectional study.

AIMS: To (1) explore the intramigration experience of HCWs within Nigeria, (2) explore the migration intention of health care workers (HCWs) in Nigeria and (3) identify the predictors of migration intention among HCWs in Nigeria. DESIGN: Cross-sectional study. METHODS: The online survey was used to collect data from 513 HCWs in Nigeria between May and June 2023. Crude and adjusted logistic regression were used to identify factors associated with emigration intention. Analyses were performed on SPSS version 26 at a 95% confidence interval. RESULTS: The study found that 34.4% had intramigration experience, and the rate of intention to emigrate to work in another country was 80.1%. The United Kingdom was the most preferred destination (109 HCWs), followed by Canada (92 HCWs) and the United States (82 HCWs). At the multivariate level, emigration intention was associated with the experience of burnout and duration of practice as a HCW. Nurses had higher emigration intentions than medical doctors. CONCLUSIONS: Many HCWs in Nigeria appear to have emigration intent, and nurses are more likely to be willing to migrate than doctors. The Nigerian government may want to explore strategies to reverse the emigration intent of the HCWs in Nigeria.

Advancing safe mobility: A global analysis of research trends in safe route planning.

Safe route planning has become an increasingly important area of research in recent years due to growing concerns about pedestrian and traffic safety, rising traffic volumes and densities in urban areas, and advancements in smart vehicle and transportation technologies. This study conducted a bibliometric analysis of publications on safe route planning retrieved from the Web of Science database between January 2000 and January 2023 to understand the state of the field. A total of 1546 publications authored by 5423 researchers from 84 countries were analyzed. The findings identified the United States, China, India, South Korea, and Spain as the most productive countries, while the University of North Carolina emerged as the most productive organization. Engineering, computer science, transportation, public health, and automation were revealed to be the dominant initial research areas, although interest grew from other domains like urban planning and the environment over time. Analysis of publications by year showed a steady rise in output starting from 2008. Notable influential publications and highly cited authors in the field were also identified. Several research themes and terms like path planning, safety, walking, and route to school were highlighted through keyword analysis. This study provided novel insights into the evolving international landscape, topics, and influential contributors in safe route planning research over the past two decades. Limitations in database coverage and analytical techniques necessitate future work to enhance understanding in this critical domain.

Identification of potent EGFR-TKD inhibitors from NPACT database through combined computational approaches.

Cancer is the world's second leading cause of death, and there are no approved herbal therapies. The epidermal growth factor receptor tyrosine kinase (EGFR-TK) receptor is a transmembrane protein with eight domains that is found in almost every cancer type and plays an important role in abnormal cell cellular function and causes malignant outcomes. The current study aimed to virtually screen phytochemicals from the NPACT database against EGFR-TKD and also to identify potential inhibitors of this transmembrane protein among plant candidates for anticancer drug development. The docking scores of the chosen phytochemicals were compared with the control (erlotinib). Kurarinone, (2S)-2-methoxykurarnione, and Sophoraflavanone-G exhibited a stronger binding affinity of -18.102 kcal/mol, -14.243 kcal/mol, and -13.759 kcal/mol than erlotinib -12.783 kcal/mol. Moreover, several online search engines were used to predict ADME and toxicity. The drug-likeness of selected phytochemicals was higher than the reference (erlotinib). A 100 ns molecular dynamic (MD) simulation was also applied to the docked conformations to examine the stability and molecular mechanics of protein-ligand interactions. Furthermore, the calculated molecular mechanics Poisson Boltzmann surface area energy of (2S)-2-methoxykurarnione was found to be -129.555 ± 0.512 kJ/mol, which approximately corresponds to the free energy of the reference molecule -130.595 ± 0.908 kJ/mol. We identify phytoconstituents present in Sophora flavescens from the NPACT database, providing key insights into tyrosine kinase inhibition and may serve as better chemotherapeutic agents. Experimental validation is required to determine the anti-EGFR potency of the potent lead molecules discussed in this study.Communicated by Ramaswamy H. Sarma.

Antibacterial Potential of a Novel Peptide from the Consensus Sequence of Dermaseptin Related Peptides Secreted by Agalychnis annae.

BACKGROUND: The consistently increasing reports of bacterial resistance and the reemergence of bacterial epidemics have inspired the health and scientific community to discover new molecules with antibacterial potential continuously. Frog-skin secretions constitute bioactive compounds essential for finding new biopharmaceuticals. The exact antibacterial characterization of dermaseptin related peptides derived from Agalychnis annae, is limited. The resemblance in their conserved and functionally linked genomes indicates an unprecedented opportunity to obtain novel bioactive compounds. OBJECTIVE: In this study, we derived a novel peptide sequence and determined its antibacterial potentials. METHODS: Consensus sequence strategy was used to design the novel and active antibacterial peptide named 'AGAAN' from skin secretions of Agalychnis annae. The in-vitro activities of the novel peptide against some bacterial strains were investigated. Time kill studies, DNA retardation, cytotoxicity, betagalactosidase, and molecular computational studies were conducted. RESULTS: AGAAN inhibited P. aeruginosa, E. faecalis, and S. typhimurium at 20 µM concentration. E. coli and S. aureus were inhibited at 25 µM, and lastly, B. subtilis at 50 µM. Kinetics of inactivation against exponential and stationary growing bacteria was found to be rapid within 1-5 hours of peptide exposure, depending on time and concentration. The peptide displayed weak hemolytic activity between 0.01%-7.31% at the antibacterial concentrations. AGAAN efficiently induced bacterial membrane damage with subsequent cell lysis. The peptide's DNA binding shows that it also targets intracellular DNA by retarding its movement. Our in-silico molecular docking analysis displayed a strong affinity to the bacterial cytoplasmic membrane. CONCLUSION: AGAAN exhibits potential antibacterial properties that could be used to combat bacterial resistance.

Effect of N-terminal modification on the mode of action between the Xyn11A and Xylotetraose.

The purpose of this study was to gain an insight into the effects of mutation-induced binding pocket tilting of the Xyn11A xylanase from Bacillus firmus K-1 in producing a unique hydrolysis characteristic. In this study, the wildtype Xyn11A and its K40L mutant were compared for their hydrolysis patterns on beechwood xylan and xylooligosaccharides of sizes 2 to 6. According to our thin-layer chromatography experiment, the K40L mutant produced a larger amount of xylotetraose leftover than the wildtype. Kinetic determination of the WT and K40L mutant suggested that the higher X4 leftover on TLC was reflected in the decreasing catalytic efficiency (kcat/Km) between enzyme and X4. The mechanisms underlying this efficiency loss were examined through atomistic molecular dynamics (MD) simulations. The MD trajectory analysis showed that the mutation-induced binding pocket tilting resulted in an additional hydrophobic contact between the reducing end of X4 and Trp128. Meanwhile, the interactions between the non-reducing end and the Arg112 residue near the active site became lost, which could decrease the catalytic efficiency. This work suggested that the protein engineering to fine-tune the hydrolysis pattern for some desired xylooligosaccharide products was possible.

Effects of oligolignol sizes and binding modes on a GH11 xylanase inhibition revealed by molecular modeling techniques.

Lignin and phenolic compounds have been shown as the main recalcitrance for biomass decomposition, as they inhibit a number of lignocellulose-degrading enzymes. Understanding the inhibition mechanisms and energetic competitions with the native substrate is essential for the development of lignin resistive enzymes. In this study, atomistic detail of the size-dependent effects and binding modes of monomeric coniferyl alcohol, dimeric oligolignol, and tetrameric oligolignol made from coniferyl alcohols on the GH11 xylanase from Bacillus firmus strain K-1 was investigated by using molecular docking and atomistic molecular dynamics (MD) simulations. From the MD simulation results on the docked conformation of oligolignol binding within the "Cleft" and the "N-terminal," changes were observed both for protein conformations and positional binding of ligands, as binding with "Thumb" regions was found for all oligolignin models. Moreover, the uniquely stable "N-terminal" binding of the coniferyl alcohol monomer had no effect on the highly fluctuated Thumb region, showing no sign of inhibitory effect, and was in good agreement with recent studies. However, the inhibitory effect of oligolignols was size dependent, as the estimated binding energy of the tetrameric oligolignol became stronger than that of the xylohexaose substrate, and the important binding residues were identified for future protein engineering attempts to enhance the lignin resistivity of GH11. Graphical Abstract Size-dependent binding modes of coniferyl alcohol monomers (upper panels) and the dimers (lower panels). Uniquely stable "N-terminal" binding of the monomer is shown to have no effect on the binding pocket, and hence no sign of inhibition, which was in good agreement with some recent studies.

Synergistic effects between the additions of a disulphide bridge and an N-terminal hydrophobic sidechain on the binding pocket tilting and enhanced Xyn11A activity.

Synergistic effect of distal site-directed mutations and molecular mechanisms on the enhanced thermostability of GH11 xylanase from B. firmus Strain K-1 (xyn11A) was investigated through enzyme activity assays and atomistic molecular dynamics (MD) simulation. From the experiment, single N-terminal leucine substitution at K40L caused a significant drop in enzymatic activity. However, the addition of a disulphide bond at S100C/N147C, along with the K40L mutation enhanced the enzymatic activity at room temperature. Molecular mechanisms on the improvement of enzymatic activity were addressed through atomistic molecular dynamics (MD) simulations of enzyme-substrate complexes. Conformational analysis of the right-hand-shaped GH11 protein structures showed that K40L mutation 'tilted' the Palm region away from the Pinky finger at N-terminus and S100C/N147C tilted the Palm region towards the Pinky finger at N-terminus, which destabilized the binding complexes. The extended hydrophobic cluster formed within the K40L/S100C/N147C mutant stabilized the loops associated with the N-terminus and the Thumb region, which facilitated substrate binding and corresponded to the enhanced activity. This proposed mechanism could serve as a scheme for protein engineering to enhance enzymatic activity of GH11 enzymes at low temperatures.

Optimization of Bromelain-Aided Production of Angiotensin I-Converting Enzyme Inhibitory Hydrolysates from Stone Fish Using Response Surface Methodology.

The stone fish is an under-utilized sea cucumber with many nutritional and ethno-medicinal values. This study aimed to establish the conditions for its optimum hydrolysis with bromelain to generate angiotensin I-converting enzyme (ACE)-inhibitory hydrolysates. Response surface methodology (RSM) based on a central composite design was used to model and optimize the degree of hydrolysis (DH) and ACE-inhibitory activity. Process conditions including pH (4-7), temperature (40-70 °C), enzyme/substrate (E/S) ratio (0.5%-2%) and time (30-360 min) were used. A pH of 7.0, temperature of 40 °C, E/S ratio of 2% and time of 240 min were determined using a response surface model as the optimum levels to obtain the maximum ACE-inhibitory activity of 84.26% at 44.59% degree of hydrolysis. Hence, RSM can serve as an effective approach in the design of experiments to improve the antihypertensive effect of stone fish hydrolysates, which can thus be used as a value-added ingredient for various applications in the functional foods industries.