Theoretical study of the photoisomerization of 1,2-bispyrazinyl-ethylene and the halogen ion salts of 1-Pyrazinyl-2-(4'-methylpyrazinyl)ethylene.

CONTEXT: It has been reported that photoexcitation of azastilbene compounds like E-1,2-bispyrazinyl-ethylene (bpe) can undergo E → Z photoisomerization of its quaternary salts via the excited triplet state. However, experimentally it is possible to get low fluorescence and photoisomerisation quantum yields in a state with higher internal conversion than intersystem crossing. We modelled bpe and its methylated derivative (bpeMe), as well as its quaternary halogen salts (bpeMeX with X = F-, Cl-, Br- and I-) to study levels of fluorescence, phosphorescence and excited state potential energy surfaces (PES). Results support experimental observations of molecules where the anion of a salt is an efficient electron donor, that molecules with weak electron-donating anions like Cl- to give increased fluorescence and photoisomerization, as compared to molecules with stronger electron-donating anions like I-, which are dominated by competing electron transfer. The fluorescence of bpeMeF and bpeMeCl was found to be stronger than bpeMeBr and bpeMeI. A deep well in the triplet excited state of bpeMeI is considered responsible for the decreased photoisomerization, compared to what was experimentally observed for bpeMeCl. Uniquely, the bpeMeI molecule is characterised by near-zero splitting of the s1 and t1 excited states that can enhance charge transfer. The quaternary salt of bpeMe with stronger electron-donating Br- anion was observed to undergo fluorescence and phosphorescence at much lower energy compared to those with weak electron-donating F- and Cl- anions. This research shows how to control the excited state fluorescence, phosphorescence and isomerization of quaternary halogen salts of methyl derivatives of 1,2-bispyrazinyl-ethylene, which aids experimental design where excited state isomerization is considered. METHODS: Geometry optimization, molecular electrostatic potential (MESP), and time dependent density functional theory (TDDFT) calculations were conducted utilizing Gaussian 16 with the B3LYP functional and the 6-31 + G(d,p) basis set. The minimum energy path (MEP) for the E to Z isomerization of the molecules was established employing the Nudged-Elastic-Band (NEB) method, implemented in Orca 4.2. Precise energies of the E → Z isomerization reaction path were determined employing CASSCF and a more accurate multireference method, NEVPT2.

Isolation, characterization and modulatory potentials of ß-stigmasterol, ergosterol and xylopic acid from Anchomanes difformis on mitochondrial permeability transition pore in vitro.

Objective: Secondary metabolites and polyphenolic compounds from medicinal plants have been demonstrated to have multiple biological functions with promising research and development prospects. This study examined the effect of ß-stigmasterol (with ergosterol) and xylopic acid isolated from Anchomanes difformis on liver mitochondrial permeability transition pore (mPTP). Methods: The compounds were isolated by vacuum liquid chromatography. Mitochondrial swelling was assessed as changes in absorbance under succinate-energized conditions. Results: 1H and 13C NMR spectroscopic elucidation of the isolates affirmed the presence of ß-stigmasterol with ergosterol (1:0.3) and xylopic acid. The isolates reversed the increase in lipid peroxidation and inhibited the opening of mitochondrial permeability transition pores caused by calcium and glucose. Pharmacological inhibition of mPTP offers a promising therapeutic target for the treatment of mitochondrial-associated disorders. Conclusion: Reduction in the activity of calcium ATPase and the expression of Caspase-3 and -9 were observed, suggesting that they could play a role in protecting physicochemical properties of membrane bilayers from free radical-induced severe cellular damage and be useful in the management of diseases where much apoptosis occurs.

Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against Mycobacterium ulcerans.

Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium Mycobacterium ulcerans and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and M. ulcerans-specific vaccines in animal models. However, there are currently no clinically accepted vaccines to prevent M. ulcerans infection. The aim of this study was to identify T-cell and B-cell epitopes from the mycobacterial membrane protein large (MmpL) proteins of M. ulcerans. These epitopes were analysed for properties including antigenicity, immunogenicity, non-allergenicity, non-toxicity, population coverage and the potential to induce cytokines. The final 8 CD8+, 12 CD4+ T-cell and 5 B-cell epitopes were antigenic, non-allergenic and non-toxic. The estimated global population coverage of the CD8+ and CD4+ epitopes was 97.71%. These epitopes were used to construct five multi-epitope vaccine constructs with different adjuvants and linker combinations. The constructs underwent further structural analyses and refinement. The constructs were then docked with Toll-like receptors. Three of the successfully docked complexes were structurally analysed. Two of the docked complexes successfully underwent molecular dynamics simulations (MDS) and post-MDS analysis. The complexes generated were found to be stable. However, experimental validation of the complexes is required.

Burnout: A predictor of oral health impact profile among Nigerian early career doctors.

There have been reported association of oral health disorders with burnout, stress, and mental health. Arguably, with these reported associations, and the current prevalence of burnout amongst Nigerian doctors, exploring the role of burnout on oral health amongst Nigerian doctors is timely. This study aims to determine the relationship between burnout and oral health-related quality of life amongst Early Career Doctors (ECDs) in Nigeria, while also identifying the role other possible predictors plays in this relationship. This was a cross-sectional study conducted amongst Nigerian ECDs as part of Challenges of Residency Training in Nigeria (CHARTING) II project. A total of 632 ECDs were recruited across thirty-one tertiary hospitals in the 6 geopolitical zones of the country using a multistage cluster sampling technique. A self-administered paper-based semi-structured questionnaire was given to each participant that consented. The tools used to assess burnout and Oral health-related quality of life (OHRQoL) were Copenhagen Burnout Inventory (CBI) and Oral Health Impact Profile (OHIP-14) respectively. Independent samples T-test, ANOVA and Multiple linear regression were used to draw inferences from the data collected. Overall mean OHIP-14 score of all participants was 11.12 (±9.23). The scores for the 3 dimensions of burnout were below 50% with CBI-Personal Burnout having the highest score of 49.96 (±19.15). Significant positive correlations (p < 0.001) were found between OHIP-14 and all the dimensions of burnout, as the burnout scores were increasing, there was a corresponding increase in the OHIP scores thus poorer OHRQoL. The regression model shows that the predictors of OHIP were CBI-PB (p = 0.003), use of fluoride paste (p = 0.039), use of tobacco (p = 0.005) and being a denture user (p = 0.047). This study shows a positive correlation between burnout and OHIP of ECDs. We found that as burnout was increasing, OHIP increased thus implying poorer oral health related quality of life amongst ECDs. The use of fluoride toothpaste, tobacco and denture are other factors we found that could affect the OHIP of ECDs.

Screening of apical membrane antigen-1 (AMA1), dense granule protein-7 (GRA7) and rhoptry protein-16 (ROP16) antigens for a potential vaccine candidate against Toxoplasma gondii for chickens.

Toxoplasmosis is a zoonotic disease caused by the protozoan parasite, Toxoplasma gondii known to infect almost all animals, including birds and humans globally. This disease has impacted the livestock industry and public health, where infection of domestic animals increases the zoonotic risk of transmission of infection to humans, threatening public health. Hence the need to discover novel and safe vaccines to fight against toxoplasmosis. In the current study, a novel multiepitope vaccine was designed using immunoinformatics techniques targeting T. gondii AMA1, GRA7 and ROP16 antigens, consisting of antigenic, immunogenic, non-allergenic and cytokine inducing T-cell (9 CD8+ and 15 CD4+) epitopes and four (4) B-cell epitopes fused together using AAY, KK and GPGPG linkers. The tertiary model of the proposed vaccine was predicted and validated to confirm the structural quality of the vaccine. The designed vaccine was highly antigenic (antigenicity = 0.6645), immunogenic (score = 2.89998), with molecular weight of 73.35 kDa, instability and aliphatic index of 28.70 and 64.10, respectively; and GRAVY of -0.363. The binding interaction, stability and flexibility were assessed with molecular docking and dynamics simulation, which revealed the proposed vaccine to have good structural interaction (binding affinity = -106.882 kcal/mol) and stability when docked with Toll like receptor-4 (TLR4). The results revealed that the Profilin-adjuvanted vaccine is promising, as it predicted induction of enhanced immune responses through the production of cytokines and antibodies critical in blocking host invasion.

Screening for Gestational Diabetes Mellitus: Is There a Need for Early Screening for All Women in Developing Countries?

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with significant adverse pregnancy outcomes. Early diagnosis and treatment have been proven to reduce adverse pregnancy outcomes among women diagnosed with GDM. Current guidelines recommend routine screening for GDM at 24-28 weeks of pregnancy, with early screening offered to those considered high risk. However, risk stratification may not always be helpful for those who would benefit from early screening, especially in non-Western settings. AIM: To determine the need for early screening for GDM among pregnant women attending antenatal clinics in two tertiary hospitals in Nigeria. METHODS: We conducted a cross-sectional study from December 2016 to May 2017. We identified women who presented at the antenatal clinics of the Federal Teaching Hospital Ido-Ekiti and Ekiti State University Teaching Hospital, Ado Ekiti. A total of 270 women who fulfilled the study inclusion criteria were enrolled. The 75 g oral glucose tolerance test was used to screen participants for GDM before 24 weeks and between 24 and 28 weeks for those who screened negative before 24 weeks. Pearson's chi-square test, Fisher's exact test, independent t-test, and Mann-Whitney U test were utilized in the final analysis. RESULTS: The median age of the women in the study was 30 (interquartile range: 27-32) years. Of our study participants, 40 (14.8%) were obese, 27 (10%) had a history of diabetes mellitus in a first-degree relative, and three (1.1%) women had a previous history of GDM. Twenty-one women (7.8%) were diagnosed with GDM, and six (28.6%) were diagnosed before 24 weeks. Women diagnosed with GDM before 24 weeks were older (37 years; interquartile range: 34-37) and more likely to be obese (80.0%). A significant number of these women also had identifiable risk factors for GDM: previous GDM (20.0%), family history of diabetes mellitus in a first-degree relative (80.0%), prior delivery of fetal macrosomia (60.0%), and previous history of congenital fetal anomaly (20.0%). CONCLUSION:  The findings from the present study did not justify universal screening for GDM in all pregnant women. Patients diagnosed before the 24-28 weeks of universal screening are more likely to have significant risk factors for GDM and, therefore, would have been selected for screening based on the risk factor screening.

Identification of potential candidate vaccines against Mycobacterium ulcerans based on the major facilitator superfamily transporter protein.

Buruli ulcer is a neglected tropical disease that is characterized by non-fatal lesion development. The causative agent is Mycobacterium ulcerans (M. ulcerans). There are no known vectors or transmission methods, preventing the development of control methods. There are effective diagnostic techniques and treatment routines; however, several socioeconomic factors may limit patients' abilities to receive these treatments. The Bacillus Calmette-Guérin vaccine developed against tuberculosis has shown limited efficacy, and no conventionally designed vaccines have passed clinical trials. This study aimed to generate a multi-epitope vaccine against M. ulcerans from the major facilitator superfamily transporter protein using an immunoinformatics approach. Twelve M. ulcerans genome assemblies were analyzed, resulting in the identification of 11 CD8+ and 7 CD4+ T-cell epitopes and 2 B-cell epitopes. These conserved epitopes were computationally predicted to be antigenic, immunogenic, non-allergenic, and non-toxic. The CD4+ T-cell epitopes were capable of inducing interferon-gamma and interleukin-4. They successfully bound to their respective human leukocyte antigens alleles in in silico docking studies. The expected global population coverage of the T-cell epitopes and their restricted human leukocyte antigens alleles was 99.90%. The population coverage of endemic regions ranged from 99.99% (Papua New Guinea) to 21.81% (Liberia). Two vaccine constructs were generated using the Toll-like receptors 2 and 4 agonists, LprG and RpfE, respectively. Both constructs were antigenic, non-allergenic, non-toxic, thermostable, basic, and hydrophilic. The DNA sequences of the vaccine constructs underwent optimization and were successfully in-silico cloned with the pET-28a(+) plasmid. The vaccine constructs were successfully docked to their respective toll-like receptors. Molecular dynamics simulations were carried out to analyze the binding interactions within the complex. The generated binding energies indicate the stability of both complexes. The constructs generated in this study display severable favorable properties, with construct one displaying a greater range of favorable properties. However, further analysis and laboratory validation are required.

Design of a Multiepitope Vaccine against Chicken Anemia Virus Disease.

Chicken anemia virus (CAV) causes severe clinical and sub-clinical infection in poultry globally and thus leads to economic losses. The drawbacks of the commercially available vaccines against CAV disease signal the need for a novel, safe, and effective vaccine design. In this study, a multiepitope vaccine (MEV) consisting of T-cell and B-cell epitopes from CAV viral proteins (VP1 and VP2) was computationally constructed with the help of linkers and adjuvant. The 3D model of the MEV construct was refined and validated by different online bioinformatics tools. Molecular docking showed stable interaction of the MEV construct with TLR3, and this was confirmed by Molecular Dynamics Simulation. Codon optimization and in silico cloning of the vaccine in pET-28a (+) vector also showed its potential expression in the E. coli K12 system. The immune simulation also indicated the ability of this vaccine to induce an effective immune response against this virus. Although the vaccine in this study was computationally constructed and still requires further in vivo study to confirm its effectiveness, this study marks a very important step towards designing a potential vaccine against CAV disease.

An exploration of profile, perceptions, barriers, and predictors of research engagement among resident doctors: a report from CHARTING study.

Purpose/Aims: This research aimed to study the profile, perceptions, barriers, and predictors of Nigerian resident doctors' level of engagement in scientific research. Methods: This study was a descriptive cross-sectional quantitative survey of 438 resident doctors in Nigeria. This study forms a part of the big CHARTING Study, the protocol of which was published in "Nigeria Journal of Medicine 2019;28:198-205." Results: Three hundred and eighteen (72.8%) respondents were male and 119 (27.2%) were female. There were 229 (52.4%) registrars and 208 (47.6%) senior registrars, while residents in surgical versus nonsurgical specialties were 190 (44.5%) and 237 (55.5%), respectively. Three hundred and sixty-eight (85%) respondents had participated previously in research; 67 (15.6%) and 72 (16.6%) had their papers published in local or international journals, respectively; and only 46 (10.6%) had held first authorship positions in peer-reviewed journal publications. The significant barriers to research identified among them included lack of funding, lack of free time, inadequate training/knowledge on research methodology, and the onerous nature of clinical research. The independent predictor of previous engagement with research was years on current job (P = 0.007). This was similar to finding for the first authorship of a peer-reviewed article among the respondents (P = 0.017). Conclusion: This study concludes that publication and grantsmanship rates were very low among the surveyed resident doctors, despite their high rate of engagement in research projects. There is a need for increased research capacity building among resident doctors in Nigeria.

Molecular Interactions Associated with Coagulation of Organic Pollutants by 2S Albumin of Plant Proteins: A Computational Approach.

The removal of organic pollutants is a major challenge in wastewater treatment technologies. Coagulation by plant proteins is a promising technique for this purpose. The use of these proteins has been experimentally investigated and reported in the literature. However, the determination of the molecular interactions of these species is experimentally challenging and the computational approach offers a suitable alternative in gathering useful information for this system. The present study used a molecular dynamic simulation approach to predict the potentials of using Moringa oleifera (MO), Arachis hypogaea, Bertholletia excelsa, Brassica napus, and Helianthus annuus plant proteins for the coagulation of organic pollutants and the possible mechanisms of coagulation of these proteins. The results showed that the physicochemical and structural properties of the proteins are linked to their performance. Maximum coagulation of organic molecules to the proteins is between 50-100%. Among five proteins studied for coagulation, Brassica napus and Helianthus annuus performed better than the well-known MO protein. The amino acid residues interacting with the organic molecules play a significant role in the coagulation and this is peculiar with each plant protein. Hydrogen bond and π-interactions dominate throughout the protein-pollutants molecular interactions. The reusability of the proteins after coagulation derived from their structural quality analysis along with the complexes looks promising and most of them are better than that of the MO. The results showed that the seed proteins studied have good prediction potentials to be used for the coagulation of organic pollutants from the environment, as well as the insights into their molecular activities for bioremediation.

The search for a Buruli Ulcer vaccine and the effectiveness of the Bacillus Calmette-Guérin vaccine.

Buruli Ulcer is a neglected tropical disease that is caused by Mycobacterium ulcerans. It is not fatal; however, it manifests a range of devastating symptoms on the hosts' bodies. Various drugs and treatments are available for the disease; however, they are often costly and have adverse effects. There is still much uncertainty regarding the mode of transmission, vectors, and reservoir. At present, there are no official vector control methods, prevention methods, or a vaccine licensed to prevent infection. The Bacillus Calmette-Guérin vaccine developed against tuberculosis has some effectiveness against M. ulcerans. However, it is unable to induce long-lasting protection. Various types of vaccines have been developed based specifically against M. ulcerans; however, to date, none has entered clinical trials or has been released for public use. Additional awareness and funding are needed for research in this field and the development of more treatments, diagnostic tools, and vaccines.

Unravelling the drugability of MSI2 RNA recognition motif (RRM) protein and the prediction of their effective antileukemia inhibitors from traditional herb concoctions.

MSI2 is a homolog 2 of the Musashi RNA binding proteins (MSI) and is known to contribute to acute myeloid leukaemia (AML) and expressed up to 70% in AML patients. High expression of MSI2 has been found to lead to the lower overall survival of patients with AML. This study proposed the potential antagonists of MSI2 RNA-recognition motifs (MSI2 RRM1) derived from the LC-MS analysis of three traditional herbal samples. The LC-MS analysis of the three traditional herbs concoctions yields a total of 271 unique molecules of which 262 were screened against MSI2 RRM1 protein. After the dynamic study of the selected 8 top molecules from the virtual screening, the five most promising ligands emerged as potential MSI2 antagonists compare to the reference experimental molecule. The results show that the dynamic of MSI2 RRM1 protein is accompanied by a rare even of protein chain dissociation and re-association as evident in both the bound and unbound state of the protein. The unbound protein experience earlier chain dissociation compare to ligand-bound protein indicating that ligand binding to the protein slows down the dissociation time but thereafter increases the frequency of alternation between the protein chain association and dissociation after the first experience. Interestingly, the re-association of the protein chain is also accompanied by full restoration of the ligands to the binding site. The drug candidate Methotrexate (M3) and rescinnamine (M9) are listed among the promising antagonist of MSI2 with unique properties compared to a less promising molecule Ergotamine (M6).Communicated by Ramaswamy H. Sarma.

Maternal serum uric acid: a reliable prognostic indicator of foetal outcome among pre-eclamptic patients in a low resource setting.

BACKGROUND: Pre-eclampsia is a major cause of maternal and fetal morbidity and mortality in both developed and developing countries. Hyperuricemia is often associated with pre-eclampsia and when this occurs, fetal outcome may become worse. We evaluated the role of maternal serum uric acid as a prognostic indicator of fetal outcome in pre-eclamptic mothers. METHODS: A prospective case-control study in which 55 eligible pre-eclamptic patients at term were matched in maternal age and gestational age with 55 consecutive normotensive pregnant women. Venous blood samples were obtained and analyzed for serum uric acid. Following delivery, the fetal outcomes in the pre-eclamptic group and controls were determined. Data analysis was carried out using SPSS (version 21) and the level of statistical significance was set at p-value <.05. RESULTS: The mean serum uric acid levels of the pre-eclamptic subjects was significantly higher compared to their normotensive counterparts (12.7 ± 7.8 vs. 4.9 ± 1.2 mg/dL, p = .000). Babies with low birth weight, poor Apgar scores (at 1st and 5th minute of life) and those who required neonatal unit admission occurred more significantly among the pre-eclamptic women when compared with the controls (p = .000). However, the live birth rate of the case and control groups was comparable (94.5% vs. 100%, p = .079), Binary logistic regression analysis revealed a positive association between hyperuricemia and pre-eclampsia (OR = 18.8; 95% CI = 1.22-289.35, p = .035). Pre-eclamptic mothers with hyperuricemia had 4.41 odds of delivering babies with low birth weight when compared with pre-eclamptics without hyperuricemia (OR = 4.41; 95% CI = 0.76-25.5, p = .097); but Apgar scores and need for neonatal admission showed no association with maternal serum uric acid levels. CONCLUSION: This study therefore suggests that hyperuricemia is a strong prognostic indicator of LBW babies among women with pre-eclampsia.

Designing multiepitope-based vaccine against Eimeria from immune mapped protein 1 (IMP-1) antigen using immunoinformatic approach.

Drug resistance against coccidiosis has posed a significant threat to chicken welfare and productivity worldwide, putting daunting pressure on the poultry industry to reduce the use of chemoprophylactic drugs and live vaccines in poultry to treat intestinal diseases. Chicken coccidiosis, caused by an apicomplexan parasite of Eimeria spp., is a significant challenge worldwide. Due to the experience of economic loss in production and prevention of the disease, development of cost-effective vaccines or drugs that can stimulate defence against multiple Eimeria species is imperative to control coccidiosis. This study explored Eimeria immune mapped protein-1 (IMP-1) to develop a multiepitope-based vaccine against coccidiosis by identifying antigenic T-cell and B-cell epitope candidates through immunoinformatic techniques. This resulted in the design of 7 CD8+, 21 CD4+ T-cell epitopes and 6 B-cell epitopes, connected using AAY, GPGPG and KK linkers to form a vaccine construct. A Cholera Toxin B (CTB) adjuvant was attached to the N-terminal of the multiepitope construct to improve the immunogenicity of the vaccine. The designed vaccine was assessed for immunogenicity (8.59968), allergenicity and physiochemical parameters, which revealed the construct molecular weight of 73.25 kDa, theoretical pI of 8.23 and instability index of 33.40. Molecular docking simulation of vaccine with TLR-5 with binding affinity of - 151.893 kcal/mol revealed good structural interaction and stability of protein structure of vaccine construct. The designed vaccine predicts the induction of immunity and boosted host's immune system through production of antibodies and cytokines, vital in hindering surface entry of parasites into host. This is a very important step in vaccine development though further experimental study is still required to validate these results.

Immunoinformatics approach for multi-epitope vaccine design against P. falciparum malaria.

Plasmodium falciparum (P. falciparum) is a leading causative agent of malaria, an infectious disease that can be fatal. Unfortunately, control measures are becoming less effective over time. A vaccine is needed to effectively control malaria and lead towards the total elimination of the disease. There have been multiple attempts to develop a vaccine, but to date, none have been certified as appropriate for wide-scale use. In this study, an immunoinformatics method is presented to design a multi-epitope vaccine construct predicted to be effective against P. falciparum malaria. This was done through the prediction of 12 CD4+ T-cell, 10 CD8+ T-cell epitopes and, 1 B-cell epitope which were assessed for predicted high antigenicity, immunogenicity, and non-allergenicity through in silico methods. The Human Leukocyte Antigen (HLA) population coverage showed that the alleles associated with the epitopes accounted for 78.48% of the global population. The CD4+ and CD8+ T-cell epitopes were docked to HLA-DRB1*07:01 and HLA-A*32:01 successfully. Therefore, the epitopes were deemed to be suitable as components of a multi-epitope vaccine construct. Adjuvant RS09 was added to the construct to generate a stronger immune response, as confirmed by an immune system simulation. Finally, the structural stability of the predicted multi-epitope vaccine was assessed using molecular dynamics simulations. The results show a promising vaccine design that should be further synthesised and assessed for its efficacy in an experimental laboratory setting.

The design of multiepitope vaccines from plasmids of diarrheagenic Escherichia coli against diarrhoea infection: Immunoinformatics approach.

Diarrhoea infection is a major global health public problem and is caused by many organisms including diarrheagenic Escherichia coli pathotypes. The common problem with diarrhoea is the drug resistance of pathogenic bacteria, the most promising alternative means of preventing drug resistance is vaccination. However, there has not been any significant success in the prevention of diarrhoea caused by E. coli through vaccination. Epitope-based vaccine is gaining more attention due to its safety and specificity. Sequence variation of protective antigens of the pathogen has posed a new challenge in the development of epitope-based vaccines against the infection, leading to the necessity of multiepitope based design. In this study, immunoinformatics tools were used to design multiepitope vaccine candidates from plasmid genome sequences of multiple pathotypes of E. coli species involved in diarrhoea infections. The ability of the identified epitopes to be used as a cross-protect multiepitope vaccine was achieved by identifying conserved, immunogenic and antigenic peptides that can elicit CD4+ T-cell, CD8+ T-cell and B-cell and bind to MHC I and II HLA alleles. The molecular docking results of T-cell epitopes showed their well binding affinity to receptive protein and with a wider population coverage. The different multiepitope-based vaccines (MEVCs) candidates were constructed and based on the types of epitope linker they contained. The MEVCs exhibited very good binding interactions with the human immune receptor. Among multiepitope vaccines constructed, MEVC6, MEVCA and MEVCB are more promising as potential vaccine candidates for cross-protection against gastrointestinal infections according to the computational study. It is also hoped that after validation and testing, the predicted multiepitope-based vaccine candidates will probably resolve the challenge of immunological heterogeneity facing enteric vaccine development.

Immunoinformatics prediction of overlapping CD8+ T-cell, IFN-γ and IL-4 inducer CD4+ T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2).

At the beginning of the year 2020, the world was struck with a global pandemic virus referred to as SARS-CoV-2 (COVID-19) which has left hundreds of thousands of people dead. To control this virus, vaccine design becomes imperative. In this study, potential epitopes-based vaccine candidates were explored. Six hundred (600) genomes of SARS-CoV-2 were retrieved from the viPR database to generate CD8+ T-cell, CD4+ T-cell and linear B-cell epitopes which were screened for antigenicity, immunogenicity and non-allergenicity. The results of this study provide 19 promising candidate CD8+ T-cell epitopes that strongly overlap with 8 promising B-cells epitopes. Another 19 CD4+ T-cell epitopes were also identified that can induce IFN-γ and IL-4 cytokines. The most conserved MHC-I and MHC-II for both CD8+ and CD4+ T-cell epitopes are HLA-A*02:06 and HLA-DRB1*01:01 respectively. These epitopes also bound to Toll-like receptor 3 (TLR3). The population coverage of the conserved Major Histocompatibility Complex Human Leukocyte Antigen (HLA) for both CD8+ T-cell and CD4+ T-cell ranged from 65.6% to 100%. The detailed analysis of the potential epitope-based vaccine and their mapping to the complete COVID-19 genome reveals that they are predominantly found in the location of the surface (S) and membrane (M) glycoproteins suggesting the potential involvement of these structural proteins in the immunogenic response and antigenicity of the virus. Since the majority of the potential epitopes are located on M protein, the design of multi-epitope vaccine with the structural protein is highly promising though the whole M protein could also serve as a viable epitope for the development of an attenuated vaccine. Our findings provide a baseline for the experimental design of a suitable vaccine against SARS-CoV-2.

The conformational change of Plukenetia conophora oil derivatives and their acidic resistance, intra-fragment interactions, stability in different solvent media.

The synthesis of derivatives of bio-based lubricants from vegetable oil as an alternative to petroleum oil is significant due to the oil crisis, global warming, higher demand and serious environmental threat. In this study, the molecular properties of three derivatives of oil derived from Plukenetia conophora seeds, namely Plukenetia conophora oil (PK), rpoxidised Plukenetia conophora oil (EP) and poly(hydroxybutanethiol-ether) derivative of Plukenetia conophora oil (BP), were examined in acidic media and crystal form. The derivative BP has the highest resistance to acidic attack as evident from their poor interaction with acidic H3O+ from both HCl and HNO3. BP also has the best tendency of forming a crystal as evident from the lowest atomic diffusion in crystal model (L12). However, the result of the molecular electrostatic potential (MESP) analysis shows that BP has more electron-deficient surface compare to EP derivatives. The derivative BP is also found to have the lowest potential energy and higher root means square deviation (RMSD) of its atoms. Density clustering analysis further confirms that BP did not retain its most stable conformation for a longer period of simulation compared to PK and EP. The most visited conformation from the hierarchical and density clustering also corresponds to the minimum potential energy on the potential energy surface.Graphical abstract.

Properties of Alkaline-Earth-Metal Polynitrogen Ternary Materials at High Pressure.

We report the formation of cubic and tetragonal BaSrN3 at 100 GPa using an ab initio structure search method. Pressure ramping to 0 GPa reveals a reaction pressure threshold of 4.92 and 7.23 GPa for the cubic and tetragonal BaSrN3, respectively. The cubic phase is stabilized by coulombic interaction between the ions. Meanwhile, tetragonal BaSrN3 is stabilized through an expansion of the d-orbital in Ba and Sr atoms that is compensated by delocalization of π-electrons in N through reduction of π overlap. Elastic properties analysis suggests that both phases are mechanically stable. The structures also have high melting points as predicted using an empirical model, and all imaginary modes vanishes at about 2000 K. These results have significant implication for the design of cleaner and environmentally friendly high energy density materials.