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Rotavirus (RV) is a common double-stranded RNA virus that causes diarrheal disease in young children. The prevalent species, Rotavirus A (RVA), is responsible for over 90% of human RV infections. With significant morbidity and mortality, this pathogen poses a serious global health challenge, particularly in underdeveloped countries. This study presents an immunoinformatics approach for designing an mRNA vaccine based on a multi-peptide construct to elicit robust immune responses against RVA. The VP4 was analyzed from 40 sequences using phylogenetic analysis. Prediction of cytotoxic (CTL) and helper T cell (HTL) epitopes was performed and validated. The 17 high-conservancy CTL/HTL epitopes were selected for vaccine construction. The mRNA vaccine based on multi-peptide was engineered with human beta-defensin 3 (hBD3) adjuvant and linkers to enhance immunogenicity. The designed mRNA vaccine product exhibited favorable physicochemical properties and was predicted to be a probable antigen, non-allergenic, and non-toxic. 2D and 3D structure validation demonstrated the quality of the model. Molecular docking with Toll-like receptor 2/3 (TLR2/3) indicated favorable interaction, and peptide docking with MHC-I/II alleles showed strong binding affinities and have significant Residue-Residue interactions. Simulation of immune responses revealed potent B-cell and T-cell activities, macrophage responses, and significant cytokine synthesis. Molecular dynamics simulation (MDS) confirmed the structural stability of the TLR3-vaccine complex, and MHC-peptide in 200ns and STQFTDFVSLNSLRF peptide have shown good interaction with MHC molecule. In addition, the MM/GBSA analysis yielded a binding free energy of − 89.77 kcal/mol, indicating a strong and stable interaction between the vaccine construct and the target receptor. Codon optimization and mRNA secondary structure prediction were carried out for efficient translation. Additionally, population coverage analysis indicated the vaccine’s effectiveness worldwide with 100% value. Overall, this study showcases a promising immunoinformatics approach for designing an mRNA vaccine based on a multi-peptide construct targeting RVA. The findings support the potential of this vaccine design to elicit robust and widespread immune responses against RVA infection, paving the way for future vaccine development strategies and this study needs experimental validation.

Background Streptococcus pneumoniae (Pneumococcus) has remained a leading cause of fatal infections such as pneumonia, meningitis, and sepsis. Moreover, this pathogen plays a major role in bacterial co-infection in patients with life-threatening respiratory virus diseases such as influenza and COVID-19. High morbidity and mortality in over one million cases, especially in very young children and the elderly, are the main motivations for pneumococcal vaccine development. Due to the limitations of the currently marketed polysaccharide-based vaccines, non-serotype-specific protein-based vaccines have received wide research interest in recent years. One step further is to identify high antigenic regions within multiple highly-conserved proteins in order to develop peptide vaccines that can affect various stages of pneumococcal infection, providing broader serotype coverage and more effective protection. In this study, immunoinformatics tools were used to design an effective multi-epitope vaccine in order to elicit neutralizing antibodies against multiple strains of pneumococcus. Results The B- and T-cell epitopes from highly protective antigens PspA (clades 1–5) and PhtD were predicted and immunodominant peptides were linked to each other with proper linkers. The domain 4 of Ply, as a potential TLR4 agonist adjuvant candidate, was attached to the end of the construct to enhance the immunogenicity of the epitope vaccine. The evaluation of the physicochemical and immunological properties showed that the final construct was stable, soluble, antigenic, and non-allergenic. Furthermore, the protein was found to be acidic and hydrophilic in nature. The protein 3D-structure was built and refined, and the Ramachandran plot, ProSA–web, ERRAT, and Verify3D validated the quality of the final model. Molecular docking analysis showed that the designed construct via Ply domain 4 had a strong interaction with TLR4. The structural stability of the docked complex was confirmed by molecular dynamics. Finally, codon optimization was performed for gene expression in E. coli , followed by in silico cloning in the pET28a(+) vector. Conclusion The computational analysis of the construct showed acceptable results, however, the suggested vaccine needs to be experimentally verified in laboratory to ensure its safety and immunogenicity.

Streptococcus pneumoniae (pneumococcus) is a major cause of pneumonia, meningitis, bacteremia, and secondary infections following viral respiratory diseases such as influenza and COVID-19. Because current polysaccharide-based vaccines protect only against selected serotypes, there is a pressing need for serotype-independent strategies. In this study, a novel multi-epitope mRNA vaccine candidate against S. pneumoniae was designed using immunoinformatics approaches. The immunodominant regions of PsaA and PspA were fused with flexible linkers, and TLR agonist domains derived from Ply and PepO were incorporated as adjuvants to enhance immune activation. The resulting construct, named YAPO, was predicted to possess favorable physicochemical and immunological properties, including stability, solubility, antigenicity, non-allergenicity, and non-toxicity. Additional analyses—including IFN-γ epitope prediction, conformational B-cell epitope mapping, HLA docking, vaccine–TLR docking, molecular dynamics, and immune simulations— indicated potential to induce robust immune responses. The mRNA sequence was engineered with essential regulatory elements (5′ cap, UTRs, Kozak sequence, signal peptide, and poly(A) tail) to promote efficient expression, and codon optimization suggested compatibility with mammalian translation. In silico cloning into the pcDNA3.1(+) vector further supported potential construct feasibility. Overall, these findings highlight that YAPO-mRNA is a promising serotype-independent pneumococcal vaccine candidate that merits further experimental validation.

Background Streptococcus pneumoniae is the leading reason for invasive diseases including pneumonia and meningitis, and also secondary infections following viral respiratory diseases such as flu and COVID-19. Currently, serotype-dependent vaccines, which have several insufficiency and limitations, are the only way to prevent pneumococcal infections. Hence, it is plain to need an alternative effective strategy for prevention of this organism. Protein-based vaccine involving conserved pneumococcal protein antigens with different roles in virulence could provide an eligible alternative to existing vaccines. Methods In this study, PspC, PhtD and PsaA antigens from pneumococcus were taken to account to predict B-cell and helper T-cell epitopes, and epitope-rich regions were chosen to build the construct. To enhance the immunogenicity of the epitope-based vaccine, a truncated N-terminal fragment of pneumococcal endopeptidase O (PepO) was used as a potential TLR2/4 agonist which was identified by molecular docking studies. The ultimate construct was consisted of the chosen epitope-rich regions, along with the adjuvant role (truncated N-PepO) and suitable linkers. Results The epitope-based vaccine was assessed as regards physicochemical properties, allergenicity, antigenicity, and toxicity. The 3D structure of the engineered construct was modeled, refined, and validated. Molecular docking and simulation of molecular dynamics (MD) indicated the proper and stable interactions between the vaccine and TLR2/4 throughout the simulation periods. Conclusions For the first time this work presents a novel vaccine consisting of epitopes of PspC, PhtD, and PsaA antigens which is adjuvanted with a new truncated domain of PepO. The computational outcomes revealed that the suggested vaccine could be deemed an efficient therapeutic vaccine for S. pneumoniae ; nevertheless , in vitro and in vivo examinations should be performed to prove the potency of the candidate vaccine.

Background Persistent infection with high-risk Human papillomavirus (HPV), specifically HPV-16, is the leading cause of cervical cancer. Although preventative vaccines have shown significant efficacy in preventing HPV infection, cervical cancer is a significant public health issue that affects millions of women worldwide. Modern therapeutic approaches, such as peptide vaccines, could be promising and have potential for the treatment of the HPV-infected population. Methods A HPV16-E7 multi-epitopic vaccine (MEVE7) was designed to comprise potent CD4 + and CD8 + T cell epitopes and optimally expressed in a prokaryotic expression system. Polyclonal antibodies were generated, and their reactivity with immunizing antigen and native protein in E7 expressing cells (TC-1) was assessed by ELISA and immunofluorescent staining, respectively. The efficacy of the vaccine was assessed in a therapeutic animal model of HPV-induced cancer. Results Our study revealed that the final construct was successfully expressed in E. coli BL21 (DE3)-gold within 4 h of induction as inclusion bodies. Among the tested solubilization buffers, the buffer with a pH of 12 and containing 2 M urea showed the highest solubilization effect. Polyclonal antibodies directed against the E7 multi-epitope vaccine were able to react strongly with the immunizing antigen and E7-bearing cells (TC-1). Immunization of TC-1 tumor-bearing mice with HPV16-E7, markedly delayed tumor growth and propagation. Conclusion The poly-epitope vaccine for HPV16-E7, as expressed and purified in this research, is highly immunogenic and capable of triggering E7-specific antibodies, making it a potential therapeutic HPV vaccine. Further research is needed to optimize the vaccination schedule and assess the E7-specific immune cell profile.

THE RAPID INCREASE IN URBAN POPULATIONS HAS HEIGHTENED THE NEED FOR EFFICIENT RESOURCE MANAGEMENT, MAKING THE CONCEPT OF SMART CITIES ESSENTIAL FOR SUSTAINABLE URBAN DEVELOPMENT. SMART CITIES LEVERAGE INFORMATION AND COMMUNICATION TECHNOLOGY (ICT) TO ENHANCE URBAN FUNCTIONS, INCREASE THE QUALITY OF LIFE, AND PROMOTE ENVIRONMENTAL SUSTAINABILITY. THROUGH ADVANCED SENSORS, INTERNET OF THINGS (IOT) DEVICES, AND DATA ANALYTICS, SMART CITIES GATHER REAL-TIME INFORMATION TO SUPPORT DECISION-MAKING BY MUNICIPALITIES, BUSINESSES, AND CITIZENS. KEY COMPONENTS INCLUDE SMART ENVIRONMENT, SMART TRANSPORTATION, DIGITAL ECONOMY, SMART GOVERNANCE, AND SMART LIVING. THIS PAPER EXPLORES VARIOUS DEFINITIONS OF A SMART CITY AND EXAMINES THE ROLE OF CUTTING-EDGE TECHNOLOGIES SUCH AS 5G, SMART ENERGY SYSTEMS, WASTE MANAGEMENT, AND BUILDING MANAGEMENT SYSTEMS IN IMPROVING INFRASTRUCTURE AND URBAN SUSTAINABILITY. BY ENABLING DATADRIVEN APPROACHES TO INFRASTRUCTURE, SECURITY, AND SUSTAINABILITY, THESE TECHNOLOGIES CONTRIBUTE SIGNIFICANTLY TO ADDRESSING URBAN CHALLENGES. ADDITIONALLY, THIS PAPER IDENTIFIES ESSENTIAL SUCCESS FACTORS, SUCH AS HOLISTIC DEVELOPMENT STRATEGIES, CITIZEN-CENTRIC DESIGN, GOVERNMENT SUPPORT, AND A FOCUS ON ENVIRONMENTAL SUSTAINABILITY, WHICH DRIVE THE EFFECTIVE IMPLEMENTATION OF SMART CITY PROJECTS. AS CITIES EVOLVE, THESE INNOVATIONS PRESENT OPPORTUNITIES TO OPTIMIZE RESOURCES, REDUCE COSTS, AND CREATE MORE RESILIENT, EFFICIENT, AND LIVEABLE URBAN ENVIRONMENTS.

Purpose: Among all known human coronaviruses, some viruses (e.g., SARS-CoV-2) cause severe pneumonia or even death. With the regard to its spread and the importance of its rapid identification/treatment, and because pAbs are relatively cheap, able to bind to more sites on antigens and even neutralize them, this study was done for the production and purification of anti-SARS-CoV-2 polyclonal antibodies (pAb) in rats. Methods: Viral antigen purification was performed by PEG/NaCl precipitation. The efficiency of the sucrose cushion method was also investigated to produce a purer antigen. Immunization was done and antibody purification was performed by ammonium sulfate precipitation (33%), dialysis, and ion-exchange chromatography. Western blotting and enzyme-linked immunosorbent assay (ELISA) were performed to verify the antibody specificity. All data were analyzed by SPSS software. Results: The results showed that the amount of concentrated virus increased with the increase of PEG concentration. Moreover, the sucrose cushion method increased its purity. Besides, induction of immune response in rats for pAb production with high titers was reached via these antigens and ELISA/western blot results indicated a suitable antibody-antigen interaction. Additionally, it was shown that ion-exchange chromatography could be a suitable technique for IgG purification. Conclusion: Herein, we presented a simple and cheap method for the purification of whole viral particles with relatively high quality. The results verified that these antigens could elicit a good immune response in the rat. The obtained pAbs showed a good specificity toward SARS-CoV-2 antigens. Accordingly, this study proposes a promising method for viral vaccine development.

Nowadays, empowerment is considered as one of the useful tools for improving the quality of employees and increasing the effectiveness of the organization. In order to achieve this, organizations, by empowering the relevant employees in order to encourage them to take action without pressure, respect the collective interests of the organization with the least supervision and perform their duties as owners of the organization. They are deprived of face to face citizenship behavior (trans-role and sub-role) is part of the operational characteristics of the company. Physiological needs (self-efficacy, competence, communication) are a set of personal and social characteristics and feelings and thoughts related to them, which one acquires through the ability to interact with oneself and by finding ideas that affect citizenship behavior. And affect employee empowerment. This research is descriptive-survey and correlational. Due to the researcher's lack of access to municipal staff in Qom province, Morgan table sampling method was used. Validity and reliability of questions with Cronbach's alpha above 0.7. Research data were collected using a standard questionnaire and analyzed. The pls structural equation model is used. The result of the hypothesis test indicates the positive effect of physiological needs on employee empowerment and citizenship behavior, and also citizenship behavior affects the relationship between physiological needs and employee empowerment.

Every year, a major part of the country's national income is spent on investment in construction projects in which construction has a significant share. The performance of the construction project relies on various aspects of project management. Since effective project management begins with the integration of processes and performance management performance in the construction organization, integrated management is of great importance. The purpose of this study is to investigate the effect of different components of integration management on the performance of construction project management and to examine the relationship between those components and the integration of management integration on the empowerment of managers. Proposed components of integration management are the development of a knowledge integration, staff integration, supply chain integration on the dimensions of project management performance management, which are quality, safety, and customer satisfaction are effective. Among these people, 203 project experts were selected based on Morgan table method in proportion to the volume. Through the research tool, the questionnaire was studied to measure the validity and reliability of the variables, the content of the structure was examined and approved, and LISREL-SPSS software was used to analyze the confirmatory and inferential factor analysis information. Indicates that employee integration management has an effect on the empowerment of managers with a coefficient of 0.560, evaluation management 0.891 and executive 0.614 and also integration management has a positive effect on organizational performance management of 0.756. This means changing the process of project performance management in construction companies.

Introduction: Cervical cancer is the leading cause of morbidity and cancer mortality in women throughout the world and persistent infection with human papillomavirus (HPV) is the main etiology for the development of this cancer. Peptide vaccines derived from E6 and E7 oncogenes are promising candidates for HPV vaccine production due to their safety, high stability, and ease of production. In the current study, expression strains such as Escherichia coli BL21 (DE3), BL21 (DE3)-AI, Rosetta, C41 (DE3), and BL21 (DE3)-pLysS were applied for poly epitopic E6 expression and the effects of temperature, induction time, and inducer concentration on the expression level of recombinant HPV16-E6 polypeptide protein were examined in the mentioned strains. Materials and Methods: In the present study, the optimized gene of E6 recombinant protein was cloned into pET28a vector under the control of T7 promoter and the resulting plasmid was successfully transformed into Escherichia coli strains BL21 (DE3), BL21 (DE3)-AI, Rosetta, C41 (DE3), and BL21 (DE3)-pLysS. Then, the ability of these strains to express the desired recombinant protein in different conditions was compared. Two temperatures of 25 ° C and 37 ° C, IPTG concentrations between 0.1 and 1.0 mM, and different incubation times were selected to examine the expression level of recombinant E6 protein in these strains. Results: The highest level of expression was obtained in Escherichia coli BL21 (DE3) -AI strain inducing at Optical Density (OD) of 0.9, 0.1 mM IPTG, and 16 hours induction at 25 °C. Discussion and Conclusion: The results of this study can be used to produce E6 protein as a vaccine candidate in the treatment of HPV-related cancers.