Structure-Based Stabilization of SOSIP Env Enhances Recombinant Ectodomain Durability and Yield.

The envelope glycoprotein (Env) is the main focus of human immunodeficiency virus type 1 (HIV-1) vaccine development due to its critical role in viral entry. Despite advances in protein engineering, many Env proteins remain recalcitrant to recombinant expression due to their inherent metastability, making biochemical and immunological experiments impractical or impossible. Here, we report a novel proline stabilization strategy to facilitate the production of prefusion Env trimers. This approach, termed "2P," works synergistically with previously described SOSIP mutations and dramatically increases the yield of recombinantly expressed Env ectodomains without altering the antigenic or conformational properties of near-native Env. We determined that the 2P mutations function by enhancing the durability of the prefusion conformation and that this stabilization strategy is broadly applicable to evolutionarily and antigenically diverse Env constructs. These findings provide a new Env stabilization platform to facilitate biochemical research and expand the number of Env variants that can be developed as future HIV-1 vaccine candidates. IMPORTANCE Recent estimates have placed the number of new human immunodeficiency virus type 1 (HIV-1) infections at approximately 1.5 million per year, emphasizing the ongoing and urgent need for an effective vaccine. The envelope (Env) glycoprotein is the main focus of HIV-1 vaccine development, but, due to its inherent metastability, many Env variants are difficult to recombinantly express in the relatively large quantities that are required for biochemical studies and animal trials. Here, we describe a novel structure-based stabilization strategy that works synergistically with previously described SOSIP mutations to increase the yield of prefusion HIV-1 Env.

Effectiveness of alternative approaches to integrating SDOH into medical education: a scoping review.

BACKGROUND: There is increasing recognition of including social determinants of health (SDOH) in teaching for future doctors. However, the educational methods and the extent of integration into the curriculum vary considerably-this scoping review is aimed at how SDOH has been introduced into medical schools' curricula. METHODS: A systematic search was performed of six electronic databases, including PubMed, Education Source, Scopus, OVID (Medline), APA Psych Info, and ERIC. Articles were excluded if they did not cover the SDOH curriculum for medical students; were based on service-learning rather than didactic content; were pilot courses, or were not in English, leaving eight articles in the final study. RESULTS: The initial search yielded 654 articles after removing duplicates. In the first screening step, 588 articles were excluded after applying inclusion and exclusion criteria and quality assessment; we examined 66 articles, a total of eight included in the study. There was considerable heterogeneity in the content, structure and duration of SDOH curricula. Of the eight included studies, six were in the United States(U.S.), one in the United Kingdom (U.K.) and one in Israel. Four main conceptual frameworks were invoked: the U.S. Healthy People 2020, two World Health Organisation frameworks (The Life Course and the Michael Marmot's Social Determinants of Health), and the National Academic of Science, Engineering, and Medicine's (Framework For educating Health Professionals to Address the Social Determinants of Health). In general, programs that lasted longer appeared to perform better than shorter-duration programmes. Students favoured interactive, experiential-learning teaching methods over the traditional classroom-based teaching methods. CONCLUSION: The incorporation of well-structured SDOH curricula capturing both local specification and a global framework, combined with a combination of traditional and interactive teaching methods over extended periods, may be helpful in steps for creating lifelong learners and socially accountable medical school education.

Clinical Analysis and Applications of mRNA Vaccines in Infectious Diseases and Cancer Treatment.

Vaccination, for centuries, has been a potent preventive technique to treat morbidities. The messenger RNA (mRNA) vaccine technology is an innovative biomedical approach utilized in developing antigen-specific vaccines that can generate adaptive immune responses, triggering both humoral and cellular immunity to enhance the body's defense against specific infections. This review provides a comprehensive, comparative analysis of mRNA vaccine technology and conventional vaccines by focusing on the structures, components, and classifications. An exploratory analysis of the similarities and differences between mRNA vaccine technology and live-attenuated vaccines highlights the mechanisms by which mRNA vaccines elicit immune responses. This review extensively discusses the production, stability, synthesis, and delivery processes associated with mRNA vaccines, showcasing the advancements and technological superiority of this approach over conventional vaccine technologies. Additionally, the potential of mRNA vaccine technology as a potent alternative for the development of vaccine candidates targeting HIV and cancer is examined.

Corrigendum to "A detailed review on the phytochemical profiles and antidiabetic mechamisms of momordica charantia" [Heliyon 8 4 April 2022 Article e09253].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e09253.].

A detailed review on the phytochemical profiles and anti-diabetic mechanisms of Momordica charantia.

Diabetes mellitus is the most well-known endocrine dilemma suffered by hundreds of million people globally, with an annual mortality of more than one million people. This high mortality rate highlights the need for in-depth study of anti-diabetic agents. This review explores the phytochemical contents and anti-diabetic mechanisms of M. charantia (cucurbitaceae). Studies show that M. charantia contains several phytochemicals that have hypoglycemic effects, thus, the plant may be effective in the treatment/management of diabetes mellitus. Also, the biochemical and physiological basis of M. charantia anti-diabetic actions is explained. M. charantia exhibits its anti-diabetic effects via the suppression of MAPKs and NF-κßin pancreatic cells, promoting glucose and fatty acids catabolism, stimulating fatty acids absorption, inducing insulin production, ameliorating insulin resistance, activating AMPK pathway, and inhibiting glucose metabolism enzymes (fructose-1,6-bisphosphate and glucose-6-phosphatase). Reviewed literature was obtained from credible sources such as PubMed, Scopus, and Web of Science.