Cracking the Code: Enhancing Molecular Tools for Progress in Nanobiotechnology.

Nature continually refines its processes for optimal efficiency, especially within biological systems. This article explores the collaborative efforts of researchers worldwide, aiming to mimic nature's efficiency by developing smarter and more effective nanoscale technologies and biomaterials. Recent advancements highlight progress and prospects in leveraging engineered nucleic acids and proteins for specific tasks, drawing inspiration from natural functions. The focus is developing improved methods for characterizing, understanding, and reprogramming these materials to perform user-defined functions, including personalized therapeutics, targeted drug delivery approaches, engineered scaffolds, and reconfigurable nanodevices. Contributions from academia, government agencies, biotech, and medical settings offer diverse perspectives, promising a comprehensive approach to broad nanobiotechnology objectives. Encompassing topics from mRNA vaccine design to programmable protein-based nanocomputing agents, this work provides insightful perspectives on the trajectory of nanobiotechnology toward a future of enhanced biomimicry and technological innovation.

Immunostimulation of Fibrous Nucleic Acid Nanoparticles Can be Modulated through Aptamer-Based Functional Moieties: Unveiling the Structure-Activity Relationship and Mechanistic Insights.

Fibrous nanomaterials containing silica, titanium oxide, and carbon nanotubes are notoriously known for their undesirable inflammatory responses and associated toxicities that have been extensively studied in the environmental and occupational toxicology fields. Biopersistance and inflammation of "hard" nanofibers prevent their broader biomedical applications. To utilize the structural benefits of fibrous nanomaterials for functionalization with moieties of therapeutic significance while preventing undesirable immune responses, researchers employ natural biopolymers─RNA and DNA─to design "soft" and biodegradable nanomaterials with controlled immunorecognition. Nucleic acid nanofibers have been shown to be safe and efficacious in applications that do not require their delivery into the cells such as the regulation of blood coagulation. Previous studies demonstrated that unlike traditional therapeutic nucleic acids (e.g., CpG DNA oligonucleotides) nucleic acid nanoparticles (NANPs), when used without a carrier, are not internalized by the immune cells and, as such, do not induce undesirable cytokine responses. In contrast, intracellular delivery of NANPs results in cytokine responses that are dependent on the physicochemical properties of these nanomaterials. However, the structure-activity relationship of innate immune responses to intracellularly delivered fibrous NANPs is poorly understood. Herein, we employ the intracellular delivery of model RNA/DNA nanofibers functionalized with G-quadruplex-based DNA aptamers to investigate how their structural properties influence cytokine responses. We demonstrate that nanofibers' scaffolds delivered to the immune cells using lipofectamine induce interferon response via the cGAS-STING signaling pathway activation and that DNA aptamers incorporation shields the fibers from recognition by cGAS and results in a lower interferon response. This structure-activity relationship study expands the current knowledge base to inform future practical applications of intracellularly delivered NANPs as vaccine adjuvants and immunotherapies.

Characterization of PAMAM Dendrimers for the Delivery of Nucleic Acid Nanoparticles.

The protocols described in this book chapter are meant to be used as an outline and guideline to explore the use of a cationic, polymeric, and synthetic carrier-poly (amidoamine) (PAMAM) dendrimers. The amine-terminated, hyperbranched structures have been identified as a vehicle for the delivery of nucleic acids. As such, clear protocols for the optimization of dendrimer usage should be set in place. This chapter details the experiments used to determine the ratio that dendrimers and nucleic acids should be complexed at through the use of binding assays, nuclease protection assays, and competitive binding assays.

Dynamic Nanostructures for Conditional Activation and Deactivation of Biological Pathways.

Nucleic acid nanotechnology utilizes natural and synthetic structural motifs to build versatile nucleic acid nanoparticles (NANPs). These rationally designed assemblies can be further equipped with functional nucleic acids and other molecules such as peptides, fluorescent dyes, etc. In addition to nucleic acids that directly interact with the regulated target gene transcripts, NANPs can display decoys, wherein the oligonucleotide stretches with transcription factor binding sequences, preventing transcription initiation. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a group of five crucial transcription factors regulating the pathogenesis of inflammatory diseases and cancer; as such, they are relevant targets for therapy. One therapeutic approach involves interdependent self-recognizing hybridized DNA/RNA fibers designed to bind NF-κB and prevent its interaction with the promotor region of NF-κB-dependent genes involved in inflammatory responses. Decoying NF-κB results in the inability to initiate transcription of regulated genes, showing a promising approach to gene regulation and gene therapy. The protocol described herein provides detailed steps for the synthesis of NF-κB decoy fibers, as well as their characterization using polyacrylamide gel electrophoresis (to confirm desired physicochemical properties and purity) and functional bioassays (to confirm desired biological activity).

Bacterial immunotherapy is highly effective in reducing recurrent upper respiratory tract infections in children: a prospective observational study.

PURPOSE: Whilst immunotherapy is an appealing option as it could reduce the burden of recurrent pediatric respiratory tract infections (RTI), there is limited evidence on its effectiveness and more research was requested in order to better understand this therapeutic modality. METHODS: We performed a prospective cohort study involving 57 subjects to assess the safety and effectiveness a 3-month regimen of either typified or patient-specific bacterial lysates could have in reducing the number of RTIs in children aged 0 to 11 years with histories of recurrent episodes. RESULTS: After a 6-month follow-up, the number of RTIs and school absenteeism dropped sharply and significantly, from an adjusted mean (standard error) of 0.6 (0.04) episodes/month to 0.1 (0.03) episodes/month (74.7% reduction, P < 0.001), and from an adjusted mean score of 4.6 (1.06) points to 0.0 (0.01) points over 10 (99.5% reduction, P < 0.001), respectively. There was also a significant decrease in the severity of symptoms. No adverse reactions were observed. CONCLUSION: The use of the study product is associated with a decreased risk of recurrent RTIs in children, with a very favorable safety profile that warrants further investigation in randomized clinical trials.

Patient adherence with infection control measures on a novel 'COVID-19 triage' psychiatric in-patient ward.

BACKGROUND: Intra-hospital transmission of coronavirus disease 2019 (COVID-19) is a major concern. Psychiatric in-patient units pose unique challenges for the prevention of transmission. 'COVID-triage' wards with strict infection control procedures have been implemented to prevent the spread of infection, but little is known about the extent to which psychiatric in-patients adhere to these procedures. AIMS: To examine patient adherence with infection control measures on a novel 'COVID-triage' psychiatric in-patient ward in London, England. METHOD: This was an observational study of adherence with infection control measures. The proportion of patients who were adherent with infection control measures was calculated. The association of adherence with demographic and clinical factors was examined. RESULTS: The majority of patients (n = 138/176, 78.4%) were not adherent with infection control measures. However, adherence did improve when patients who were non-adherent were given direct instructions by staff during clinical contact. Patients with diagnoses of psychotic disorders, personality disorders and substance use disorders were less likely to be adherent than those without these diagnoses. CONCLUSIONS: Psychiatric in-patients show poor adherence with infection control measures. Proactive engagement by staff is key to improving patients' adherence. Urgent efforts are needed to identify and implement other effective methods of improving adherence in acute settings.

Prácticas de lectura y escritura académicas en un programa de fonoaudiología / Reading and Writing Academic Practices in a Language and Speech Pathology Syllabus

La mayoría de trabajos de investigación que se han desarrollado sobre el tema en Latinoamérica, atribuyen a los mismos estudiantes sus problemas de lectura y escritura, considerando factores de tipo cognitivo o sociocultural, de modo que son escasos los trabajos que intentan comprender este fenómeno desde lo que sucede en las aulas de clase universitarias. En este artículo se presen-tan algunos resultados de una investigación cuyo objetivo fue caracterizar las prácticas de lectura y escritura académicas en cuatro asignaturas profesionales del programa de Fonoaudiología de una universidad pública colombiana. Este estudio cualitativo se realizó a través de observacio-nes directas y registros en video de clases, entrevistas a docentes y análisis de los programas de asignaturas seleccionadas. Se encontró que las docentes promueven diversas prácticas de lectura y escritura con propósitos como apoyar el aprendizaje y realizar la evaluación tanto de los conte-nidos profesionales, como de los procesos lectores y escritores. También se evidenció que ofrecen a sus estudiantes algunos apoyos para las tareas de lectura y escritura que asignan, aunque lo que proponen en los programas de asignatura y lo que refieren durante las entrevistas, refleja que no necesariamente las profesoras ayudan a sus pupilos de manera intencional. La reflexión sobre los resultados arrojados por este trabajo podría permitir a los programas académicos de Fonoaudio-logía, y al gremio en general, redimensionar la relación entre aprendizaje, lectura y escritura en el ámbito universitario.

The most of research papers, developed about this topic in Latin America, have been attributed to students, their reading and writing problems that are considered socio cultural factors and cognitive, factors this way the research works which have tried to understand this phenomenon since what happens in University classes. In this article some investigation results are presented, whose main aim was to characterize reading and writing practices in four professional subjects of language and speech pathology syllabus in a public university. This qualitative study was carried out through direct observation, video films in classes,interviews with the teachers and selected subject syllabuses. Among the results, it has been found that the teachers promote several rea-ding and writing practices with different purposes, such as helping the learning and making eva-luation as professional contents as reading and writing process. Also, it shows that teachers give to their students some supports for developing Reading and writing tasks assigned, although there is a gap between their purposes in signature program and their answers in the interview, it reflects that teachers do not necessarily help their students intentionally.The reflection about this investigation resultas would permit to the academic programs of language and speech pathology, and the group in general to resize the relationship among learning, reading and writing in the university field.