Emerging Progress of RNA-Based Antitumor Therapeutics.

RNA-based therapeutics (e.g., mRNAs, siRNAs, microRNAs, ASOs, and saRNAs) have considerable potential for tumor treatment. The development and optimization of RNA modifications and delivery systems enable the stable and efficient delivery of RNA cargos in vivo to elicit an antitumor response. Targeted RNA-based therapeutics with multiple specificities and high efficacies are now available. In this review, we discuss progress in RNA-based antitumor therapeutics, including mRNAs, siRNAs, miRNAs, ASOs, saRNAs, RNA aptamers, and CRISPR-based gene editing. We focus on the immunogenicity, stability, translation efficiency, and delivery of RNA drugs, and summarize their optimization and the development of delivery systems. In addition, we describe the mechanisms by which RNA-based therapeutics induce antitumor responses. Furthermore, we review the merits and limitations of RNA cargos and their therapeutic potential for cancers.

Trans-splicing facilitated by RNA pairing greatly expands sDscam isoform diversity but not homophilic binding specificity.

The Down syndrome cell adhesion molecule 1 (Dscam1) gene can generate tens of thousands of isoforms via alternative splicing, which is essential for nervous and immune functions. Chelicerates generate approximately 50 to 100 shortened Dscam (sDscam) isoforms by alternative promoters, similar to mammalian protocadherins. Here, we reveal that trans-splicing markedly increases the repository of sDscamß isoforms in Tetranychus urticae. Unexpectedly, every variable exon cassette engages in trans-splicing with constant exons from another cluster. Moreover, we provide evidence that competing RNA pairing not only governs alternative cis-splicing but also facilitates trans-splicing. Trans-spliced sDscam isoforms mediate cell adhesion ability but exhibit the same homophilic binding specificity as their cis-spliced counterparts. Thus, we reveal a single sDscam locus that generates diverse adhesion molecules through cis- and trans-splicing coupled with alternative promoters. These findings expand understanding of the mechanism underlying molecular diversity and have implications for the molecular control of neuronal and/or immune specificity.

Privacy and Well-Being in Aged Care Facilities with a Crowded Living Environment: Case Study of Hong Kong Care and Attention Homes.

This study aims to understand the relationship between bedroom privacy and well-being of the elderly in aged care facilities with a compact living situation. A majority of studies on this topic were carried out in a low-density population context. The crowded living situation might compromise the well-being of residents. This study proposed five architectural parameters to measure bedroom privacy in aged care facilities: total open surface per unit, openness/solid ratio per bed, height of partition wall, number of people per unit, and personal control over bedroom privacy. SF-12 v.2 Health Survey was used to collect information on physical and mental health status. The study surveyed nine Care & Attention homes and their 213 residents in Hong Kong. The total open surface per unit and the openness/solid ratio per bed were positively associated with the physical health of residents. The height of partition walls was associated negatively with their physical and mental health conditions, and the number of people per unit was negatively associated with their physical health. More than half of respondents preferred a single unit with high partition walls; however, 40% of respondents preferred low partition walls. The provision of privacy for the elderly should be balanced with their needs for social interactions; total open surface per unit, openness/solid ratio per bed and height of partition wall should be taken into consideration. The study provides evidence and design guidelines for improving privacy in aged care facilities with a compact living environment.

Legibility of floor plans and wayfinding satisfaction of residents in Care and Attention homes in Hong Kong.

OBJECTIVE: Focusing on Hong Kong Care and Attention homes which provide residential care, meals, personal care and limited nursing care for older people, this study aimed to understand the impact of floor plans' legibility (layout and complexity) on residents' wayfinding satisfaction and self-reported health status. METHODS: A questionnaire survey was conducted in nine Care and Attention homes. Space syntax, a well-established method, was used to evaluate the legibility of their floor plans via calculating the integration value. RESULTS: Familiarity with Care and Attention homes did not influence the residents' satisfaction with wayfinding. The integration value had a significant impact on residents' satisfaction with wayfinding. No relationship was observed between integration value and self-reported health status. CONCLUSION: Increasing complexity in floor plans appears to negatively affect residents' wayfinding satisfaction. These data suggest that circulation patterns should be improved for better wayfinding.