Delivery of mRNA for regulating functions of immune cells.

Abnormal immune cell functions are commonly related to various diseases, including cancer, autoimmune diseases, and infectious diseases. Messenger RNA (mRNA)-based therapy can regulate the functions of immune cells or assign new functions to immune cells, thereby generating therapeutic immune responses to treat these diseases. However, mRNA is unstable in physiological environments and can hardly enter the cytoplasm of target cells; thus, effective mRNA delivery systems are critical for developing mRNA therapy. The two mRNA vaccines of Pfizer-BioNTech and Moderna have demonstrated that lipid nanoparticles (LNPs) can deliver mRNA into dendritic cells (DCs) to induce immunization against severe acute respiratory syndrome coronavirus 2, which opened the floodgates to the development of mRNA therapy. Apart from DCs, other immune cells are promising targets for mRNA therapy. This review summarized the barriers to mRNA delivery and advances in mRNA delivery for regulating the functions of different immune cells.

[Integrin activation, focal adhesion maturation and tumor metastasis].

Integrins are a large family of heterodimeric cell adhesion molecules composed of α and ß subunits. Through interaction with their specific ligands, integrins mediate cell-cell and cell-extracellular matrix interactions. Via outside-in signaling, integrins can recruit cytoplasmic proteins to their intracellular domains and then cluster into supramolecular structures and trigger downstream signaling. Integrin activation is associated with a global conformation rearrangement from bent to extended in ectodomains and the separation of α and ß subunit cytoplasmic domains. During cell migration, integrins regulate the focal adhesion dynamics and transmit forces between the extracellular matrix and the cell cytoskeleton. In tumor microenvironment, integrins on multiple kinds of cells could be activated, which modulates cell migration into tumor and contributes to angiogenesis and tumor metastasis. Here, we review the mechanism of integrin activation, dynamics of focal adhesions during cell migration and tumor metastasis.

Professional perspectives on providing recovery-oriented services in Taiwan: a qualitative study.

BACKGROUND: The experiences of professionals in well-established recovery-oriented programs are valuable for professionals in similar practice settings. This study explored professionals' experiences with providing recovery-oriented services in community psychiatric rehabilitation organizations. METHODS: Semi-structured interviews were conducted with 14 professionals from five recovery-oriented psychiatric rehabilitation organizations in Taiwan. The interviews were recorded and transcribed verbatim. Thematic analysis was used for the qualitative data analysis. RESULTS: The analyses documented three main themes with 13 subthemes. Recovery-oriented service implementation included seven subthemes: Enabling clients to set their own goals and make decisions, using a strengths-based approach, establishing partnerships with clients, improving individuals' self-acceptance, encouraging community participation, seeking family, peer, and organizational support, and building team collaboration. Problems with implementing recovery-oriented services included limited policy and organizational support, a lack of understanding of recovery among professionals, stigma, clients' lack of motivation or self-confidence in their own ability to achieve recovery, and passive or overprotective family members. Strategies to resolve implementation problems included policy changes and organizational support, improving the recovery competence and confidence of professionals, and family and public education. CONCLUSIONS: To date, this is the first known study examining the perspectives of mental health professionals who have experience implementing recovery-oriented services in Asia. The participants identified family collaboration, anti-stigma efforts, and changes in policy and attitudes as critical to successful implementation and delivery of recovery-oriented services.

Formal syntheses of (-)-isoretronecanol, (+)-laburnine, and a concise enantioselective synthesis of (+)-turneforcidine.

The synthesis of functionalized pyroglutamates 15 and 16 could be achieved by the application of recently developed diastereodivergent asymmetric Michael addition reaction of iminoglycinate 7 to ethyl γ-silyloxycrotonate with >98:<2 diastereoselectivity followed by hydrolysis and lactamization. Formal syntheses of (-)-isoretronecanol and (+)-laburnine as well as a concise enantioselective synthesis of (+)-turneforcidine could be achieved from functionalized pyroglutamates 15 or 16.