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Abstract Recently, lipid nanoparticles (LNPs)‐based mRNA delivery has been approved by the FDA for SARS‐CoV‐2 vaccines. However, there are still considerable points for improvement in LNPs. Especially, local administration of LNPs‐formulated mRNA can cause off‐target translation of mRNA in distal organs which can induce unintended adverse effects. With the hypothesis that large and rigid nanoparticles can be applied to enhance retention of nanoparticles at the injection site, a polyethyleneimine (PEI)‐coated porous silica nanoparticles (PPSNs)‐based mRNA delivery platform is designed. PPSNs not only facilitate localized translation of mRNA at the site of injection but also prolonged protein expression. It is further demonstrated that the development of a highly efficacious Zika virus (ZIKV) vaccine using mRNA encoding full‐length ZIKV pre‐membrane (prM) and envelope (E) protein delivered by PPSNs. The ZIKV prME mRNA‐loaded PPSNs vaccine elicits robust immune responses, including high levels of neutralizing antibodies and ZIKV E‐specific T cell responses in C57BL/6 mice. Moreover, a single injection of prME‐PPSNs vaccine provided complete protection against the ZIKV challenge in mice.

Molecular chaperones play an important part in protein folding and delivery in nature. Here, the authors report on the creation of a synthetic chaperone to control the folding of therapeutic peptides from random coil to alpha helix and demonstrate enhanced therapeutic potential in an in vivo tumour model.

The article presents a study which investigates the embryonic-abembryonic (Em-Ab) axis of the blastocyst in the porcine parthenogenetic embryo of a pig. It examines whether porcine embryos would exist as an intrinsic property of oocyte itself, and describes the fate of an individual blastomere from a 2-cell-stage parthenogenetic porcine embryo. It mentions that porcine parthenotes were used in investigating the Em-Ab axis in the pig to prevent the topological change caused by polyspermy, and to avoid the influences of sperm entry position. Results show that the fate of an individual blastomere of the porcine parthenogenetic embryo at the 2-cell stage may be an intrinsic property of the oocyte itself.

The article informs about research on discovery of direct-acting antiviral agents with a graphene-based fluorescent nanosensor. Topics discussed include direct-acting drugs exist for the treatment against dengue virus (DV) infection, which can develop into life-threatening diseases; and development of an RNA-based graphene biosensor system [RNA nano-graphene oxide system (RANGO)] to enable the fluorescence-based quantitative analysis of the RdRp enzyme activity.

Although an in vitro 3D environment cannot completely mimic the in vivo tumor site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the study of cancer cell behaviors and the screening of anti-metastatic reagents with a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions (including cell density, extracellular acidity, or hypoxia as mimics for a continuous tumor growth) reduced JNKs, enhanced TGFβ1/Smad signaling activity, induced Snail1, and reduced cortactin expression. The reduced JNKs activity blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1-MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1 expression. Snail1 then repressed cortactin expression, causing reduced invadopodia formation and prominent localization of MT1-MMP at perinuclear regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation and invasion in 3D collagen I upon JNKs inhibition. These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents. [ABSTRACT FROM AUTHOR]

&agr;-ENO1ase (ENO1) is a multifunctional glycolytic enzyme expressed abundantly in the cytosol. It has been implicated in autoimmune and inflammatory diseases. Serum Abs against ENO1 were reported in rheumatoid arthritis (RA). Cell-surface expression of ENO1 has been found to be increased rapidly in response to inflammatory stimuli, but its expression and function has not been reported in RA. In this study, we show that cell-surface expression of ENO1 is increased on monocytes and macrophages isolated from RA patients but not on those from osteoarthritis patients, and Ab against ENO1 can stimulate these cells to produce higher amounts of proinflammatory mediators, such as TNF-&agr;, IL-1 ot/&bgr;, IFN-&ggr;, and PGE2 via p38 MAPK and NF-KB pathway. The frequency of ENO1-positive cells in synovial fluid mononuclear cells was higher than PBMCs. ENO1-positive cells were also found in the inflamed synovium from RA patients and arthritic ankle tissues of mice with collagen-induced arthritis. Taken together, these findings suggest that Abs against ENO1 present in RA sera may stimulate monocytes and macrophages expressing cellsurface ENO1 and contribute to production of proinflammatory mediators during the effector phase of synovial inflammation. [ABSTRACT FROM AUTHOR]