Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA.

To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD) and a bifunctional R11 (RGD-NLS), which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100-280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18). More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector.

Biopolymer recovery from waste activated sludge toward self-healing mortar crack.

Activated sludge (AS) offers great potential for resource recovery considering its high organic and nutrient content. However, low recovery efficiency and high costs are directing the focus toward the high-valuable resource recovery. This study extracted 71.5 ± 5.9 mg/g VSS of alginate-like exopolysaccharides from AS (ALE/AS) and applied it to mortar as a novel biopolymer agent for crack self-healing. With a mortar crack of 120 µm, addition of 0.5 wt% ALE/AS yielded a high crack closure ratio of 86.5 % within 28 days. In comparison to commercial healing agents, marginal flexural strength reduction with ALE/AS addition (17.9 % vs 30.2-50.5 %) was demonstrated. The abundance of COO- group in GG blocks of ALE/AS resulted in a higher cross-link capacity with Ca2+, while the reduction of hydrophilic residues (e.g., COO- and OH) after complexation engendered a lower swelling capacity, which facilitated self-healing and flexural strength maintenance. Molecular dynamics (MD) revealed that lower Ca2+ diffusivity, arising from the stronger electrostatic interactions between the COO- groups and Ca2+, resulted in a high Ca2+ concentration around the cracks, leading to CaCO3 deposition and healed cracks. The outcomes of this study provided light on ALE-based mortar crack healing and presented a possibility for multi-level AS resource recovery.

Epithelial-specific deletion of FAM20A leads to short root defects.

Short Root Defects defined by a reduced ratio of root to crown, may culminate in root resorption and subsequent tooth loss, in spite of the absence of apparent symptoms. Such defects present considerable impediments to orthodontic treatment and restoration. Recent identification of Fam20a, an emergent pseudokinase, has been associated with enamel development and tooth eruption, yet its definitive role in root formation and eruption remains ambiguous. In this research, we initially ascertained that the targeted knockout of Fam20a within the epithelium led to truncated tooth roots, irregular breaks in the epithelial root sheath initiation of the WNT signaling pathway, and decreased expression of the cell polarity-related transcription factor Cdc42 in murine models. This was concomitant with the participation of the associated epithelial root sheath developmental pathways BMP2, Gli1, and Nfic. Furthermore, we observed that Fam20a predominantly affects the intraosseous eruption phase of tooth emergence. During this phase, the osteoclast peak around the mandibular first molar in cKO mice is delayed, leading to a slower formation of the eruption pathway, ultimately resulting in delayed tooth eruption in mice. The findings of this study enrich the extant knowledge regarding the role of Fam20a, suggesting its potential regulatory function in tooth root development through the WNT/ß-catenin/Cdc42 pathway.