Bis-Alkylureido Imidazole Artificial Water Channels.

Nature creates aquaporins to effectively transport water, rejecting all ions including protons. Aquaporins (AQPs) has brought inspiration for the development of Artificial Water Channels (AWCs). Imidazole-quartet (I-quartet) was the first AWC that enabled to self-assemble a tubular backbone for rapid water and proton permeation with total ion rejection. Here, we report the discovery of bis-alkylureido imidazole compounds, which outperform the I-quartets by exhibiting ≈3 times higher net and single channel permeabilities (107 H2 O/s/channel) and a ≈2-3 times lower proton conductance. The higher water conductance regime is associated to the high partition of more hydrophobic bis-alkylureido channels in the membrane and to their pore sizes, experiencing larger fluctuations, leading to an increase in the number of water molecules in the channel, with decreasing H-bonding connectivity. This new class of AWCs will open new pathways toward scalable membranes with enhanced water transport performances.

Complexation Preferences of Dynamic Constitutional Frameworks as Adaptive Gene Vectors.

The growing applications of therapeutic nucleic acids requires the concomitant development of vectors that are optimized to complex one type of nucleic acid, forming nanoparticles suitable for further trafficking and delivery. While fine-tuning a vector by molecular engineering to obtain a particular nanoscale organization at the nanoparticle level can be a challenging endeavor, we turned the situation around and instead screened the complexation preferences of dynamic constitutional frameworks toward different types of DNAs. Dynamic constitutional frameworks (DCF) are recently-identified vectors by our group that can be prepared in a versatile manner through dynamic covalent chemistry. Herein, we designed and synthesized 40 new DCFs that vary in hydrophilic/hydrophobic balance, number of cationic headgroups. The results of DNA complexation obtained through gel electrophoresis and fluorescent displacement assays reveal binding preferences of different DCFs toward different DNAs. The formation of compact spherical architectures with an optimal diameter of 100-200 nm suggests that condensation into nanoparticles is more effective for longer PEG chains and PEI groups that induce a better binding performance in the presence of DNA targets.

Structure-Activity Relationships in Nucleic-Acid-Templated Vectors Based on Peptidic Dynamic Covalent Polymers.

The use of nucleic acids as templates, which can trigger the self-assembly of their own vectors represent an emerging, simple and versatile, approach toward the self-fabrication of tailored nucleic acids delivery vectors. However, the structure-activity relationships governing this complex templated self-assembly process that accompanies the complexation of nucleic acids remains poorly understood. Herein, the class of arginine-rich dynamic covalent polymers (DCPs) composed of different monomers varying the number and position of arginines were studied. The combinations that lead to nucleic acid complexation, in saline buffer, using different templates, from short siRNA to long DNA, are described. Finally, a successful peptidic DCP featuring six-arginine repeating unit that promote the safe and effective delivery of siRNA in live cancer cells was identified.

Engineering PD-L1 Cellular Nanovesicles Encapsulating Epidermal Growth Factor for Deep Second-Degree Scald Treatment.

Scars are common and intractable consequences after scalded wound healing, while monotherapy of epidermal growth factors does not solve this problem. Maintaining the stability of epidermal growth factors and promoting scarless healing of wounds is paramount. In this study, engineering cellular nanovesicles overexpressing PD-L1 proteins, biomimetic nanocarriers with immunosuppressive efficacy, were successfully prepared to encapsulate epidermal growth factors for maintaining its bioactivity. Remarkably, PD-L1 cellular nanovesicles encapsulating epidermal growth factors (EGF@PDL1 NVs) exerted desired therapeutic effect by attenuating the overactivation of T cell immune response and promoting skin cells migration and proliferation. Hence, EGF@PD-L1 NVs promoted wound healing and prevented scarring in deep second-degree scald treatment, demonstrating a better effect than using individual PD-L1 NVs or EGF. This research proved that EGF@PD-L1 NVs is considered an innovative and thorough therapy of deep second-degree scald.

Establishment of reference (housekeeping) genes via quantitative real-time PCR for investigation of the genomic basis of abiotic stress resistance in Psammochloa villosa (Poaceae).

Psammochloa villosa is a desert plant growing in Northwest China with considerable resistance to abiotic stress, including drought, cold, and salt. To facilitate future studies of stress resistance in Psammochloa villosa, we sought to establish a suite of reference (or housekeeping) genes for utilization within future gene expression studies. Specifically, we selected nine candidate genes based on prior studies and new transcriptomic data for P. villosa, and we evaluated their expression stability in three different tissues of P. villosa under different treatments simulating abiotic stress conditions using four different bioinformatics assessments. Our results showed that TIP41 (TIP41-like family protein) was the most stable reference gene in drought- and salt-stressed leaves and salt-stressed stems, ELF-1α (elongation factor 1-α) was the most stable in cold-stressed leaves and drought- and salt-stressed roots, ACT (actin) was the most stable in drought-stressed stems, TUA (α-tubulin) was the most stable in cold-stressed stems, and 18S rRNA (18S ribosomal RNA) was the most stable in cold-stressed roots. Additionally, we tested the utility of these candidate reference genes to detect the expression pattern of P5CS (Δ1-pyrroline-5-carboxylate synthetase), which is a drought-related gene. This study is the first report on selecting and validating reference genes of P. villosa under various stress conditions and will benefit future investigations of the genomic mechanisms of stress resistance in this ecologically important species.