Supragel-mediated efficient generation of pancreatic progenitor clusters and functional glucose-responsive islet-like clusters.

Although several synthetic hydrogels with defined stiffness have been developed to facilitate the proliferation and maintenance of human pluripotent stem cells (hPSCs), the influence of biochemical cues in lineage-specific differentiation and functional cluster formation has been rarely reported. Here, we present the application of Supragel, a supramolecular hydrogel formed by synthesized biotinylated peptides, for islet-like cluster differentiation. We observed that Supragel, with a peptide concentration of 5 mg/mL promoted spontaneous hPSCs formation into uniform clusters, which is mainly attributable to a supporting stiffness of ∼1.5 kPa as provided by the Supragel matrix. Supragel was also found to interact with the hPSCs and facilitate endodermal and subsequent insulin-secreting cell differentiation, partially through its components: the sequences of RGD and YIGSR that interacts with cell membrane molecules of integrin receptor. Compared to Matrigel and suspension culturing conditions, more efficient differentiation of the hPSCs was also observed at the stages 3 and 4, as well as the final stage toward generation of insulin-secreting cells. This could be explained by 1) suitable average size of the hPSCs clusters cultured on Supragel; 2) appropriate level of cell adhesive sites provided by Supragel during differentiation. It is worth noting that the Supragel culture system was more tolerance in terms of the initial seeding densities and less demanding, since a standard static cell culture condition was sufficient for the entire differentiation process. Our observations demonstrate a positive role of Supragel for hPSCs differentiation into islet-like cells, with additional potential in facilitating germ layer differentiation.

Facilitated transport of microplastics and nonylphenol in porous media with variations in physicochemical heterogeneity.

Nonylphenol (Noph) has garnered worldwide concern as a typical endocrine disruptor due to its toxicity, estrogenic properties, and widespread contamination. To better elucidate the interaction of Noph with ubiquitously existing microplastics (MPs) and the potential interdependence of their transport behaviors, batch adsorption and column experiments were conducted, paired with mathematical modeling. Compared with sand, MPs and soil colloids show stronger adsorption affinity for Noph due to the formation of hydrogen bonding and the larger numbers of interaction sites that are available on solid surfaces. Limited amount of soil-colloid coating on sand grains significantly influenced transport behaviors and the sensitivity to solution chemistry. These coatings led to a monotonic increase in Noph retention and a nonmonotonic MPs retention in single systems because of the altered physicochemical properties. The mobility of both MPs and Noph was enhanced when they coexisted, resulting from their association, increased electrostatic repulsion, and competition on retention sites. Limited release of MPs and Noph (under reduced ionic strength (IS) and increased pH) indicated strong interactions in irreversible retention. The retention and release of Noph were independent of IS and solution pH. A one-site model with a blocking term and a two-site kinetic model well described the transport of MPs and Noph, respectively. Our findings highlight the essential roles of coexisting MPs and Noph on their transport behaviors, depending on their concentrations, IS, and physicochemical properties of the porous media. The new knowledge from this study refreshes our understanding of the co-transport of MPs and organic contaminants such as Noph in the subsurface.

Framework Nucleic Acids Enabled Pulmonary Artery Endothelial Cell Growth Inhibition by Targeting microRNA-152.

Pulmonary artery vascular endothelial dysfunction plays a pivotal role in the occurrence and progression of pulmonary vascular remodeling (PVR). To address this, aberrantly expressed non-coding microRNAs (miRNAs) are excellent therapeutic targets in human pulmonary artery endothelial cells (HPAECs). Here, we discovered and validated the overexpression of miRNA-152 in HPAECs under hypoxia and its role in endothelial cell dysfunction. We constructed a framework nucleic acid nanostructure that harbors six protruding single-stranded DNA segments that can fully hybridize with miRNA-152 (DNT-152). DNT-152 was efficiently taken up by HPAECs with increasing time and concentration; it markedly induced apoptosis, and inhibited HPAEC growth under hypoxic conditions. Mechanistically, DNT-152 silenced miRNA-152 expression and upregulated its target gene Meox2, which subsequently inhibited the AKT/mTOR signaling pathway. These results indicate that miRNA-152 in HPAECs may be an excellent therapeutic target against PVR, and that framework nucleic acids with carefully designed sequences are promising nanomedicines for noncancerous cells and diseases.

Cotransport of micro- and nano-plastics with chlortetracycline hydrochloride in saturated porous media: Effects of physicochemical heterogeneities and ionic strength.

Global production and use of plastics have resulted in the wide dissemination of micro- and nano-plastics (MNPs) to the natural environment. Potentially acting as a vector, the role of MNPs on the fate and transport of environmental pollutants (e.g., antibiotics such as chlortetracycline hydrochloride; CTC) has garnered global concern recently. Herein, the cotransport of MNPs and CTC in columns packed with uncoated sand or soil colloid-coated sand (SCCS) under different degrees of physicochemical heterogeneity and ionic strength was systematically explored. Our results show that MNPs and CTC inhibit the transport of each other when they coexist. The adsorption of CTC onto sand grains, soil colloids, and MNPs, as well as the aggregation of MNPs in the presence of CTC could be the major contributors to the enhanced retention of CTC and MNPs. In SCCS with different degrees of soil colloid coating, the adsorption of CTC on soil colloids is critical to influence the transport of CTC, and the nonlinear retention of MNPs to soil colloids is mainly attributed to the alteration of collector surface roughness by soil colloids. High ionic strength slightly facilitates CTC transport due to the competition for adsorption sites and the formation of CTC macromolecules, but significantly inhibits MNPs transport by suppressing the electrostatic double layers based on colloid stability theory. Consequently, the cotransport of MNPs and CTC is governed by the coupled interplay of collector surface roughness and chemical heterogeneity, due to the soil colloid coatings and the adsorbed CTC on the surfaces associated with solution chemistries such as ionic strength. Increased cotransport of MNPs and CTC occurred under a higher concentration of MNPs due to a larger number of adsorption sites for CTC. Our findings advance the current understanding of the complex cotransport of MNPs and antibiotics in the environment. This information is valuable for understanding contaminant fate and formulating strategies for environmental remediation due to the contamination of MNPs and co-occurring contaminants.

CLAVATA1-type receptor-like kinase CsCLAVATA1 is a putative candidate gene for dwarf mutation in cucumber.

Dwarf mutations have played vital roles in elucidating the regulatory molecular mechanisms of plant height. In this study, we identified a mutant named Csdw, whose mutagenesis was induced by ethyl methyl sulfonate in cucumber, and this mutant exhibited a dwarf phenotype with a reduced internode length because of the reduction of cell division in the main stem. The dwarf phenotype of Csdw could be partially rescued through GA3 application, and endogenous GA3 levels from the stem of Csdw decreased distinctly. Genetic analysis showed that Csdw was attributed to a recessive gene. The MutMap and Kompetitive Allele Specific PCR genotyping results revealed that Csa3G872760 (CsCLAVATA1), encoding a CLAVATA1-type receptor-like kinase, was a putative candidate gene for dwarf mutation in cucumber. The expression of CsCLAVATA1 in the stem of Csdw was lower than that of wild-type plants. Therefore, CsCLAVATA1 could regulate the dwarf phenotype in cucumber.

Cscs encoding chorismate synthase is a candidate gene for leaf variegation mutation in cucumber.

Variegation is a frequently observed genetic phenomenon in landscaping. In this study, an ethyl methanesulfonate induced variegated leaf (Csvl) mutant in cucumber (Cucumis sativus L.) was identified. The Csvl mutant displayed green-yellow-white variegation phenotype throughout the whole growth cycle, while the leaf of wild type plants was normal green. The photosynthetic pigment contents and photosynthetic parameters of Csvl was significantly lower than wild type. The cytology observation results showed that the mesophyll cells of Csvl mutant contained defective chloroplasts. Genetic analysis indicated that variegated leaf phenotype was monogenic recessive inheritance. MutMap and genotyping results revealed that Csa6G405290 (Cscs), encoding chorismate synthase, was the candidate gene for variegated leaf mutant in cucumber. The expression level of Cscs was similar between wild type and variegated leaf mutant leaves. Transcriptome profile analysis of leaves of Csvl mutant identified 183 candidate genes involved in variegated leaf development in cucumber, including genes that encode heat shock protein, zinc finger protein. Cscs may regulate variegated leaf in cucumber by interacting with these genes. In a word, these results revealed that Cscs might regulate the variegated leaf phenotype in cucumber.