Dynamic Interface-Assisted Rapid Self-Assembly of DNA Origami-Framed Anisotropic Nanoparticles.

The ordered arrangement of nanoparticles can generate unique physicochemical properties, rendering it a pivotal direction in the field of nanotechnology. DNA-based chemical encoding has emerged as an unparalleled strategy for orchestrating precise and controlled nanoparticle assemblies. Nonetheless, it is often time-consuming and has limited assembly efficiency. In this study, we developed a strategy for the rapid and ordered assembly of DNA origami-framed nanoparticles assisted by dynamic interfaces. By assembling Au nanoparticles (AuNPs) onto DNA origami with different sticky ends in various directions, we endowed them with anisotropic specific affinities. After assembling DNA origami-framed AuNPs onto supported lipid bilayers with freely diffusing single-stranded DNA via DNA hybridization, we found that DNA origami-framed AuNPs could form larger ordered assemblies than those in 3D solution within equivalent time frames. Furthermore, we also achieved rapid and ordered assembly of liposome nanoparticles by employing the aforementioned strategy. Our work provides a novel avenue for efficient and rapid assembly of nanoparticles across two-dimensional interfaces, which is expected to promote the application of ordered nanoparticle assemblies in sensor and biomimetic system construction.

Functional DNA as a Molecular Tool in Regulating Immunoreceptor-Ligand Interactions.

During immune responses, activating ligands would trigger dynamic spatiotemporal organization of immunoreceptors at the cell interface, governing the fate and effector functions of immune cells. To understand the biophysical mechanisms of immunoreceptor signaling, diverse tools, including DNA technologies, have been developed to manipulate receptor-ligand interactions during the immune activation process. With great capability in the controllable assembly of biomolecules, functional DNA-based precise arrangement of immune molecules at cell interfaces has provided a powerful means in revealing the principles of immunoreceptor triggering, even at the single-molecule level. In addition, precisely regulating immunoreceptor-ligand interactions with functional DNA has been applied in immunotherapies of major diseases. This Perspective will focus on the recent advances in exploring immunoreceptor signaling with functional DNA as the molecular tool as well as the applications of functional DNA mediated regulation of immunoreceptor activation. We also outline the challenges and opportunities of applying functional DNA in immune modulation and immunotherapy.

Development of non-adherent cell-enclosing domes with enzymatically cross-linked hydrogel shell.

Non-adherent cells, such as hematopoietic cells and lymphocytes, are important research subjects in medical and biological fields. Therefore, a system that enables the handling of non-adherent cells in solutions in the same manner as that of adhering cells during medium exchange, exposure to chemicals, washing, and staining in imaging applications would be useful. Here, we report a 'Cell Dome' platform in which non-adherent cells can be enclosed and grown in the cavities of about 1 mm diameter and 270µm height. The domes consist of an alginate-based hydrogel shell of 90µm thickness. Cell Domes were formed on glass plates by horseradish peroxidase-mediated cross-linking. Human leukaemia cell line K562 cells enclosed in Cell Domes were stable for 29 days with every 2-3 days of medium change. The enclosed cells grew in the cavities and were stained and differentiated with reagents supplied from the surrounding medium. Additionally, K562 cells that filled the cavities (a 3D microenvironment) were more hypoxic and highly resistant to mitomycin C than those cultured in 2D. These findings demonstrate that the 'Cell Dome' may be a promising tool for conveniently culturing and evaluating non-adherent cells.

Applications of Functional DNA Materials in Immunomodulatory Therapy.

In recent years, nanoscale or microscale functional materials derived from DNA have shown great potential for immunotherapy as superior delivery carriers. DNA nanostructures with excellent programmability and addressability enable the precise assembly of molecules or nanoparticles. DNA hydrogels have predictable structures and adjustable mechanical strength, thus being advantageous in controllable release of cargos. In addition, utilizing systematic evolution of ligands by exponential enrichment technology, a variety of DNA aptamers have been screened for specific recognition of ions, molecules, and even cells. Moreover, a wide variety of chemical modifications can further enrich the function of DNA. The unique advantages of functional DNA materials make them extremely attractive in immunomodulation. Recently, functional DNA materials-based immunotherapy has shown great potential in fighting against many diseases like cancer, viral infection, and inflammation. Therefore, in this review, we focus on discussing the progress of the applications of functional DNA materials in immunotherapy; before that, we also summarize the characteristics of the functional DNA materials descried above. Finally, we discuss the challenges and future opportunities of functional DNA materials in immunomodulatory therapy.

Injectable DNA Hydrogel-Based Local Drug Delivery and Immunotherapy.

Regulated drug delivery is an important direction in the field of medicine and healthcare research. In recent years, injectable hydrogels with good biocompatibility and biodegradability have attracted extensive attention due to their promising application in controlled drug release. Among them, DNA hydrogel has shown great potentials in local drug delivery and immunotherapy. DNA hydrogel is a three-dimensional network formed by cross-linking of hydrophilic DNA strands with extremely good biocompatibility. Benefiting from the special properties of DNA, including editable sequence and specificity of hybridization reactions, the mechanical properties and functions of DNA hydrogels can be precisely designed according to specific applications. In addition, other functional materials, including peptides, proteins and synthetic organic polymers can be easily integrated with DNA hydrogels, thereby enriching the functions of the hydrogels. In this review, we first summarize the types and synthesis methods of DNA hydrogels, and then review the recent research progress of injectable DNA hydrogels in local drug delivery, especially in immunotherapy. Finally, we discuss the challenges facing DNA hydrogels and future development directions.

Solution-processable carbon dots with efficient solid-state red/near-infrared emission.

Carbon dots (CDs) emerge as promising luminescent materials for potential applications in optoelectronics on basis of their merits including low cost, eco-friendliness and strong, color-tunable photoluminescence (PL). However, the research on solid-state emissive CDs is still at the primary stage because of the aggregation-caused quenching (ACQ) of PL and their poor film-formation ability. In this work, we produce CDs with branched-polyethylenimine (b-PEI) chemically functionalized on the surfaces. The thus newly synthesized P-CDs successfully overcome the bottleneck of ACQ effect and display efficient red and NIR emission in aggregate state. Under the excitation of 520 nm, a strong red emission (maxima of 640 nm) with a high photoluminescence quantum yield (PLQY) of 21% was observed for the P-CDs in neat film. Moreover, this design strategy endows the P-CDs with good film-formation ability via solution spin-coating, which significantly increases its value for the film-based optoelectronic devices.

Influence of Hydrogen Peroxide-Mediated Cross-Linking and Degradation on Cell-Adhesive Gelatin Hydrogels.

Hydrogen peroxide (H2O2) is widely used for the gelation of aqueous solutions of gelatin derivatives with phenolic hydroxyl groups (Gelatin-Ph) catalyzed by horseradish peroxidase (HRP). Apart from this, H2O2 is known to cause degradation/depolymerization of various polymers. Here, we prepared Gelatin-Ph hydrogels from solutions containing Gelatin-Ph and HRP by continuously supplying H2O2 from the gas phase and investigated the mechanical properties of resultant hydrogels and the behaviors of rat fibroblast and human adipose-derived stem cells on them. Young's modulus of the hydrogel obtained from 5 w/v % Gelatin-Ph and 1 and 5 U/mL HRP increased when the exposure time to air containing H2O2 (16 ppm) was extended from 15 to 30 min. However, further prolonging the exposure time to 60 min reduced Young's modulus to the same magnitude as for the hydrogels exposed to air containing H2O2 for 15 min. Interestingly, the cell length and aspect ratio of the cells continued to increase, as the exposure time was extended, without reflecting the decrease in Young's modulus. These results indicate that when preparing Gelatin-Ph hydrogels through HRP/H2O2-mediated gelation, it is necessary to consider the effect of the degradation of Gelatin-Ph caused by H2O2 on the mechanical properties of the resultant hydrogels and the behaviors of cells on them.

Peroxidase-catalyzed microextrusion bioprinting of cell-laden hydrogel constructs in vaporized ppm-level hydrogen peroxide.

Hydrogels were prepared by contacting air containing 10-50 ppm H2O2 with an aqueous solution containing polymer(s) possessing phenolic hydroxyl (Ph) moieties (polymer-Ph) and horseradish peroxidase (HRP). In this system, HRP catalyzes cross-linking of the Ph moieties by consuming H2O2 diffused from the air. The hydrogelation rate and mechanical properties of the resultant hydrogels can be tuned by controlling the H2O2 concentration in air, the exposure time of the air containing H2O2 to the solution containing polymer-Phs and HRP, and the HRP concentration. The shortest hydrogelation time of the solution stirred in air containing 16 ppm H2O2 was 6 s. Based on these findings, this hydrogelation system was applied to microextrusion bioprinting, in which bioink containing polymer-Phs, HRP, and cells were extruded into air containing H2O2. The superior cytocompatibility of the bioprinting method was confirmed by more than 90% viability, migration, and the spreading of mouse fibroblast 10T1/2 cells enclosed in the bioprinted hydrogels composed of derivatives of hyaluronic acid and gelatin, both possessing Ph moieties. These results demonstrate the great potency of HRP-catalyzed hydrogelation consuming H2O2 supplied in surrounding air for various biomedical applications, especially bioprinting.

Quantitative structure-activity relationship for the partition coefficient of hydrophobic compounds between silicone oil and air.

The silicon oil-air partition coefficients (KSiO/A) of hydrophobic compounds are vital parameters for applying silicone oil as non-aqueous-phase liquid in partitioning bioreactors. Due to the limited number of KSiO/A values determined by experiment for hydrophobic compounds, there is an urgent need to model the KSiO/A values for unknown chemicals. In the present study, we developed a universal quantitative structure-activity relationship (QSAR) model using a sequential approach with macro-constitutional and micromolecular descriptors for silicone oil-air partition coefficients (KSiO/A) of hydrophobic compounds with large structural variance. The geometry optimization and vibrational frequencies of each chemical were calculated using the hybrid density functional theory at the B3LYP/6-311G** level. Several quantum chemical parameters that reflect various intermolecular interactions as well as hydrophobicity were selected to develop QSAR model. The result indicates that a regression model derived from logKSiO/A, the number of non-hydrogen atoms (#nonHatoms) and energy gap of ELUMO and EHOMO (ELUMO-EHOMO) could explain the partitioning mechanism of hydrophobic compounds between silicone oil and air. The correlation coefficient R2 of the model is 0.922, and the internal and external validation coefficient, Q2LOO and Q2ext , are 0.91 and 0.89 respectively, implying that the model has satisfactory goodness-of-fit, robustness, and predictive ability and thus provides a robust predictive tool to estimate the logKSiO/A values for chemicals in application domain. The applicability domain of the model was visualized by the Williams plot.

Spasmolytic activity of Aquilariae Lignum Resinatum extract on gastrointestinal motility involves muscarinic receptors, calcium channels and NO release.

CONTEXT: Aquilariae Lignum Resinatum (ALR), the dry rhizome of Aquilaria agallocha R. (Thymelaeaeeae), has been widely used to treat emesis, stomachache and gastrointestinal dysfunction. OBJECTIVE: This study evaluates the effects of ALR methanol extract on gastrointestinal motility (GIM) and possible mechanisms of the action involved. MATERIALS AND METHODS: In vivo, the study evaluated the effects of ALR (200-800 mg/kg) on gastric emptying and small intestinal motility in normal and neostigmine-induced adult KM mice. The in vitro effects of ALR (0.2-1.6 mg/mL) on GIM were performed on isolated jejunum of Wistar rats, pretreated with acetylcholine (ACh), KCl, CaCl2, and pre-incubation with l-NAME (a selective inhibitor of the nitric oxide synthase). RESULTS: In vivo, ALR (800 mg/kg) decreased gastric emptying (70.82 ± 9.81%, p < 0.01, compared with neostigmine group 91.40 ± 7.81%), small intestinal transit (42.82 ± 3.82%, p < 0.01, compared with neostigmine group 85.53 ± 5.57%). In vitro, ALR concentration dependently decreased the contractions induced by ACh (10-5 M) and KCl (60 mM) with respective EC50 values of 0.35 and 0.32 mg/mL. The Ca2+ concentration-response curves were shifted by ALR to the right, similar to that caused by verapamil (the positive). The spasmolytic activity of ALR was inhibited by pre-incubation with l-NAME. DISCUSSION AND CONCLUSIONS: ALR played a spasmolytic role in GIM, which is probably mediated through inhibition of muscarinic receptors, blockade of Ca2+ influx and NO release. This is the first study presenting a comprehensive description of the effects of ALR on GIM.

New Triterpenoid Saponins from the Herb Hylomecon japonica.

Background: Hylomecon japonica, a plant of the Papaveraceae family which is well-known for the alkaloids they produce, is a perennial plant widely distributed in the northeast, central and east regions of China. Although a variety of chemical constituents, including alkaloids, flavonoids, and megastigmoids, have been isolated from H. japonica, the investigation of saponins in H. japonica has not been reported until now. Methods: Various separation techniques, including polyporous resin column chromatography, silica gel column chromatography and hemi-preparative HPLC were applied to the isolation of triterpenoid saponins, and chemical methods such as acid hydrolysis and spectroscopic methods including HRESIMS and NMR were applied to their structure elucidation, and the XTT reduction method was used to assay cytotoxicity. Results: Two new triterpenoid saponins, named hylomeconoside A (1) and B (2) which were identified as 3-O-ß-d-galactopyranosyl-(1→2)-ß-d-glucuronopyranosyl-gypsogenin-28-O-ß-d-xylopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-ß-d-quinovopyranoside (1) and 3-O-ß-d-galactopyranosyl-(1→2)-ß-d-glucuronopyranosyl-gypsogenin-28-O-ß-d-xylopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (2), and two known triterpenoid saponins identified as dubioside C (3) and lucyoside P (4) on the basis of spectroscopic and chemical evidence, were isolated from H. japonica. Compound 1 exhibited moderate cytotoxicity on MGC-803 and HL-60 cells, with IC50 values of 43.8 and 32.4 µg·mL-1, respectively. Conclusions: Compounds 1 and 2 are new saponins, and 1 is considered to be one of the antitumor principles in this plant. This is the first time that triterpenoid saponins have been isolated from plants of the Papaveraceae family.

Pheonolic Compounds from the Fruits of Viburnum sargentii Koehne.

Seven phenolic compounds were isolated from the fruits of Viburnum sargentii Koehne by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as (-)-Epicatechin (1), 5,7,4'-trihydroxy-flavonoid-8-C-ß-D-glucopyranoside (2), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propane-diol (erythro) (3), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (threo) (4), (R)-4-hydroxylphenol O-(6-O-oleuropeoyl)-ß-D-glucopyranoside (5), (R)-3-methoxy-4-hydroxylphenol O-(6-O-oleuropeoyl)-ß-D-glucopyranoside (6), quercetin-3-O-rutinoside (7). Compounds 5 and 6 are new monoterpene phenolic glycosides, compounds 1, 3 and 4 were isolated from the Viburnum genus for the first time, and compounds 2 and 7 from the Viburnum sargentii Koehne for the first time. Compounds 1-7 were also assayed for their antioxidant activities with DPPH free radicals.