Oral Administration Properties Evaluation of Three Milk-Derived Extracellular Vesicles Based on Ultracentrifugation Extraction Methods.

Milk-derived extracellular vesicles (M-EVs) are low-cost, can be prepared in large quantities, and can cross the gastrointestinal barrier for oral administration. However, the composition of milk is complex, and M-EVs obtained by different extraction methods may affect their oral delivery. Based on this, a new method for extracting M-EVs based on cryogenic freezing treatment (Cryo-M-EVs) is proposed and compared with the previously reported acetic acid treatment (Acid-M-EVs) method and the conventional ultracentrifugation method (Ulltr-M-EVs). The new method simplifies the pretreatment step and achieves 25-fold and twofold higher yields than Acid-M-EVs and Ulltr-M-EVs. And it is interesting to note that Cryo-M-EVs and Acid-M-EVs have higher cellular uptake efficiency, and Cryo-M-EVs present the best transepithelial transport effect. After oral administration of the three M-EVs extracted by three methods in mice, Cryo-M-EVs effectively successfully cross the gastrointestinal barrier and achieve hepatic accumulation, whereas Acid-M-EVs and Ultr-M-EVs mostly reside in the intestine. The M-EVs obtained by the three extraction methods show a favorable safety profile at the cellular as well as animal level. Therefore, when M-EVs obtained by different extraction methods are used for oral drug delivery, their accumulation properties at different sites can be utilized to better deal with different diseases.

Gold nanoparticles combat enveloped RNA virus by affecting organelle dynamics.

Enveloped RNA viruses are a group of viruses with an outer membrane derived from a host cell and a genome consisting of ribonucleic acid (RNA). These viruses rely on host cell machinery and organelles to replicate and assemble new virus particles. However, the interaction between viruses and host organelles may be disrupted by nanomaterials, such as gold nanoparticles (AuNPs) with unique physical and chemical properties. In this study, we investigated the effects of AuNPs with different surface charge properties on the subcellular structure and function of mammalian cells, and their effects on two representative enveloped RNA viruses: lentivirus and human coronavirus OC43 (HCoV- OC43) antiviral potential. By comparing the subcellular effects of AuNPs with different surface charge properties, we found that treatment with AuNPs with positive surface charges induced more significant disruption of subcellular structures than neutrally charged AuNPs and negatively charged AuNPs, mainly manifested in lysosomes and Cytoskeletal disorders. The antiviral effect of the surface positively charged AuNPs was further evaluated using lentivirus and HCoV-OC43. The results showed that AuNPs had a significant inhibitory effect on both lentivirus and HCoV-OC43 without obvious side effects. In conclusion, our study provides insights into the mechanism of action and biocompatibility of AuNP in biological systems, while supporting the potential of targeting organelle dynamics against enveloped RNA viruses.

Tunable Mechanical Response of Self-Assembled Nanoparticle Superlattices.

Self-assembled nanoparticle superlattices (NPSLs) are an emergent class of self-architected nanocomposite materials that possess promising properties arising from precise nanoparticle ordering. Their multiple coupled properties make them desirable as functional components in devices where mechanical robustness is critical. However, questions remain about NPSL mechanical properties and how shaping them affects their mechanical response. Here, we perform in situ nanomechanical experiments that evidence up to an 11-fold increase in stiffness (∼1.49 to 16.9 GPa) and a 5-fold increase in strength (∼88 to 426 MPa) because of surface stiffening/strengthening from shaping these nanomaterials via focused-ion-beam milling. To predict the mechanical properties of shaped NPSLs, we present discrete element method (DEM) simulations and an analytical core-shell model that capture the FIB-induced stiffening response. This work presents a route for tunable mechanical responses of self-architected NPSLs and provides two frameworks to predict their mechanical response and guide the design of future NPSL-containing devices.

Nanomedicine for T-Cell Mediated Immunotherapy.

T-cell immunotherapy offers outstanding advantages in the treatment of various diseases, and with the selection of appropriate targets, efficient disease treatment can be achieved. T-cell immunotherapy has made great progress, but clinical results show that only a small proportion of patients can benefit from T-cell immunotherapy. The extensive mechanistic work outlines a blueprint for using T cells as a new option for immunotherapy, but also presents new challenges, including the balance between different fractions of T cells, the inherent T-cell suppression patterns in the disease microenvironment, the acquired loss of targets, and the decline of T-cell viability. The diversity, flexibility, and intelligence of nanomedicines give them great potential for enhancing T-cell immunotherapy. Here, how T-cell immunotherapy strategies can be adapted with different nanomaterials to enhance therapeutic efficacy is discussed. For two different pathological states, immunosuppression and immune activation, recent advances in nanomedicines for T-cell immunotherapy in diseases such as cancers, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, and diabetes are summarized. With a focus on T-cell immunotherapy, this review highlights the outstanding advantages of nanomedicines in disease treatment, and helps advance one's understanding of the use of nanotechnology to enhance T-cell immunotherapy.

Large scale self-assembly of plasmonic nanoparticles on deformed graphene templates.

Hierarchical heterostructures of two-dimensional (2D) nanomaterials are versatile platforms for nanoscale optoelectronics. Further coupling of these 2D materials with plasmonic nanostructures, especially in non-close-packed morphologies, imparts new metastructural properties such as increased photosensitivity as well as spectral selectivity and range. However, the integration of plasmonic nanoparticles with 2D materials has largely been limited to lithographic patterning and/or undefined deposition of metallic structures. Here we show that colloidally synthesized zero-dimensional (0D) gold nanoparticles of various sizes can be deterministically self-assembled in highly-ordered, anisotropic, non-close-packed, multi-scale morphologies with templates designed from instability-driven, deformed 2D nanomaterials. The anisotropic plasmonic coupling of the particle arrays exhibits emergent polarization-dependent absorbance in the visible to near-IR regions. Additionally, controllable metasurface arrays of nanoparticles by functionalization with varying polymer brushes modulate the plasmonic coupling between polarization dependent and independent assemblies. This self-assembly method shows potential for bottom-up nanomanufacturing of diverse optoelectronic components and can potentially be adapted to a wide array of nanoscale 0D, 1D, and 2D materials.

[Nutrient Exchange Between Meixi River and Yangtze River Due to the Typical Interaction Process of the Three Gorges Reservoir and Its Tributary].

Frequent algal blooms have been observed in the Meixi bay of the Three Gorges Reservoirs (TGR) since its initial filling. In order to understand the effects of intrusions from Changjiang mainstream on the nutrient supply of the Meixi Bay, a detailed field monitoring was conducted from August 2012 to July 2013. The results showed that there were significant intrusions from the mainstream to the Meixi Bay during the different water level scheduling periods of the TGR. As a result, the invading flow from the mainstream of the Changjiang caused a significant effect on the nutrient distribution in the Meixi River. Annually, the mainstream transportednet fluxes of 5 478.02 t DIN, 234.04 t DIP and 5 935.22 t DSi to the Meixi Bay, which were 2.37 times, 4.32 times and 1.33 times of the corresponding fluxes from the upstream, respectively. The influence on the nutrient distributions was not only limited in the estuary area but also in the upper reaches, the supply of DIP changed the nutrient structure and relieved the P restrictions on phytoplankton growth.

[Partial pressure and diffusion flux of dissolved carbon dioxide in the mainstream and tributary of the central Three Gorges Reservoir in summer].

This study investigated the partial pressure of CO2 (pCO2) in the mainstream of the Three Gorges Reservoir and its tributary (Meixi River) in May 2013. Results showed that pCO2 in the surface water of the Meixi River and mainstream of the Three Gorges Reservoir was 6.8-7.5 Pa and 201.4-210.2 Pa, respectively. At the mixing area between the Meixi River and the mainstream of Changjiang, the lowest value of pCO2 in surface water was 53.5 Pa, and pCO2 gradually increased downwardly. Below 3 m in depth, pCO2 kept the stable value of around 210 Pa. Based on the calculation results, the emission flux of CO2 in the Meixi River and the mainstream of the central Three Gorges Reservoir was about -7.48 mmol x (m2 x d)(-1) and 39.58 mmol x (m2 x d)(-1), respectively. These results showed that the Meixi River is a sink for atmospheric CO2, and the mainstream of the Three Gorges Reservoir is a source for atmospheric CO2.