Repairing Mechanisms for Distal Airway Injuries and Related Targeted Therapeutics for Chronic Lung Diseases.

Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), involve progressive and irreversible destruction and pathogenic remodeling of airways and have become the leading health care burden worldwide. Pulmonary tissue has extensive capacities to launch injury-responsive repairing programs (IRRPs) to replace the damaged or dead cells upon acute lung injuries. However, the IRRPs are frequently compromised in chronic lung diseases. In this review, we aim to provide an overview of somatic stem cell subpopulations within distal airway epithelium and the underlying mechanisms mediating their self-renewal and trans-differentiation under both physiological and pathological circumstances. We also compared the differences between humans and mice on distal airway structure and stem cell composition. At last, we reviewed the current status and future directions for the development of targeted therapeutics on defective distal airway regeneration and repairment in chronic lung diseases.

Aptamer-modified M cell targeting liposomes for oral delivery of macromolecules.

There is an urgent demand for non-invasive and high compliance delivery systems of macromolecules for long-term therapy. However, oral administration of macromolecules is hindered by low permeability and instability in the gastrointestinal (GI) tract. Therefore, we developed a novel aptamer-modified liposomes (Apt-Lip) with M cell targeting for oral delivery of exenatide (EXT). Firstly, we optimized aptamers to M cells by Cell-SELEX and aptamer truncations. The selected aptamer T-M3 (Apt-T-M3) with high binding affinity (Kd = 176 ± 108 nM) and specificity was modified on the surface of liposomes for targeting M cells. Liposomes were formulated by microfluidics system and characterized in terms of morphology, hydrodynamic diameter, zeta potential, and the efficiency of encapsulation. In comparison with non-targeting liposomes, cell uptake in M cells was significantly enhanced by Apt-Lip. Similarly, the transport efficiency of EXT was 2-fold increase using Apt-Lip in M cells. Additionally, the transepithelial electrical resistance (TEER) of M cell monolayers is significantly reduced. In ex vivo intestinal absorption study, Apt-Lip was proved to possess significantly high intestinal absorption in Peyer's patches (PPs) and M cells-specific targeting capacity. Consequently, Apt-Lip promoted the EXT transport could base not only on M cell mediated transport, but also on enhancement of paracellular permeability. In conclusion, the present study supported Apt-Lip as a promising M cell targeted delivery system for oral delivery of macromolecules.

Impact of urban morphology on the spatial and temporal distribution of PM2.5 concentration: A numerical simulation with WRF/CMAQ model in Wuhan, China.

The urban morphology can significantly change the urban microclimate, which in turn affects the diffusion of air pollutants. Urban planning is the most important means of shaping urban morphology. Therefore, this study takes Wuhan as an example and uses the method of WRF/CMAQ coupled UCM model to analyze the spatial and temporal distribution characteristics of PM2.5 in the Wuhan metropolitan area in winter 2015. The six most important urban morphological indicators in urban planning: the floor area ratio and building height, building density and building width, vegetation coverage ratio, and urban fraction, are selected and classified into three groups. Studying their impact on the spatial and temporal distribution of PM2.5 concentration provides support for urban planners to improve air quality. The results show that the maximum value of PM2.5 concentration in Wuhan urban area occurs in the morning rush hour, and PM2.5 is distributed concentrically in the downtown of the city (within the second ring highway) according to the highways around the city. The PM2.5 concentration in the downtown area with the most extensive urban morphological index is the highest, and it decreases with increasing distance from the downtown. Among the six indicators, building density and urban fraction have the most significant impact on PM2.5 concentration because they have the greatest impact on the wind speed at 10 m. The height of the planetary boundary layer is the key factors affect the vertical and horizontal diffusion of air pollutants. Except for the vegetation coverage ratio, the increase of other urban morphological indicators will lead to a decrease of PM2.5 concentration in Wuhan urban area at night. During the daytime, increasing the floor area ratio and building height will cause an increasing of PM2.5 concentration, but other indicators have the opposite effects.

An Aseptic One-Shot Bottom-Up Method To Produce Progesterone Nanocrystals: Controlled Size and Improved Bioavailability.

Progesterone (PG) is an essential sex hormone with a variety of important biological functions, but its insolubility leads to low bioavailability of most water-based formulations. What is more, the commercial oil-based formulations often cause severe side effects after long-term injection due to poor tissue absorption of oil. Herein, we report an aseptic bottom-up method utilizing emulsion freeze-drying technology that produces size-controllable, highly bioavailable, and water-based PG nanocrystal injection. The key factors that can determine the features of nanocrystals were investigated, including solvents, water-to-oil ratio, drug concentrations, type of surfactants, temperature in freeze-drying process, and lyoprotectants. Mechanisms of crystal growth formation process for PG nanocrystals were also analyzed theoretically. The prepared water-based PG nanocrystal suspension injection (PG/NSI) not only showed quick dissolution behaviors but also had significantly improved bioavailability in vivo. Therefore, this method can effectively control the size of nanocrystals, enhance bioavailability of insoluble drugs, and produce aseptic water-based nanocrystals that can be directly used for injection. Moreover, this method can also be used to prepare nanocrystals with the desired size under aseptic conditions for other poorly water-soluble drugs.

Synthesis and electrical properties of ZnO nanowires.

Vertically aligned ZnO nanowires were synthesized on the p(+) silicon chip by modifying the CVD process with a vapor trapping design. Scanning electron microscopy was used to investigate the morphology of as-obtained nanowires. X-ray diffraction showed that the obtained nanowires were ZnO crystalline. The rectifying characteristics of the p-n heterojunction composed of ZnO nanowires and a p(+) silicon chip were observed. The positive turn-on voltage was 0.5V and the reverse saturation current was 0.01mA. These vertically aligned ZnO nanowires showed a low field emission threshold of 4V/microm at a current density of 0.1microA/cm(2). The dependence of emission current density on the electric field followed Fowler-Nordheim relationship.

Morphology investigation of Ag(TCNQ) synthesized by the vapor-transport reaction method.

Ag(TCNQ) nanostructures with wire-, belt- and flower-like morphologies have been prepared on Si wafers by a vapor-transport reaction between silver and TCNQ without additional catalyst. The morphologies were characterized by SEM and optical microscopy. The composition of nanowires was tested by Raman spectroscopy. The growth mechanism of different morphologies based on the VS mechanism is emphasized.

Scanning electron microscopy investigation of Cu-TCNQ micro/nanostructures synthesized via vapor-induced reaction method.

Micro/nanostructures based on the metal-organic complex Cu-TCNQ were successfully synthesized by a novel method: vapor-induced reaction. Scanning electron microscopy was used to investigate the morphology on the three different parts of the substrate: the hot reaction area, a transitional reaction area and an induced reaction area. The results show that the morphology of the as-grown structures evolves from microstructures to nanostructures. The formation mechanism of these different structures may be understood from electrochemical principles and the decreasing concentration of TCNQ.

Microscopy investigation of Ag-TCNQ micro/nanostructures synthesized via two solution routes.

The micro/nanostructures of metal-organic complex Ag-TCNQ were successfully synthesized by the reaction between Ag film and TCNQ dissolved in acetonitrile via two solution routes, i.e. immerging and dipping reaction. X-ray diffraction confirmed that the obtained Ag-TCNQ micro/nanostructures were crystalline. The morphology of the as-grown structures varied from straight nanowires and microtubes to complex fractals and dendrites. The growth mechanism of the mainly dendrites may be considered within the framework of DLA model.