Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics into the liver. However, a main challenge remains to develop LNP formulations for selective delivery of RNA into certain types of liver cells, such as hepatocytes and liver sinusoidal endothelial cells (LSECs). Here, we report the engineered LNPs for the targeted delivery of RNA into hepatocytes and LSECs. The effects of particle size and polyethylene glycol–lipid content in the LNPs were evaluated for the hepatocyte-specific delivery of mRNA by ApoE-mediated cellular uptake through low-density lipoprotein receptors. Targeted delivery of RNA to LSECs was further investigated using active ligands. Incorporation of mannose allowed the selective delivery of RNA to LSECs, while minimizing the unwanted cellular uptake by hepatocytes. These results demonstrate that engineered LNPs have great potential for the cell type–specific delivery of RNA into the liver and other tissues.

The aim of this study was to characterize scratching behavior elicited by central administration of morphine or bombesin in rats, and to determine the role of opioid receptors in scratching induced by both pruritogenic agents. Central administration included intracisternal (i.c.), intrathecal (i.t.), and intracerebroventricular (i.c.v.) routes. Scratching events made with hind paws were counted by observers blinded to treatment conditions. Intracisternal morphine (0.01-0.1 μg) produced dosedependent increases in scratching; the maximum response to i.c. morphine 0.1 μg was approximately 500 scratches within a 1-hour period. Neither i.t. nor i.c.v. morphine significantly increased scratching. Bombesin (0.01 -0.32 μg) elicited robust scratching following i.c. administration. The maximum response to i.c. bombesin 0.32 μg was approximately 4000 scratches within a 1-hour period. Both i.t. and i.c.v. bombesin produced profound scratching at similar doses. Antagonist studies confirmed that mu-opioid receptors selectively mediate i.c. morphine-induced scratching. However, selective mu-, kappa-, and delta-opioid antagonists did not attenuate i.c. bombesin-induced scratching. These results demonstrate that morphine and bombesin elicit scratching through different receptor mechanisms, at different central sites, and to different degrees.

Patients with poor nutritional status and extensive lung involvement tend to experience deterioration of nodular bronchiectatic MAC lung disease.

No abstract

A time-domain microwave imaging system with improved image quality is presented for early detection of breast cancer. The timedomain system has the advantage of short scan time compared with the frequency-domain system but suffers from low signal-to-noise ratio (SNR) due to high attenuation of the RF signal within the breast tissue. Signal averaging of repeated measurements can improve the SNR, but this method also smears the signal peaks due to the signal-averaged jitter, which adversely affects the reconstructed image quality. An image enhancement method using Gaussian bandpass filtering (BPF) is proposed for a time-domain imaging system. The results from the proposed method were compared with those from the deconvolution method, which is typically used to remove the effects of signal-averaged timing jitter in short pulse measurements. Simulation results with a 3D hemispherical homogeneous breast model containing tumour cells revealed improvement of the reconstructed image quality with the proposed method in the presence of timing jitter. The signal-to-mean ratio was increased from 6.46 to 14.15 with BPF, whereas deconvolution resulted in an increase to 9.36. Simulation results with a non-homogeneous realistic breast model also showed image enhancement with the proposed method.