Synthesis of Diastereoenriched Oxazolo[5,4-b]indoles via Catalyst-Free Multicomponent Bicyclizations.

A new and highly eco-friendly approach to diverse and functionalized oxazolo[5,4-b]indoles with good yield and high diastereoselectivity (up to >99:1) has been disclosed from simple and readily available arylglyoxals with cyclic enaminones and amino acids. These microwave-assisted transformations in environmentally compatible ethanol resulted in continuous multiple bond-forming events including C-C, C-N, and C-O bonds, enabling catalyst-free multicomponent bicyclizations to rapidly build up functional N,O-heterocycles.

[Novel liposomal drug delivery system actively targeting Cryptococcus neoformans and elimination of infection].

The purpose of this study is to develop a liposomal drug delivery system actively targeting Cryptococcus neoformans and explore its feasibility in therapy of cryptococcal infection. The specific fungi-binding peptide was screened from 12-mer random phage display library, and linked to PEG-DSPE as the functional material of liposomes. The targeting capability of peptide-modified liposomes were investigated by fungi binding assay in vitro and fluorescence imaging in vivo. Itraconazole as a model drug were then encapsulated in the liposomes and were evaluated in pharmacodynamic test in vitro and for therapeutic effects against cryptococcal meningitis complicated with pulmonary cryptococcosis in vivo. The results showed that the peptide (sequence: NNHREPPDHRTS) could selectively recognize Cryptococcus and effectively mediate the corresponding liposomal formulation to accumulate in the infection site in vivo. This peptide-modified liposome has a small particle size (mean diameter of 88.25 ± 2.43 nm) with a homogeneous distribution and high encapsulation efficiency (88.05 ± 0.25 %) of itraconazole. After intravenous administration, the pathogens were obviously eliminated in lung and brain, and the life-span of model mice were significantly prolonged, suggesting a promising potential of this cryptococcosis targeting strategy.

Contralateral S1 nerve root transfer for motor function recovery in the lower extremity among patients with central nervous system injury: study protocol for a randomized controlled trial.

BACKGROUND: Central nervous system injury (CNSI) comprises a series of common diseases that severely affect patients' motor function and quality of life and is associated with high disability and mortality rates. Previous studies have shown that contralateral lumbosacral nerve root transfer significantly improved the function of the paralyzed limb in rat models of CNSI. These studies showed that severing the sacral 1 nerve root (S1) did not damage the function of the ipsilateral lower extremity. Thus, we speculate that contralateral S1 nerve root transfer can improve the recovery of a paralyzed limb. Because no associated rigorously designed randomized controlled trial has evaluated the effectiveness of contralateral S1 nerve transfer thus far, we designed this clinical trial to compare the effects of this new treatment approach with those of traditional treatments in paralyzed patients after chronic CNSI. METHODS: This is a single-center, prospective, randomized controlled trial. Forty patients, who meet the inclusion criteria and have hemiplegia caused by chronic CNSI, will be randomly divided into the surgical or non-surgical group. The treatment effect in the 2 groups will be assessed before and 3, 6, 9, 12, 18, and 24 months after intervention by using numerous scales and resting-state functional magnetic resonance imaging. The primary outcome will be the Fugl-Meyer score for the lower limbs 24 months after treatment. The secondary outcomes include the modified Ashworth spasm scale, the modified Barthel scale, 10-m walking speed measurement results, three-dimensional gait analysis, muscle strength testing, electromyography, and resting-state functional magnetic resonance imaging findings. Safety outcomes and adverse events will be observed simultaneously. DISCUSSION: We expect that the surgery will improve the sensorimotor functions of the paralyzed limb, and the results of this trial will provide high-quality clinical evidence for a new efficient treatment strategy for disability after CNSI. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014414, registration date: 12 January 2018.

Sparks fly between ascorbic acid and iron-based nanozymes: A study on Prussian blue nanoparticles.

Herein we reported Prussian blue nanoparticles (PBNPs) possess ascorbic acid oxidase (AAO)- and ascorbic acid peroxidase (APOD)-like activities, which suppressed the formation of harmful H2O2 and finally inhibited the anti-cancer efficiency of ascorbic acid (AA). This newly revealed correlation between iron and AA could provide new insight for the studies of nanozymes and free radical biology.