A WOX homolog disrupted by a transposon led to the loss of spines and contributed to the domestication of lettuce.

The loss of spines is one of the most important domestication traits for lettuce (Lactuca sativa). However, the genetics and regulation of spine development in lettuce remain unclear. We examined the genetics of spines in lettuce using a segregating population derived from a cross between cultivated and wild lettuce (Lactuca serriola). A gene encoding WUSCHEL-related homeobox transcription factor, named as WOX-SPINE1 (WS1), was identified as the candidate gene controlling the spine development in lettuce, and its function on spines was verified. A CACTA transposon was found to be inserted into the first exon of the ws1 allele, knocking out its function and leading to the lack of spines in cultivated lettuce. All lettuce cultivars investigated have the nonfunctional ws1 gene, and a selection sweep was found at the WS1 locus, suggesting its important role in lettuce domestication. The expression levels of WS1 were associated with the density of spines among different accessions of wild lettuce. At least two independent loss-of-function mutations in the ws1 gene caused the loss of spines in wild lettuce. These findings provide new insights into the development of spines and facilitate the exploitation of wild genetic resources in future lettuce breeding programs.

Shunaoxin dropping pill improves cognitive functions of rats with chronic cerebral hypoperfusion via the microbiota-gut-brain axis.

Chronic cerebral hypoperfusion (CCH) is a major risk factor for cognitive decline and degenerative processes. Shunaoxin dropping pill (SNX) has been clinically used to treat cerebrovascular diseases. However, the effect and mechanism of SNX in treating CCH-induced cognitive impairment remain unclear. In this study, CCH was induced in rats using permanent bilateral common carotid artery ligation (2-VO). CCH rats were characterized by impaired spatial learning and memory ability, as well as increased oxidative stress and inflammation in the hippocampus. Additionally, CCH rats had reduced richness and biodiversity of fecal microbiota, which showed a strong correlation with altered serum metabolites. SNX significantly improved the cognitive impairment and restored the dysbiosis of fecal microbiota and serum metabolites in CCH rats. Notably, SNX did not prevent cognitive impairment in antibiotics-treated CCH rats. Our findings suggest that the microbiota-gut-brain axis is a promising therapeutic target for the treatment of CCH-induced cognitive impairment.

Whole-genome resequencing of 445 Lactuca accessions reveals the domestication history of cultivated lettuce.

Lettuce (Lactuca sativa) is an important vegetable crop worldwide. Cultivated lettuce is believed to be domesticated from L. serriola; however, its origins and domestication history remain to be elucidated. Here, we sequenced a total of 445 Lactuca accessions, including major lettuce crop types and wild relative species, and generated a comprehensive map of lettuce genome variations. In-depth analyses of population structure and demography revealed that lettuce was first domesticated near the Caucasus, which was marked by loss of seed shattering. We also identified the genetic architecture of other domestication traits and wild introgressions in major resistance clusters in the lettuce genome. This study provides valuable genomic resources for crop breeding and sheds light on the domestication history of cultivated lettuce.

Anionic LPD complexes for gene delivery to macrophage: preparation, characterization and transfection in vitro.

In the present study, anionic lipid/peptide/DNA (LPD) complexes consisting of pH-sensitive liposome and protamine were introduced as the carriers targeting RAW 264.7 cell line, which had been reported to be difficult for transfection. The LPD complexes were physically characterized. The pH sensitivities and sizes of liposomes were investigated. The zeta potentials of LPD complexes altered significantly with the addition of protamine sulfate and anionic liposomes. It was demonstrated that the carriers produced an increase in the stability of plasmid DNA against DNase I. The TEM showed that the size distribution of LPD complexes was irregular. In the in vitro transfection, the efficiency of LPD complexes was higher than that of Lipofectamine 2000 and protamine/DNA complexes, but lower than that of electroporation. A possible mechanism for the internalization of plasmid DNA mediated by the anionic LPD complexes was also proposed. With a high safety certificated by MTT assay, LPD complexes prepared in this study might be potentially employed as a macrophage gene therapy.

Investigations of a novel self-emulsifying osmotic pump tablet containing carvedilol.

Carvedilol has been made into a novel osmotic pump tablet which includes Gelucire 44/14, Lutrol F68, Transcutol P, silicon dioxide, mannitol, citric acid, and sodium hydrogen carbonate. The Self-emulsifying osmotic pump tablet (SEOPT) has two outstanding features. It could improve the bioavailability of carvedilol by self-emulsifying drug delivery system (SEDDS), control the release rate and make the plasma concentrations more stable by elementary osmotic pump tablet. The results of transmission electron microscope (TEM) and particle size assessment showed that the shape of the resultant emulsion was round and regular, the average diameter of the particles was 246 nm. Since the solubility of carvedilol was improved by the emulsion, the elementary SEOPT could guarantee a complete release of carvedilol under the osmotic pressure of mannitol. The cumulative release at 12 hr was 85.18%. Therefore the disadvantage that lipophilic drugs can not be released completely when prepared into elementary osmotic pump tablet was resolved. The results of Differential scanning calorimetry (DSC), Infrared spectroscopy (IR) and X-ray diffraction diffraction (XRD) proved that carvedilol was amorphous in the preparation. The relative bioavailability of carvedilol in beagle dogs was 156.78%. The plasma concentrations were more stable compared with that of commercially available tablet (Luode). And the in vitro and in vivo correlation was good (r = 0.9725). Therefore, the elementary SEOPT developed in this paper might provide a new idea for preparing lipophilic drugs into osmotic pump tablet conveniently.

Preparation and evaluation of SEDDS and SMEDDS containing carvedilol.

A new self-emulsifying drug delivery system (SEDDS) and self-microemulsifying drug delivery system (SMEDDS) have been developed to increase the solubility, dissolution rate, and, ultimately, oral bioavailability of a poorly water soluble drug, carvedilol. Ternary phase diagrams were used to evaluate the self-emulsification and self-microemulsfication domains. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The minimum self-emulsification time was found at a Tween 80 content of 40%. The particle size distribution and zeta-potential were determined. Benzoic acid had a dual function, it improved the self-emulsification performance of SEDDS and SMEDDS in 0.1 N HCl and lead to a positively charged emulsion. The in vitro dissolution rate of carvedilol from SEDDS and SMEDDS was more than two-fold faster compared with that from tablets. The developed SEDDS formulations significantly improved the oral bioavailability of carvedilol significantly, and the relative oral bioavailability of SEDDS compared with commercially available tablets was 413%.