Identification of a diverse synthetic abietane diterpenoid library and insight into the structure-activity relationships for antibacterial activity

A diverse natural product-like (NPL) synthetic abietane diterpenoid library containing 86 compounds were obtained and the SARs were studied based on their antibacterial potential. Further in vitro cytotoxic and in silico drug-like properties evaluation showed that the potent antibacterial compound 84 had good drug-like properties and displayed low cytotoxicity toward noncancerous mammalian cells, indicating the study of AA and DHAA might be a good starting point for the search of novel antimicrobial molecules. Future work should be focused on the optimization of their potency and selectivity.     

Discovery of aminocyclohexene analogues as selective and orally bioavailable hNav1.7 inhibitors for analgesia

hNav1.7 receives a lot of attention owing to its attractive mechanism of action in pain processing pathway. We have previously reported our design of a novel series of tetrahydropyridine analogues towards hNav1.7 selective inhibitors. Herein, we disclose further efforts to the optimization of hit compound (?)-6, which led to the identification of aminocyclohexene analogues (?)-9 and (?)-17 with good potency, high selectivity, and minimal CYP inhibition. Both compounds (?)-9 and (?)-17 demonstrated improved pharmacokinetic profiles in rats, and robust efficacy in rat formalin-induced nociception and spinal nerve ligation (SNL) models.     

Genome-Wide Discovery of DNA Polymorphisms in Mei (<Emphasis Type="Italic">Prunus mume</Emphasis> Sieb. et Zucc.), an Ornamental Woody Plant,with Contrasting Tree Architecture and their Functional Relevance for Weeping Trait

Next-generation sequencing technologies provide opportunities to ascertain the genetic basis of phenotypic differences, even in the closely related cultivars via detection of large amount of DNA polymorphisms. In this study, we performed whole-genome re-sequencing of two mei cultivars with contrasting tree architecture. 75.87 million 100 bp pair-end reads were generated, with 92 % coverage of the genome. Re-sequencing data of two former upright mei cultivars were applied for detecting DNA polymorphisms, since we were more interested in variations conferring weeping trait. Applying stringent parameters, 157,317 mutual single nucleotide polymorphisms (SNPs) and 15,064 mutual insertions-deletions (InDels) were detected and found unevenly distributed within and among the mei chromosomes, which lead to the discovery of 220 high-density, 463 low-density SNP regions together with 80 high-density InDel regions. Additionally, 322 large-effect SNPs and 433 large-effect InDels were detected, and 10.09 % of the SNPs were observed in coding regions. 5.25 % SNPs in coding regions resulted in non-synonymous changes. Ninety SNPs were chosen randomly for validation using high-resolution melt analysis. 93.3 % of the candidate SNPs contained the predicted SNPs. Pfam analysis was further conducted to better understand SNP effects on gene functions. DNA polymorphisms of two known QTL loci conferring weeping trait and their functional effect were also analyzed thoroughly. This study highlights promising functional markers for molecular breeding and a whole-genome genetic basis of weeping trait in mei.     

Silencing of a lipase maturation factor 2‐like gene by wheat‐mediated RNAi reduces the survivability and reproductive capacity of the grain aphid,Sitobion avenae

Lipase maturation factor (LMF) family proteins are required for the maturation and transport of active lipoprotein lipases. However, the specific roles of LMF2 remain unknown. In this study, a grain aphid lmf2‐like gene fragment was cloned and was highly similar in sequence to a homologous gene in the pea aphid, Acyrthosiphon pisum. An RNAi vector was constructed with this fragment and used for wheat transformation. The expression of the lmf2‐like gene in aphid, as well as the growth and reproduction of the aphids, was analyzed after feeding on the transgenic wheat. There were no significant differences in the expression of the lmf2‐like gene over development. The expression of the lmf2‐like gene was significantly reduced by 27.6% on the fifth day, and 57.6% on the 10th day after feeding. The total number of aphids produced on the transgenic plants was less than the number produced on control plants, and the difference became significant or after 2 weeks. The molting numbers were also reduced in the aphids reared on the transgenic plants. Our findings indicate that lmf2‐like genes may have potential as a target gene for the control of grain aphids and show that feeding aphids with wheat expressing lmf2‐like RNAi resulted in significant reductions in survival and reproduction.     

Polymorphism of rs3737597 in DISC1 Gene on Chromosome 1q42.2 in sALS Patients: a Chinese Han Population Case-Control Study

Although lots of genes have been revealed to relate to sporadic amyotrophic lateral sclerosis (sALS), its genetic mechanisms still need to be further explored. We aimed to search the novel genetic factors of sALS and assess their contribution. We constructed an integrative dataset based on the 3227 subsignificant genes (P value?<?0.01) from two sALS-related genome-wide association studies (GWAS) (the US and Irish studies). A significant replication between both studies was confirmed by the gene set enrichment analysis in the integral level (P value?<?10^?4). Using the pathway overrepresentation analysis, we revealed the 34 shared Gene Ontology (GO) biological processes from the two independent studies (P value?<?0.01). Among these pathways, the nervous system developmental pathway (NSD function, GO:0007399) was further supported by the previously reported genes related to sALS (P value?=?3.28e?12). Importantly, four of 17 NSD-function-related target genes (disrupted-in-schizophrenia-1 (DISC1), CNTN4, NRXN3, and ERBB4) presented a considerable association with sALS in both studies. To further verify the association between the NSD function target genes and sALS, we preformed a two-stage case–control study based on 500 sALS patients and 500 controls of Chinese Han populations from mainland. A polymorphism of rs3737597 in DISC1 gene involved in the nervous system developmental pathway was closely associated with sALS. The nervous system developmental pathway is a potential pathogenesis of sALS, among them, the polymorphism of rs3737597 in DISC1 might play some roles.     

High altitude flights by ruddy shelduck Tadorna ferruginea during trans‐Himalayan migrations

Birds that migrate across high altitude mountain ranges are faced with the challenge of maintaining vigorous exercise in environments with limited oxygen. Ruddy shelducks are known to use wintering grounds south of the Tibetan Plateau at sea level and breeding grounds north of Himalayan mountain range. Therefore, it is likely these shelducks are preforming high altitude migrations. In this study we analyse satellite telemetry data collected from 15 ruddy shelduck from two populations wintering south of the Tibetan Plateau from 2007 to 2011. During north and south migrations ruddy shelduck travelled 1481 km (range 548–2671 km) and 1238 km (range 548–2689 km) respectively. We find mean maximum altitudes of birds in flight reached 5590 m (range of means 4755–6800 m) and mean maximum climb rates of 0.45 m s^–1 (range 0.23–0.74 m s^–1). The ruddy shelduck is therefore an extreme high altitude migrant that has likely evolved a range of physiological adaptations in order to complete their migrations.     

Optimized ultra-high-pressure-assisted extraction of procyanidins from lychee pericarp improves the antioxidant activity of extracts

To establish optimal ultra-high-pressure (UHP)-assisted extraction conditions for procyanidins from lychee pericarp, a response surface analysis method with four factors and three levels was adopted. The optimum conditions were as follows: 295 MPa pressure, 13 min pressure holding time, 16.0 mL/g liquid-to-solid ratio, and 70% ethanol concentration. Compared with conventional ethanol extraction and ultrasonic-assisted extraction methods, the yields of the total procyanidins, flavonoids, and phenolics extracted using the UHP process were significantly increased; consequently, the oxygen radical absorbance capacity and cellular antioxidant activity of UHP-assisted lychee pericarp extracts were substantially enhanced. LC-MS/MS and high-performance liquid chromatography quantification results for individual phenolic compounds revealed that the yield of procyanidin compounds, including epicatechin, procyanidin A2, and procyanidin B2, from lychee pericarp could be significantly improved by the UHP-assisted extraction process. This UHP-assisted extraction process is thus a practical method for the extraction of procyanidins from lychee pericarp.