Design, synthesis and biological evaluation of novel amide-linked 18ß-glycyrrhetinic acid derivatives as novel ALK inhibitors.

A series of novel amide-linked 18ß-glycyrrhetinic acid derivatives were developed by incorporating substituted piperazine amide fragments into the C30-COOH of 18ß-glycyrrhetinic acid scaffold. The synthesized compounds were evaluated for their anticancer activity against Karpas299, A549, HepG2, MCF-7, and PC-3 cell lines by MTT assay. Besides, some compounds with electron-withdrawing groups on phenyl moieties exhibited noticeable antiproliferative activity. The most potent compound 4a was also found to be non-toxic to normal human hepatocytes LO2 cells. The compound 4a exhibited moderate inhibitory activity against wild-type ALK with an IC50 value of 203.56 nM and relatively weak potent activity to c-Met (IC50 > 1000 nM). Molecular docking studies were performed to explore the diversification in bonding patterns between the compound 4a and Crizotinib.

Liuwei Dihuang Pill () Treats Postmenopausal Osteoporosis with Shen (Kidney) Yin Deficiency via Janus Kinase/Signal Transducer and Activator of Transcription Signal Pathway by Up-regulating Cardiotrophin-Like Cytokine Factor 1 Expression.

OBJECTIVES: To investigate the mechanism of Liuwei Dihuang Pill (, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency. METHODS: In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. RESULTS: The mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3. CONCLUSIONS: The CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.

A data compression algorithm for wireless sensor networks based on an optimal order estimation model and distributed coding.

In many wireless sensor network applications, the possibility of exceptions occurring is relatively small, so in a normal situation, data obtained at sequential time points by the same node are time correlated, while, spatial correlation may exist in data obtained at the same time by adjacent nodes. A great deal of node energy will be wasted if data which include time and space correlation is transmitted. Therefore, this paper proposes a data compression algorithm for wireless sensor networks based on optimal order estimation and distributed coding. Sinks can obtain correlation parameters based on optimal order estimation by exploring time and space redundancy included in data which is obtained by sensors. Then the sink restores all data based on time and space correlation parameters and only a little necessary data needs to be transmitted by nodes. Because of the decrease of redundancy, the average energy cost per node will be reduced and the life of the wireless sensor network will obviously be extended as a result.

[The mixed major gene plus polygenes inheritance for female fertility in wheat (Triticum aestivum L.)].

Three sets of data for the P1, P2, F1, and F2 populations derived from three crosses between the normal fertility wheat (Triticum aestivum L.) cultivars with different ecotypes and the female sterile line (XND126) were used to investigate the inheritance of female fertility in wheat using mixed major gene plus polygenes inheritance model in 2005 and 2006. The results from the joint segregation analysis of the four generations showed that female fertility in wheat is controlled by two major genes plus polygenes, and the interaction between the two major genes is also detected.