Discovery of novel peptide-dehydroepiandrosterone hybrids inducing endoplasmic reticulum stress with effective in vitro and in vivo anti-melanoma activities.

Steroid hybrids have emerged as a type of advantageous compound as they could offer improved pharmacological and pharmaceutical properties. Here, we report a series of novel peptide-dehydroepiandrosterone hybrids, which would effectively induce endoplasmic reticulum stress (ERS) and lead to apoptosis with outstanding in vitro and in vivo anti-melanoma effects. The lead compound IId among various steroids conjugated with peptides and pyridines showed effective in vivo activity in B16 xenograft mice: in medium- and high-dose treatment groups (60 and 80 mg/kg), compound IId would significantly inhibit the growth of tumours by 98%-99% compared to the control group, with the highest survival rate as well. Further mechanism studies showed that compound IId would damage the endoplasmic reticulum and upregulate the ERS markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), which could further regulate caspase and Bcl-2 family proteins and lead to cell apoptosis. The compound IId was also proven to be effective in inhibiting B16 cell migration and invasion.

The Effectiveness and Cost-effectiveness of a Parenting Intervention Integrated with Primary Health Care on Early Childhood Development: a Cluster-Randomized Controlled Trial.

Developing countries require interventions that can sustainably improve early childhood development (ECD) at scale because hundreds of millions of children are at risk of poor development. This study examined the effectiveness and cost-effectiveness of a parenting intervention integrated with primary health care in terms of ECD. A cluster-randomized controlled trial was conducted in 20 urban communities in China, with 82 and 86 children aged 1-2 months enrolled in the intervention and control groups, respectively, and 71 and 69 children, respectively, followed to 14 months of age. All children in both groups received routine primary health care services. Intervention caregivers received a parenting pamphlet and two parenting training sessions during well-child clinic visits; those with children with suspected developmental delay received additional parenting guidance by telephone. Compared with controls, children receiving the intervention had similar developmental outcomes, measured with the Chinese version of the Ages & Stages Questionnaires third edition (ASQ-C), at baseline, but had significantly higher communication (adjusted mean difference = 0.26; 95% CI 0.03, 0.51), fine motor (adjusted mean difference = 0.19; 95% CI 0.01, 0.37), and overall (adjusted mean difference = 0.25; 95% CI 0.10, 0.41) ASQ-C z-scores after 12 months of the intervention. The intervention cost per child was $50.87, and the costs for increasing the communication, fine motor, and overall ASQ-C scores by one SD were $195.65, $267.74, and $203.48, respectively. Our findings indicate that the integration of a parenting intervention with existing primary health care is a cost-effective way to improve ECD.

Application of molecularly imprinted polymers for the analysis of polycyclic aromatic hydrocarbons in lipid matrix-based biological samples.

High-accuracy analyses of polycyclic aromatic hydrocarbons (PAHs) in lipid matrix-based biological samples are highly necessary. We investigated the cleanup performance of the commercially available molecularly imprinted polymers (MIPs) to analyze PAHs in various biological samples (i.e., butter, peanut oil, pork belly, and human umbilical cord), and compared this method with the commonly used gel permeation chromatography (GPC). After primary cleanup with a MIP or GPC column, the extracts were further cleaned with a neutral aluminum oxide column. Then, we measured 16 PAH congeners using gas chromatography-mass spectrometry. The MIP method allowed PAH recovery levels as high as those measured with the GPC method to be obtained. More than 95% of the crude fats of butter, peanut oil, and pork belly were removed, although only ~ 50% were removed for human umbilical cord. The scan-mode ion chromatograms of the final extracts cleaned with the MIP method had responses similar to solvent blank for the four types of samples, which were slightly better than those cleaned with GPC. Moreover, the PAH concentrations in the MIP operation blank were generally lower than those of GPC operation blanks. These results indicated that MIP could be applied to the analysis of PAHs in various lipid matrix-based biological samples. Graphical abstract The schematic diagram of a molecularly imprinted polymer column and the elution curves of polycyclic aromatic hydrocarbons and crude fats of various biological samples.

Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice.

Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China.

An infant and child feeding index is associated with child nutritional status in rural China.

BACKGROUND: Some researchers have developed child feeding indices to summarize child feeding practices so that they can compare child feeding practices across countries and monitor changes over time within a given country. AIMS: An adapted version of the infant and child feeding index (ICFI) developed by Ruel and Menon was used to examine its association with nutritional status of infants living in a rural community in China. METHODS: A cross-sectional survey of 501 children aged 6-11 mo was conducted with their mothers in 8 townships between May 2006 and March 2007. ICFI was developed based on 24-h dietary recall and food frequency information. The associations between ICFI and anthropometric indices including length-for-age (LAZ), weight-for-age (WAZ), and weight-for-length (WLZ) Z-scores were examined separately. General linear regression models were used to adjust for potential confounders including the children's, parents' and households' sociodemographic characteristics. RESULTS: The ICFI was associated with both WAZ (adjusted WAZ means: 0.39, 0.47, and 0.54 for the 1st, 2nd, and 3rd tercile, respectively, P<0.05) and WLZ (adjusted WLZ means: 0.47, 0.74, and 0.79 for the 1st, 2nd, and 3rd tercile, respectively, P<0.05). But it was not associated with children's LAZ. Among the components of ICFI, dietary diversity, meal frequency and bottlefeeding were positively associated with the children's anthropometric indices. CONCLUSIONS: ICFI and its components could be used to assess effect of complementary feeding practices on child growth.