Y-Chromosome Evidence for Common Ancestry of Three Chinese Populations with a High Risk of Esophageal Cancer

High rates of esophageal cancer (EC) are found in people of the Henan Taihang Mountain, Fujian Minnan, and Chaoshan regions of China. Historical records describe great waves of populations migrating from north-central China (the Henan and Shanxi Hans) through coastal Fujian Province to the Chaoshan plain. Although these regions are geographically distant, we hypothesized that EC high-risk populations in these three areas could share a common ancestry. Accordingly, we used 16 East Asian-specific Y-chromosome biallelic markers (single nucleotide polymorphisms; Y-SNPs) and six Y-chromosome short tandem repeat (Y-STR) loci to infer the origin of the EC high-risk Chaoshan population (CSP) and the genetic relationship between the CSP and the EC high-risk Henan Taihang Mountain population (HTMP) and Fujian population (FJP). The predominant haplogroups in these three populations are O3*, O3e*, and O3e1, with no significant difference between the populations in the frequency of these genotypes. Frequency distribution and principal component analysis revealed that the CSP is closely related to the HTMP and FJP, even though the former is geographically nearer to other populations (Guangfu and Hakka clans). The FJP is between the CSP and HTMP in the principal component plot. The CSP, FJP and HTMP are more closely related to Chinese Hans than to minorities, except Manchu Chinese, and are descendants of Sino-Tibetans, not Baiyues. Correlation analysis, hierarchical clustering analysis, and phylogenetic analysis (neighbor-joining tree) all support close genetic relatedness among the CSP, FJP and HTMP. The network for haplogroup O3 (including O3*, O3e* and O3e1) showed that the HTMP have highest STR haplotype diversity, suggesting that the HTMP may be a progenitor population for the CSP and FJP. These findings support the potentially important role of shared ancestry in understanding more about the genetic susceptibility in EC etiology in high-risk populations and have implications for determining the molecular basis of this disease

Adaptation in multisensory neurons: Impact on cross-modal enhancement

Adaptation is a ubiquitous property of sensory neurons. Multisensory neurons, receiving convergent input from different sensory modalities, also likely exhibit adaptation. The responses of multisensory superior colliculus neurons have been extensively studied, but the impact of adaptation on these responses has not been examined. Multisensory neurons in the superior colliculus exhibit cross-modal enhancement, an often non-linear and nonadditive increase in response when a stimulus in one modality is paired with a stimulus in a different modality. We examine the possible impact of adaptation on cross-modal enhancement within the framework of a simple model of adaptation for a neuron employing a saturating, logistic response function. We consider how adaptation to an input's mean and standard deviation affects cross-modal enhancement, and also how the statistical correlations between two different modalities influence cross-modal enhancement. We determine the optimal bimodal stimuli to present a bimodal neuron that evoke the largest changes in cross-modal enhancement under adaptation to input statistics. The model requires separate gains for each modality, unless the statistics specific to each modality have been standardised by prior adaptation in earlier, unisensory neurons. The model also predicts that increasing the correlation coefficient between two modalities reduces a multisensory neuron's overall gain

STUDIES ON WASTE-WATER TREATMENT BY MEANS OF INTEGRATED BIOLOGICAL POND SYSTEM - DESIGN AND FUNCTION OF MACROPHYTES

A biological treatment pond system to purify municipal wastewater from a medium-sized city has been operated for 3 years and gained good results. Macrophytes took a very important part in this system. The macrophyte ponds and zones were designed spacially and periodically different to test their purification efficiencies.The purifing system was divided into three functional zones: purifing zone, effluent upgrading zone and multi-utilization zone. Macrophytes were planted in several subzones in series in some ponds. The experiments showed that the multi-macrophyte zone system revealed greater purification efficiencies than those of traditional oxidation ponds as well as general macrophyte ponds. The system reached high reductions of COD, BOD, TSS, TN and TP. The activity of mutagenic agents and numbers of virus and bacteria were significantly decreased during the process of purification. The effluent from the system was greatly upgraded and could be used in fishery and agriculture. The harvested macrophytes from the purifing zone and effluent upgrading zone could be put into the multi-utilization zone as feed, fertilizer, biogas, etc. The idea of resourcization of wastewater was being put into practice. The studies also showed that some macrophytes revealed strong ability to inhibit algae growth not because of light, nutrient and space competition. These results had been used in the treatment system design and gained expected effects. Plant harvesting did not yield dramatic effects on reductions of the main pollutants, though it did affect remarkably the biomass productivity of the macrophytes

Annonaceous acetogenins nanosuspensions stabilized by PCL–PEG block polymer: significantly improved antitumor efficacy

Jingyi Hong,1,* Yanhong Li,1,2,* Yijing Li,1 Yao Xiao,1,2 Haixue Kuang,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 2School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China *These authors contributed equally to this work Abstract: Annonaceous acetogenins (ACGs) have shown superior antitumor activity against a variety of cancer cell lines, but their clinical application has been limited by their poor solubility. In this study, ACGs-nanosuspensions (NSps) were successfully prepared by a precipitation ultrasonic method using monomethoxypoly (ethylene glycol)2000–poly (ε-caprolactone)2000 (mPEG2000–PCL2000) as a stabilizer. The resultant ACGs-NSps had a mean particle size of 123.2 nm, a zeta potential of -20.17 mV, and a high drug payload of 73.68%. ACGs-NSps were quite stable in various physiological solutions, and they exhibited sustained drug release. Compared to free drug, ACGs-NSps exhibited stronger cytotoxicity against 4T1, MCF-7, and HeLa cells. An in vivo real-time biodistribution investigation after labeling with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, a noninvasive near-infrared fluorescence probe, demonstrated that ACGs-NSps could effectively accumulate in tumor. An in vivo antitumor activity study in 4T1 tumor-bearing mice revealed that ACGs-NSps achieved much better therapeutic efficacy than the traditional dosage form (oil solution) even at 1/10 of the dose (74.83% vs 45.53%, P<0.05), demonstrating that NSp was a good dosage form for ACGs to treat cancer. Keywords: annonaceous acetogenins, mPEG2000–PCL2000, near–infrared fluorescence, biodistribution, antitumor efficac

A stabilizer-free and organic solvent-free method to prepare 10-hydroxycamptothecin nanocrystals: in vitro and in vivo evaluation

Xiaofeng Yang,1 Yingying Liu,1,2 Yanna Zhao,1 Meihua Han,1 Yifei Guo,1 Haixue Kuang,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of China Abstract: 10-Hydroxycamptothecin (10-HCPT) is a promising anticancer drug with a wide spectrum of antitumor activities. Due to its poor solubility, the carboxylate form that shows high water solubility but minimal anticancer activity and pharmacokinetic defects is used in the marketed 10-HCPT injections, resulting in its limited clinical application. To develop a simple, safe, and highly effective drug delivery system, a modified acid–base microprecipitation combined with a high-pressure homogenization technique was adopted to prepare 10-HCPT nanocrystals. Neither organic solvents nor stabilizers were employed throughout the preparation process. The in vitro and in vivo performances of the resulting10-HCPT nanocrystals were investigated systematically. The nanocrystals were spherical with a small size of ~130 nm, and the actual drug-loading content was as high as 75%. The nanocrystals displayed a sustained release pattern and were proven to have a higher cell uptake and antiproliferative activity than the 10-HCPT injections. The 10-HCPT nanocrystals also showed enhanced drug accumulation in tumors and better anticancer efficacy in 4T1-bearing mice. In summary, the 10-HCPT nanocrystals prepared in this study seem to be a promising delivery system for a new form of 10-HCPT dosages. Keywords: 10-hydroxycamptothecin, drug delivery, poloxamer 188, high drug payload, 4T1 cell

STUDIES ON WASTE-WATER TREATMENT BY MEANS OF INTEGRATED BIOLOGICAL POND SYSTEM - DESIGN AND FUNCTION OF MACROPHYTES

A biological treatment pond system to purify municipal wastewater from a medium-sized city has been operated for 3 years and gained good results. Macrophytes took a very important part in this system. The macrophyte ponds and zones were designed spacially and periodically different to test their purification efficiencies.The purifing system was divided into three functional zones: purifing zone, effluent upgrading zone and multi-utilization zone. Macrophytes were planted in several subzones in series in some ponds. The experiments showed that the multi-macrophyte zone system revealed greater purification efficiencies than those of traditional oxidation ponds as well as general macrophyte ponds. The system reached high reductions of COD, BOD, TSS, TN and TP. The activity of mutagenic agents and numbers of virus and bacteria were significantly decreased during the process of purification. The effluent from the system was greatly upgraded and could be used in fishery and agriculture. The harvested macrophytes from the purifing zone and effluent upgrading zone could be put into the multi-utilization zone as feed, fertilizer, biogas, etc. The idea of resourcization of wastewater was being put into practice. The studies also showed that some macrophytes revealed strong ability to inhibit algae growth not because of light, nutrient and space competition. These results had been used in the treatment system design and gained expected effects. Plant harvesting did not yield dramatic effects on reductions of the main pollutants, though it did affect remarkably the biomass productivity of the macrophytes

Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes.

BACKGROUND: The highly genetically diverse HIV-1 group M subtypes may differ in their biological properties. Nef is an important mediator of viral pathogenicity; however, to date, a comprehensive inter-subtype comparison of Nef in vitro function has not been undertaken. Here, we investigate two of Nef's most well-characterized activities, CD4 and HLA class I downregulation, for clones obtained from 360 chronic patients infected with HIV-1 subtypes A, B, C or D. RESULTS: Single HIV-1 plasma RNA Nef clones were obtained from N=360 antiretroviral-naïve, chronically infected patients from Africa and North America: 96 (subtype A), 93 (B), 85 (C), and 86 (D). Nef clones were expressed by transfection in an immortalized CD4+ T-cell line. CD4 and HLA class I surface levels were assessed by flow cytometry. Nef expression was verified by Western blot. Subset analyses and multivariable linear regression were used to adjust for differences in age, sex and clinical parameters between cohorts. Consensus HIV-1 subtype B and C Nef sequences were synthesized and functionally assessed. Exploratory sequence analyses were performed to identify potential genotypic correlates of Nef function. Subtype B Nef clones displayed marginally greater CD4 downregulation activity (p = 0.03) and markedly greater HLA class I downregulation activity (p < 0.0001) than clones from other subtypes. Subtype C Nefs displayed the lowest in vitro functionality. Inter-subtype differences in HLA class I downregulation remained statistically significant after controlling for differences in age, sex, and clinical parameters (p < 0.0001). The synthesized consensus subtype B Nef showed higher activities compared to consensus C Nef, which was most pronounced in cells expressing lower protein levels. Nef clones exhibited substantial inter-subtype diversity: cohort consensus residues differed at 25% of codons, while a similar proportion of codons exhibited substantial inter-subtype differences in major variant frequency. These amino acids, along with others identified in intra-subtype analyses, represent candidates for mediating inter-subtype differences in Nef function. CONCLUSIONS: Results support a functional hierarchy of subtype B > A/D > C for Nef-mediated CD4 and HLA class I downregulation. The mechanisms underlying these differences and their relevance to HIV-1 pathogenicity merit further investigation