Circulating tumor DNA profiling reveals clonal evolution and real-time disease progression in advanced hepatocellular carcinoma.

Circulating tumor DNA (ctDNA) provides a potential non-invasive biomarker for cancer diagnosis and prognosis, but whether it could reflect tumor heterogeneity and monitor therapeutic responses in hepatocellular carcinoma (HCC) is unclear. Focusing on 574 cancer genes known to harbor actionable mutations, we identified the mutation repertoire of HCC tissues, and monitored the corresponding ctDNA features in blood samples to evaluate its clinical significance. Analysis of 3 HCC patients' mutation profiles revealed that ctDNA could overcome tumor heterogeneity and provide information of tumor burden and prognosis. Further analysis was conducted on the 4th HCC case with multiple lesion samples and sequential plasma samples. We identified 160 subclonal SNVs in tumor tissues as well as matched peritumor tissues with PBMC as control. 96.9% of this patient's tissue mutations could be also detected in plasma samples. These subclonal SNVs were grouped into 9 clusters according to their trends of cellular prevalence shift in tumor tissues. Two clusters constituted of tumor stem somatic mutations showed circulating levels relating with cancer progression. Analysis of tumor somatic mutations revealed that circulating level of such tumor stem somatic mutations could reflect tumor burden and even predict prognosis earlier than traditional strategies. Furthermore, HCK (p.V174M), identified as a recurrent/metastatic related mutation site, could promote migration and invasion of HCC cells. Taken together, study of mutation profiles in biopsy and plasma samples in HCC patients showed that ctDNA could overcome tumor heterogeneity and real-time track the therapeutic responses in the longitudinal monitoring.

Synthesized attributes of water use by regional vegetation: a key to cognition of "water pump" viewpoint.

Recently, the frequent seasonal drought in Southwest China has brought considerable concerns and continuous heated arguments on the "water pump" viewpoint (i.e., the water demand from Hevea spp. and Eucalyptus spp. can be treated as a water pump) once again. However, such viewpoint just focused on water consumption from vegetation transpiration and its ecoenvironment impacts, which had not considered other attributes of vegetation, namely, water saving and drought resistance, and hydrological regulation (water conservation) into consideration. Thus, in this paper, the synthesized attributes of regional vegetation water use had been mainly discussed. The results showed that the study on such aspects as the characters of water consumption from vegetation transpiration, the potential of water saving and drought resistance, and the effects of hydrological regulation in Southwest China lagged far behind, let alone the report on synthesized attributes of water utilization with the organic combination of the three aspects above or the paralleled analysis. Accordingly, in this paper, the study on the synthesized attributes of water use by regional vegetation in Southwest China was suggested, and the objectives of such a special study were clarified, targeting the following aspects: (i) characters of water consumption from transpiration of regional typical artificial vegetation; (ii) potential of water saving and drought resistance of regional typical artificial vegetation; (iii) effects of hydrological regulation of regional typical artificial vegetation; (iv) synthesized attributes of water use by regional typical artificial vegetation. It is expected to provide a new idea for the scientific assessment on the regional vegetation ecoenvironment effects and theoretical guidance for the regional vegetation reconstruction and ecological restoration.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

[Effects of phytase Q9 on the yield and senescence characteristics of summer maize shaded in the field]. / æ¤é ¶Q9对大田遮阴夏玉米产量和衰老特性的调控作用.

Light shortage in the canopy of summer maize resulted from the decrease of solar radiation and the increase of planting density in Huanghuaihai region could reduce maize yield. In order to explore the effects of phytase Q9 on leaf senescence characteristics of summer maize, three sha-ding treatments with summer maize hybrid 'Denghai 605' (DH605) were conducted, including shading at flowering to maturity stage (S1), shading at ear stage (S2), and shading at whole growth stage (S3) with natural lighting in the field as control (CK). Chemical control reagent phytase Q9 was used to regulate the shading treatments (the original solution was diluted by 100 times) and the CK exogenously, namely shading at flowering to maturity stage-phytase Q9 (S1Q), shading at ear stage-phytase Q9 (S2Q), and shading at whole growth stage-phytase Q9 (S3Q), and natural lighting-phytase Q9 (CKQ), with spraying water at the same stage as the control. The results showed that leaf area index (LAI), soil-plant analysis development (SPAD) value and net photosynthetic rate of summer maize was significantly reduced by shading, which led to decreases of yield. The activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) in ear-leaf decreased. The content of malondialdehyde (MDA) and free proline increased, and that of soluble protein decreased. The spraying phytase Q9 significantly increased LAI, SPAD and net photosynthetic rate in S3Q and S2Q. MDA and free proline content in S3Q, S2Q, and S1Q were significantly decreased, and soluble protein content and POD activity was significantly increased. SOD and CAT activities in S2Q and S3Q were significantly increased. The yield of S3Q, S2Q and S1Q were 19%, 8% and 7% higher than that of S3, S2 and S1 respectively. There was no significant difference between CKQ and CK. In conclusion, phytase Q9 could effectively alleviate the negative impact of low light on yield formation of summer maize, and increase grain yield by improving photosynthetic capacity of leaves and delaying leaf senescence.

Identification of sokotrasterol sulfate as a novel proangiogenic steroid.

The potential to promote neovascularization in ischemic tissues using exogenous agents has become an exciting area of therapeutics. In an attempt to identify novel small molecules with angiogenesis promoting activity, we screened a library of natural products and identified a sulfated steroid, sokotrasterol sulfate, that induces angiogenesis in vitro and in vivo. We show that sokotrasterol sulfate promotes endothelial sprouting in vitro, new blood vessel formation on the chick chorioallantoic membrane, and accelerates angiogenesis and reperfusion in a mouse hindlimb ischemia model. We demonstrate that sulfation of the steroid is critical for promoting angiogenesis, as the desulfated steroid exhibited no endothelial sprouting activity. We thus developed a chemically synthesized sokotrasterol sulfate analog, 2beta,3alpha,6alpha-cholestanetrisulfate, that demonstrated equivalent activity in the hindlimb ischemia model and resulted in the generation of stable vessels that persisted following cessation of therapy. The function of sokotrasterol sulfate was dependent on cyclooxygenase-2 activity and vascular endothelial growth factor induction, as inhibition of either cyclooxygenase-2 or vascular endothelial growth factor blocked angiogenesis. Surface expression of alpha(v)beta(3) integrin was also necessary for function, as neutralization of alpha(v)beta(3) integrin, but not beta(1) integrin, binding abrogated endothelial sprouting and antiapoptotic activity in response to sokotrasterol sulfate. Our findings indicate that sokotrasterol sulfate and its analogs can promote angiogenesis in vitro and in vivo and could potentially be used for promoting neovascularization to relieve the sequelae of vasoocclusive diseases.

Uncialamycin, a new enediyne antibiotic.

[structure: see text] Laboratory cultures of an undescribed streptomycete obtained from the surface of a British Columbia lichen produce uncialamycin (1), a new enediyne antibiotic. The structure of uncialamycin (1) has been elucidated by analysis of spectroscopic data. Uncialamycin (1) exhibits potent in vitro antibacterial activity against gram-positive and gram-negative human pathogens, including Burkholderia cepacia, a major cause of morbidity and mortality in patients with cystic fibrosis.

A proteomic analysis of transplanted liver in a rat model of chronic rejection.

BACKGROUND: Chronic rejection (CR) is an important cause of liver allograft failure. In the latter condition, re-transplantation of the liver (ReLT) is the only option for survival. Unfortunately, with the current state of knowledge, it is difficult to diagnose and treat early CR. OBJECTIVE: To explore the biomarkers of the chronic rejection in orthotopic liver transplantation (OLT). METHODS: A rat model of chronic liver allograft rejection was established, and the differential protein expression in chronic allograft rejection (CR) was analyzed by iTRAQ-MALDI-TOF/TOF. RESULTS: Expression of sixty-two proteins was found to be significantly changed in CR rats. In the present study, CLU, Lcn2 and Krt19 were identified and quantified as early and reliable biomarkers for chronic rejection. CONCLUSION: Analysis of differential protein expression by iTRAQ-MALDI-TOF/TOF is a potentially effective method to help understand the mechanism of CR in orthotopic liver transplantation. The proteins CLU, Lcn2 and Krt19 might be potential prognostic markers for predicting chronic rejection after liver transplantation.

Spiculoic acids A and B, new polyketides isolated from the Caribbean marine sponge Plakortis angulospiculatus.

[structure: see text] Two novel polyketides, spiculoic acids A (1) and B (2), have been isolated from extracts of the Caribbean marine sponge Plakortisangulospiculatus. The structures of 1 and 2 were elucidated by detailed analysis of spectroscopic data. Spiculoic acid A (1) showed in vitro cytotoxicity against human breast cancer MCF-7 cells. It has a putative polyketide biogenetic origin that involves incorporation of four butyrate units and a Diels Alderase catalyzed intramolecular [4 + 2] cycloaddition reaction.

Functional secretion of a type 1 antifreeze protein analogue by optimization of promoter, signal peptide, prosequence, and terminator in Lactococcus lactis.

Lactococcus lactis is a food-grade microorganism of major commercial importance. Antifreeze protein is a potent cryogenic protection agent for the cryopreservation of food and pharmaceutical materials. In this study, extracellular expression of a novel recombinant type I antifreeze protein analogue (rAFP) in L. lactis was optimized. An efficient SlpA promoter (P SlpA) was fused to various signal peptides (SPs) and propeptide sequences to examine the extracellular expression levels of rAFP. An efficient signal peptide, SP sacB, fused to prosequence AE, enabled higher extracellular rAFP production; use of the SlpA terminator (Ter SlpA) was a further improvement. The extracellularly expressed rAFP successfully inhibited ice recrystallization and is thus potentially applicable for cryogenic preservation.