露地栽培向设施栽培转变对菜田土壤重金属含量及形态的影响

为了研究露地栽培向设施大棚栽培转变对土壤重金属含量的影响,对武汉市郊区露地和设施塑料大棚两种栽培条件下菜田土壤重金属Cd、Cr和Pb各形态含量及分布特征进行了研究。结果显示,露地和大棚栽培条件下土壤重金属元素Cr和Pb各种形态含量之间没有明显差异,但Cd各种形态含量间有显著差异;从露地到大棚,土壤中Cd酸可提取态含量从露地的0.62 mg/kg上升到大棚的1.19 mg/kg,其次是Cd残渣态、有机结合态、氧化态和碳酸盐结合态;Cd总含量从露地的0.79 mg/kg升高到大棚的1.58 mg/kg,显著超过土壤环境质量标准中的Cd含量标准值(0.3 mg/kg),达到严重污染水平。Cd碳酸盐结合态和氧化态占总量的比例有所降低,而酸可提取态占总量的比例有所升高。说明从露地到设施大棚栽培,促使了土壤中部分Cd碳酸盐结合态和氧化结合态向酸可提取态转变,提高了土壤中Cd的生物有效性。因此,在设施大棚栽培快速发展的情况下,要加强重金属Cd对土壤污染的治理,减少重金属Cd对蔬菜的毒害。     

Biochemical Characterization of Individual Human Glycosylated pro-Insulin-like Growth Factor (IGF)-II and big-IGF-II Isoforms Associated with Cancer

Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed “pro” and “big” IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling.     

The composition and bioavailability of phosphorus transport through the Changjiang (Yangtze) River during the 1998 flood

Water and suspended sediment (SS) samples were collected from the Changjiang River at the Datong Hydrological Station (DHS), five times from May 1997 through January 1999 in order to evaluate transport, composition and bioavailability of phosphorus (P) during a 1998 flood. Transport of most of the phosphorus compositions was substantially higher during the 1998 flood than at other sampling dates. Phosphorus associated with suspended sediment (TPP) accounted for more than 85% of total phosphorus (TP) transport during periods of preflood and flood. The high transport of TPP during the flood was due to unusually high concentrations of TPP and sediment discharge. The potentially bioavailable phosphorus in SS (PBAP) accounted for about 10% of TPP. PBAP with dissolved inorganic phosphorus (DIP) consisted of 15–89% of TP. For all the sampling dates, the concentrations of potential bioavailable phosphorus (BAP) ranged from 0.035–0.08 mg L^–1, significantly higher than the limiting concentration for eutrophication. Therefore, the increasing temporal trends of TP concentration and high bioavailability of TP appear to support more frequent algal blooms in receiving East China Sea coastal waters in recent years. Hence, the underestimate of TPP transport by large rivers may also underestimate the biogeochemical cycling of other associated nutrients, such as nitrogen and carbon.     

Microbial immobilization of cadmium released from CdO in the soil

The effect of microorganisms on the fate of Cd introduced into the soil as cadmium oxide (CdO) was investigated. Cadmium oxide (875 µg Cd per gram of soil) was added to -irradiated (sterile) and non-sterile soils. The soils were incubated for 90 days at 18 °C under aerobic conditions with moisture kept at 60% of water-holding capacity. Half of the samples in each treatment were supplemented with starch (0.5%, w/w) in order to stimulate microbial growth in the non-sterile soil. After various time intervals (7- or 10-day), soil samples from each treatment were extracted with deionized distilled water (ratio 1:40) or 0.25 M CaCl₂ (ratio 1:5). The results indicated that during the incubation period the amount of Cd extracted from the non-sterile soil with either solvent was markedly lower than that extracted from the -irradiated sterile control. The addition of starch to the non-sterile soil reduced the concentration of Cd in the 0.25 M CaCl₂ extracts without affecting the Cd-content in the water extracts. Short-term experiments in which Cd was added to the soil as a solution of Cd(NO₃)₂ indicated that irradiation did not affect the sorption of Cd to the soil. The addition of bacterial mass (1 mg of dry weight g^–1 soil) decreased the amount of Cd extracted with water as well as that extracted with 0.25 M CaCl₂. Under sterile conditions the solubility of CdO in soil extracts was higher than in the other extractants. The addition of glucose (0.5%, w/w) or a glucose/starch mixture (0.5%, w/w of each) to the sterile soil increased the amount of extractable Cd after a short incubation (18 h at 18 °C). The obtained results suggest that primarily physicochemical reactions are involved in dissolving CdO in the soil but that microbial activity may be responsible for the immobilization of the released metal.     

太湖不同解有机磷菌株胞外碱性磷酸酶活性对蓝藻碎屑的响应

浮游细菌胞外碱性磷酸酶在湖泊磷循环过程中具有关键作用, 但其与生物可利用性磷和颗粒态有机质之间的关系尚未得到充分的研究。研究以从太湖沉积物分离的3 株解有机磷细菌(OPB)和东湖水中OPB菌群为实验对象, 以蓝藻干物质为颗粒态有机质, 系统分析了模拟条件下OPB 的数量、不同大小颗粒所表现的胞外碱性磷酸酶活性(APA)与不同形态磷的浓度及其相互关系。从总体上讲, APA 与OPB 数量显著正相关, 且明显反比于溶解反应性磷(SRP)浓度, 在模拟实验过程中, 不同菌株(群)所对应的SRP 浓度均显著不同, 故其解磷能力各异。从绝对活性及其在总活性中所占的比例来看, 各处理间小颗粒(0.22—3.0 μm)APA亦明显不同, 而大颗粒(>3.0 μm)APA和溶解态(8 CFU/mL), SRP 浓度逐渐增加。实验后期(20—33 d)细菌数量大幅度减少, 且伴随SRP 和溶解态有机磷浓度的显著升高。因此, 在缺磷且富含颗粒态有机质的条件下, OPB 将产生胞外碱性磷酸酶, 分解有机磷, 进而满足其大量生长的需要, 同时有效改变溶解态磷的形态与生物可利用性。       

Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists

A weak antagonist of the pyrimidinergic receptor P2Y₁₄ containing a dihydropyridopyrimidine core was identified through high-throughput screening. Subsequent optimization led to potent, non-UTP competitive antagonists and represent the first reported non-nucleotide antagonists of this receptor. Compound 18q was identified as a 10 nM P2Y₁₄ antagonist with good oral bioavailability and provided sufficient exposure in mice to be used as a tool for future in vivo studies.     

Optimization of a series of potent,selective and orally bioavailable SYK inhibitors

Spleen tyrosine kinase (SYK) is a non-receptor cytosolic kinase. Due to its pivotal role in B cell receptor and Fc-receptor signaling, inhibition of SYK has been targeted in a variety of disease areas. Herein, we report the optimization of a series of potent and selective SYK inhibitors, focusing on improving metabolic stability, pharmacokinetics and hERG inhibition. As a result, we identified 30, which exhibited no hERG activity but unfortunately was poorly absorbed in rats and mice. We also identified a SYK chemical probe, 17, which exhibits excellent potency at SYK, and an adequate rodent PK profile to support in vivo efficacy/PD studies.