Identification of turkey biliary metabolites of ractopamine hydrochloride and the metabolism and distribution of synthetic [14C]ractopamine glucuronides in the turkey

1. The bile duct cannulated turkey poult (n = 3) dosed orally with [¹⁴C]ractopamine HCl {(1R*,3R*),(1R*,3S*)-4-hydroxy-α-[[[3-(4-hydroxy[¹⁴C]phenyl)-1-methylpropyl]-amino]methyl]-benzenemethanol hydrochloride; 19.9 mg; 9.28 μCi] excreted 37.46 12.1% (mean ± SD) of the administered radioactivity in bile by 24 h post-dosing. 2. A mono-glucuronide, conjugated at C-10 (the methylpropylamino phenol) of ractopamine, accounted for 76.6% of biliary radioactivity. 3. Urine collected from the colostomized turkey poult (n = 3) orally dosed with synthetic [¹⁴C]ractopamine-glucuronides (10.1 mg; 3.6 μCi) contained 11.96 1.0% (mean ± SD) of the administered radioactivity 24 h after dosing, indicating that some absorption of radioactivity occurred. Faeces contained 60.6% of the administered radioactivity and carcasses (with gastrointestinal tracts) contained 23.3% of the starting radioactivity. 4. Five colostomized poults were fitted with bile duct cannulas and were dosed intraduodenally with 10.2?mg (3.6 μCi) synthetic [¹⁴C]ractopamine-glucuronides. Urine and bile contained 15.5 ± 2.2 and 16.8 ± 2.1% respectively of the administered radiocarbon by 24 h post-dosing. Faeces contained 54.3% of the administered radioactivity. Total absorption of the dosed radioactivity averaged 33.4%. 5. Bile and urine collected from the colostomized, bile-duct cannulated bird contained mainly ractopamine glucuronides. Indirect evidence suggests that the dosed ractopamine glucuronides were not absorbed intact.     

Design,synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure–activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.     

Two isozymes of particulate methane monooxygenase with different methane oxidation kinetics are found in Methylocystis sp. strain SC2

Methane-oxidizing bacteria (methanotrophs) attenuate methane emission from major sources, such as wetlands, rice paddies, and landfills, and constitute the only biological sink for atmospheric methane in upland soils. Their key enzyme is particulate methane monooxygenase (pMMO), which converts methane to methanol. It has long been believed that methane at the trace atmospheric mixing ratio of 1.75 parts per million by volume (ppmv) is not oxidized by the methanotrophs cultured to date, but rather only by some uncultured methanotrophs, and that type I and type II methanotrophs contain a single type of pMMO. Here, we show that the type II methanotroph Methylocystis sp. strain SC2 possesses two pMMO isozymes with different methane oxidation kinetics. The pmoCAB1 genes encoding the known type of pMMO (pMMO1) are expressed and pMMO1 oxidizes methane only at mixing ratios >600 ppmv. The pmoCAB2 genes encoding pMMO2, in contrast, are constitutively expressed, and pMMO2 oxidizes methane at lower mixing ratios, even at the trace level of atmospheric methane. Wild-type strain SC2 and mutants expressing pmoCAB2 but defective in pmoCAB1 consumed atmospheric methane for >3 months. Growth occurred at 10-100 ppmv methane. Most type II but no type I methanotrophs possess the pmoCAB2 genes. The apparent K(m) of pMMO2 (0.11 muM) in strain SC2 corresponds well with the K(m(app)) values for methane oxidation measured in soils that consume atmospheric methane, thereby explaining why these soils are dominated by type II methanotrophs, and some by Methylocystis spp., in particular. These findings change our concept of methanotroph ecology.     

生活垃圾填埋场甲烷自然减排的新途径——厌氧与好氧的共氧化作用

通过证实生活垃圾填埋场中甲烷厌氧氧化与好氧氧化的共存,提出了甲烷自然减排的新途径.分别选取暴雨过后垃圾填埋表层30～60 cm的覆土、1.5 m以下的垃圾以及底层矿化垃圾做硫酸盐还原菌阳性反应实验,结果表明:生活垃圾填埋体不同填埋层都存在不同数量级的硫酸盐还原菌,且底层矿化垃圾中的硫酸盐还原菌的数量最多,表层覆土中最少...     

空间站甲烷流向变换蓄热催化燃烧反应器试验研究

目的 设计流向变换蓄热催化燃烧反应器,实现空间站低浓度甲烷的有效去除,并满足反应后气体低温排出的要求.方法 在70 L/min的气体输入情况下,催化剂温度500℃左右时,通过气体换向,使出口处甲烷浓度以及出口气体温度满足使用要求;蓄热体采用了堇青石,其热容量为750～900 J/(kg·℃),最高工作温度可达1350℃.结果 反应器换向时间约为8 min,反应器的出口气体温度控制在60℃以下,甲烷去除效率达到72％.结论 采用流向变换蓄热催化燃烧技术去除空间站低浓度甲烷、实现气体低温排出是可行的.     

重庆市黑石子填埋场渗沥液调节池改造项目初步设计探讨

针对重庆市黑石子填埋场原渗沥液调节池臭气污染、地下水导排能力不足以及底泥及漂浮物清淤等问题,拟对原调节池清淤,在原址上重新改造设计新调节池。新的调节池具有分区管理,加盖密封,沼气导排和处理功能。     

通过选择育种降低绵羊甲烷排放的研究进展

羊等反刍家畜是全球温室效应气体的重要贡献者,如何降低温室效应气体、尤其甲烷排放量已是畜牧业进一步发展面临的挑战之一。目前已提出许多减缓家畜甲烷排放的方法,而选择育种策略以其能形成持久、可累积的改变以及相对低的成本,成为主要候选方法。本文主要对利用选择育种方法降低羊甲烷排放量的相关研究进行综述,以便为今后该领域进一步的研究提供借鉴。     

The comparison of effects of processed Aconiti tuber, U50488H and MK-801 on the antinociceptive tolerance to morphine

In the previous studies, we demonstrated that an oriental herbal medicine, processed Aconiti tuber (PAT), at subanalgesic doses could inhibit or reverse the antinociceptive tolerance to morphine. In the present study, we compared the effect of PAT, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidin)cyclohexyl)-benzeneacetamide methane sulfonate hydrate (U50488H), a selective kappa opioid receptor (KOR) agonist, and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine-maleate (MK-801), a N-methyl-D-aspartate (NMDA) receptor antagonist, on the antinociceptive tolerance to morphine in the same experimental condition. Mice received subcutaneous morphine (10 mg/kg), and oral PAT at a subanalgesic dose (0.3 g/kg for mechanical or 1.0 g/kg for thermal test), or intraperitoneal U50488H at a subanalgesic dose (3 mg/kg), or MK-801 at a subanalgesic dose (0.1 mg/kg) once daily for 14 days. The mechanical nociceptive threshold was measured before, and at 60 min by tail pressure testing, and thermal nociceptive latency was measured before, and at 30 min by hot plate testing, after daily morphine injections. PAT and U50488H could not only inhibit the development of morphine tolerance but also reverse the already-developed morphine tolerance, while MK-801 could only inhibit the development of morphine tolerance but not reverse the already-developed morphine tolerance, in both mechanical and thermal nociceptive tests. These data suggested that PAT, an indirect-acting KOR agonist, share the common pharmacological property of KOR agonists on morphine tolerance, and that PAT may be superior to some NMDA receptor antagonists which do not reverse already-developed morphine tolerance.     

Improving Anti-Coking Properties of Ni/Al2O3 Catalysts via Synergistic Effect of Metallic Nickel and Nickel Phosphides in Dry Methane Reforming

A series of NiP-x/Al₂O₃ catalysts containing different ratio of metallic nickel to nickel phosphides, prepared by varying Ni/P molar ratio of 4, 3, 2 through a co-impregnation method, were employed to investigate the synergistic effect of metallic nickel-nickel phosphides in dry methane reforming reaction. The Ni/Al₂O₃ catalyst indicates good activity along with severe carbon deposition. The presence of phosphorus increases nickel dispersion as well as the interaction between nickel and alumina support, which results in smaller nickel particles. The co-existence of metallic nickel and nickel phosphides species is confirmed at all the P contained catalysts. Due to the relative stronger CO₂ dissociation ability, the NiP-x/Al₂O₃ catalysts indicate obvious higher resistance of carbon deposition. Furthermore, because of good balance between CH₄ dissociation and CO₂ dissociation, NiP-2/Al₂O₃ catalyst exhibits best resistance of carbon deposition, few carbon depositions were formed after 50 h of dry methane reforming.