Construction of a high density integrated genetic map for cucumber (Cucumis sativus L.)

The high-density consensus map was constructed based on the GY14 × PI 183967 map from an inter-subspecific cross and the extended S94 × S06 map from an intra-subspecific cross. The consensus map was composed of 1,369 loci, including 1,152 SSR loci, 192 SRAP loci, 21 SCAR loci and one STS locus as well as three gene loci of fruit external quality traits in seven chromosomes, and spanned 700.5 cM, of which 682.7 cM (97.5%) were covered by SSR markers. The average genetic distance and physical interval between loci were 0.51 cM and ~268 kbp, respectively. Additionally, the physical position of the sequence-associated markers aligned along the assembled cucumber genome sequence established a relationship between genetic maps and cucumber genome sequence and to a great extent validated the order of markers in individual maps and consensus map. This consensus map with a high marker density and well-ordered markers is a saturated and reliable linkage map for genetic analysis of cucumber or the Cucurbitaceae family of plants.     

Effect of Methamphetamine on Spectral Binding,Ligand Docking and Metabolism of Anti-HIV Drugs with CYP3A4

Cytochrome P450 3A4 (CYP3A4) is the major drug metabolic enzyme, and is involved in the metabolism of antiretroviral drugs, especially protease inhibitors (PIs). This study was undertaken to examine the effect of methamphetamine on the binding and metabolism of PIs with CYP3A4. We showed that methamphetamine exhibits a type I spectral change upon binding to CYP3A4 with δA_max and K_D of 0.016±0.001 and 204±18 μM, respectively. Methamphetamine-CYP3A4 docking showed that methamphetamine binds to the heme of CYP3A4 in two modes, both leading to N-demethylation. We then studied the effect of methamphetamine binding on PIs with CYP3A4. Our results showed that methamphetamine alters spectral binding of nelfinavir but not the other type I PIs (lopinavir, atazanavir, tipranavir). The change in spectral binding for nelfinavir was observed at both δA_max (0.004±0.0003 vs. 0.0068±0.0001) and K_D (1.42±0.36 vs.2.93±0.08 μM) levels. We further tested effect of methamphetamine on binding of 2 type II PIs; ritonavir and indinavir. Our results showed that methamphetamine alters the ritonavir binding to CYP3A4 by decreasing both the δA_max (0.0038±0.0003 vs. 0.0055±0.0003) and K_D (0.043±0.0001 vs. 0.065±0.001 nM), while indinavir showed only reduced K_D in presence of methamphetamine (0.086±0.01 vs. 0.174±0.03 nM). Furthermore, LC-MS/MS studies in high CYP3A4 human liver microsomes showed a decrease in the formation of hydroxy ritonavir in the presence of methamphetamine. Finally, CYP3A4 docking with lopinavir and ritonavir in the absence and presence of methamphetamine showed that methamphetamine alters the docking of ritonavir, which is consistent with the results obtained from spectral binding and metabolism studies. Overall, our results demonstrated differential effects of methamphetamine on the binding and metabolism of PIs with CYP3A4. These findings have clinical implication in terms of drug dose adjustment of antiretroviral medication, especially with ritonavir-boosted antiretroviral therapy, in HIV-1-infected individuals who abuse methamphetamine.     

百日咳杆菌粘附素对猪源支气管败血波氏杆菌的保护性抗原的筛选

摘要：【目的】本研究通过百日咳杆菌黏附素(PRN)基因的分段克隆表达及其在BALB/c小鼠的主动和被动免疫保护试验筛选PRN中的保护性抗原肽。【方法和结果】利用大肠杆菌进行PRN的完整蛋白、N端和C端多肽及其RI和RII区域多肽（双拷贝）的表达,命名为GST-PRN、GST-PN、GST-PC、GST-2PRI和GST-2PRII。Western blot检测证实5种表达产物均具有良好的反应原性。在主动免疫保护试验中,5种表达产物均能诱导小鼠产生较高的PRN抗体水平;当使用3 LD50的支气管败血波氏杆菌     

半连续灌注培养中杂交瘤细胞的生长和代谢

考察了在半连续灌注培养中WuT₃杂交瘤细胞在不同灌注速率下细胞生长的动态变化,培养基中主要基质的消耗和代谢物的生成。当灌注速率D从1.0/d升高到2.0/d时,乳酸得率系数Y_lac/glu降低18%,氨得率系数Y_amm/gln降低40%,丙氨酸得率系数Y_ala/gln升高58%,甘氨酸得率系数Y_gly/gln基本恒定。说明在灌注速率升高的条件下,细胞会调整代谢机制,丙酮酸和过量的谷氨酸通过转氨作用生成丙氨酸而非甘氨酸。     

Effects of sodium glucose cotransporter-2 inhibitors on serum uric acid in type 2 diabetes mellitus: A systematic review with an indirect comparison meta-analysis

To describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, and CENTRAL were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to Aug 10, 2017, without language or date restrictions. Thirty-one studies totaling 13,650 patients were included. SGLT2 inhibitors significantly decreased SUA levels compared with placebo, canagliflozin WMD –37.02?μmol/L, 95% CI [–38.41, –35.63], dapagliflozin WMD –38.05?μmol/L, 95% CI [–44.47, –31.62], empagliflozin WMD –42.07?μmol/L, 95% CI [–46.27, –37.86]. The drug class effect of SUA reduction suggesting SGLT2 inhibitors might be beneficial for diabetic patients with hyperuricemia.     

钙蛋白酶介导模拟失重大鼠心肌肌钙蛋白抑制亚基的降解

本文旨在观察尾部悬吊模拟失重大鼠心肌钙蛋白酶(calpain)与钙蛋白酶抑素(calpastatin)表达的变化,以探讨心肌肌钙蛋白抑制亚基(cardiac troponin I,cTnI)降解的可能机制。采用尾部悬吊模拟失重大鼠模型,Western blotting技术观测心肌calpain-1、calpain-2与calpastatin的表达;PD150606抑制calpain活性,分析cTnI降解程度的变化。结果显示:与同步对照组相比,悬吊2周与4周组大鼠心肌calpastatin表达呈显著性降低(P0.05),calpain-1表达未改变,calpain-2表达略有降低;但是,心肌calpain-1/calpastatin及calpain-2/calpastatin的比值在悬吊2周与4周组明显增高(P0.05,P0.01)。悬吊4周组cTnI降解显著高于对照组(P0.01);然而,用calpain非特异性抑制剂PD150606处理后,对照组及悬吊组cTnI的降解均被显著抑制(P0.01)。这些结果提示模拟失重大鼠心肌calpain活性增高可能增加cTnI的降解。     

Effect of metallothionein on cell viability and its interactions with cadmium and zinc in HEK293 cells

Metallothioneins (MTs) are thought to participate in a wide variety of physiological roles, but the mechanisms involved are still unclear. The study was designed to examine the possible factors related to these mechanisms. Methods, including transfection, MTT assay and flow cytometry, were used to investigate the effect of MTs on cell viability and their interactions with cadmium and zinc in HEK293 cells. The results showed that transient overexpression of human MT1A, MT2 and MT3 genes dynamically affected cell viability, and the effect was influenced by zinc and cadmium ions. Overexpressed MTs with added zinc showed a greater inhibitory effect on cell viability. Overexpressed MTs protected cells against low concentrations of cadmium ions (10 microM), but increased cell death in response to high concentrations (20-50 microM). Out of the three MTs, MT1A was more efficient than MT2 and MT3 in its resistance to cadmium (10 microM), and MT3 together with zinc showed more cell growth inhibition than MT1 and MT2. These results indicate that both of the divalent metal ions that could bind MTs, as well as the individual MT isoforms, affect the role of MTs on cell viability, which may explain in part why the comprehensive effect of MTs on the cells was elusive.     

The first species of Hapalodectes (Mesonychia,Mammalia) from the middle Paleocene of China (Qianshan Basin,Anhui Province) sheds light on the initial radiation of hapalodectids

A lower jaw of the mesonychian Hapalodectes is reported from Nongshanian sediments (Upper Doumu Formation; middle Paleocene) of the Qianshan Basin (Anhui Province, China). The fragmentary mandible is only the third specimen of Hapalodectidae discovered in Paleocene deposits, and the first in south east China; it is moreover the oldest, the two other specimens having been found in Gashatan (late Paleocene) localities. The premolars and molars of the new fossil are morphologically similar to Hapalodectes dux (late Paleocene of Mongolia), which has been considered to be the most primitive hapalodectid, but their relative proportions recall H. paleocenus and the Eocene Hapalodectes species. As a result, the fossil described herein appears to be different from the other previously described species of Hapalodectes in being morphologically intermediate between H. dux and the other Hapalodectes species, notably the Bumbanian Hapalodectes hetangensis and H. huanghaiensis from China; it is thus identified as a new species, Hapalodectes lopatini (possibly a male individual). Its discovery is important because it sheds light on the initial radiation of hapalodectids. The presence of one primitive hapalodectid in Mongolia previously suggested the Mongolian Plateau as the centre of origination of this carnivorous family, but the discovery of H. lopatini in older sediments from south‐east China challenges this hypothesis. In the earliest Eocene, Hapalodectes dispersed from Asia to North America; this event being part of the ‘East of Eden’ dispersals. This event resulted in the geographical separation of two distinct Hapalodectes groups, in North America and south‐eastern China respectively.