TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR,blocks tumor angiogenesis

Angiogenesis is one of the most important processes for cancer cell survival, tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and its receptor, particularly VEGF receptor-2 (VEGFR-2, or kinase insert domain-containing receptor, KDR), play critical roles in tumor-associated angiogenesis. We developed TTAC-0001, a human monoclonal antibody against VEGFR-2/KDR from a fully human naïve single-chain variable fragment phage library. TTAC-0001 was selected as a lead candidate based on its affinity, ligand binding inhibition and inhibition of VEGFR-2 signal in human umbilical vein endothelial cells (HUVEC). TTAC-0001 inhibited binding of VEGF-C and VEGF-D to VEGFR-2 in addition to VEGF-A. It binds on the N-terminal regions of domain 2 and domain 3 of VEGFR-2. It could inhibit the phosphorylation of VEGFR-2/KDR and ERK induced by VEGF in HUVEC. TTAC-0001 also inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation in vitro, as well as ex vivo vessel sprouting from rat aortic rings and neovascularization in mouse matrigel model in vivo. Our data indicates that TTAC-0001 blocks the binding of VEGFs to VEGFR-2/KDR and inhibits VEGFR-induced signaling pathways and angiogenesis. Therefore, these data strongly support the further development of TTAC-0001 as an anti-cancer agent in the clinic.     

Circadian Variation in Cardiac Autonomic Activity: Reactivity Measurements to Different Types of Stressors

The role of endogenous circadian rhythmicity in autonomic cardiac reactivity to different stressors was investigated. A constant routine protocol was used with repeated exposure to a dual task and a cold pressor test. The 29 subjects were randomly divided into two groups in order to manipulate prior wakefulness. Group 1 started at 09:00 h immediately after a monitored sleep period, whereas group 2 started 12 h later. Measures of interbeat intervals (IBI), respiratory sinus arrythmia (RSA, a measure of parasympathetic activity), pre-ejection period (PEP, a measure of sympathetic activity), as well as core body temperature (CBT) were recorded continuously. Multilevel regression analyses (across-subjects) revealed significant (mainly 24 h) sinusoidal circadian variation in the response to both stressors for IBI and RSA, but not for PEP. Individual 24 + 12 h cosine fits demonstrated a relatively large interindividual variation of the phases of the IBI and RSA rhythms, as compared to that of the CBT rhythm. Sinusoidal by group interactions were found for IBI and PEP, but not for RSA. These findings were interpreted as an indication for endogenous circadian and exogenous parasympathetic (vagal) modulation of cardiac reactivity, while sympathetic reactivity is relatively unaffected by the endogenous circadian drive and mainly influenced by exogenous factors.     

Purification and Characterization,of Rice Bran Lipase II

A species of rice bran lipase (lipase II) was purified by ammonium sulfate precipitation, followed by successive chromatographies on DEAE-cellulose, Sephadex G–75 and CH-Sephadex C–50. Both polyacrylamide disc electrophoresis and ultracentrifugation demonstrated that the enzyme protein is homogeneous. The isoelectric point of the enzyme was 9.10 by ampholine electrophoresis. The sedimentation coefficient of the enzyme was evaluated to be 2.60 S, and the molecular weight to be 33,300 according to Archbald’s method. The enzyme showed the optimum pH between 7.5 and 8.0, and the optimum temperature at about 27°C. It was stable over the pH range from 5 to 9.5 and below 30°C. In substrate specificity, the enzyme exhibited a high specificity toward triglycerides having short-carbon chain fatty acids, although it was capable of hydrolyzing the ester bonds in the rice and olive oil.     

Ancient animal migration: a case study of eyeless,dimorphic Devonian trilobites from Poland

We report evidence of one of the oldest known animal migratory episodes in the form of queues of the eyeless trilobite Trimerocephalus chopini Kin & B?a?ejowski, from the Late Devonian (Famennian) of central Poland. In addition, there is evidence for two morphs in this population, one with nine segments and the other with ten. We infer that these queues represent mass migratory chains coordinated by chemotaxis, comparable to those observed in modern crustaceans such as spiny lobsters, and further suggest that the two forms, which occur in an approximately 1:1 ratio, may be dimorphs. These ancient arthropods may have migrated periodically to shallow marine areas for mass mating and spawning. The sudden death of the trilobites in the queues may have been caused by excess carbon dioxide and hydrogen sulphide introduced into the bottom water by distal storm disturbance of anoxic sediments. This study demonstrates the potential for further research on the evolution and ecology of aggregative behaviour in marine arthropods.     

慢阻肺患者运动负荷气道反应性与T细胞亚群的关系

摘要 目的：探讨与分析慢性阻塞性肺疾病（COPD）患者运动负荷气道反应性与T细胞亚群的关系。方法：2020年1月到2022年4月选择在本院诊治的慢阻肺患者88例作为慢阻肺组,同期选择在本院进行健康体检者88例作为健康组,检测两组T细胞亚群含量,判定两组的运动负荷气道反应性情况并进行相关性分析。结果：慢阻肺组的CD8⁺T淋巴细胞比例明显高于健康组,CD3⁺T淋巴细胞、CD4⁺T淋巴细胞比例明显低于健康组（P<0.05）。慢阻肺组的运动负荷气道反应性发生率为20.9 %,明显高于健康组的1.2 %（P<0.05）。在慢阻肺中,Spearsman分析显示运动负荷气道反应性发生率与CD3+T淋巴细胞、CD4⁺T淋巴细胞、CD8⁺T淋巴细胞比例存在相关性（P<0.05）。logistic回归分析显示CD3⁺T淋巴细胞、CD4⁺T淋巴细胞、CD8⁺T淋巴细胞比例都为影响运动负荷气道反应性发生的重要危险因素（P<0.05）。结论：慢阻肺患者多伴随有T细胞亚群异常,也多伴随有运动负荷气道反应性,运动负荷气道反应性与T细胞亚群存在相关性,也表明T细胞亚群紊乱是导致运动负荷气道反应性发生的重要因素。     

N-乙酰半胱氨酸抗脂多糖诱导的肺动脉损伤的研究

目的 :探讨N 乙酰半胱氨酸 (N acetylcysteine,NAC)减轻脂多糖 (lipopolysaccharide ,LPS)所致的肺损伤及其机制。方法 :应用血管环张力检测技术和扫描电镜方法 ,观察了NAC对LPS引起的肺动脉反应性及肺动脉内皮细胞超微结构变化的影响 ;并测定了肺动脉组织中丙二醛 (malondialhyde ,MDA)、超氧化物歧化酶 (superoxidedismutes ,SOD)及一氧化氮 (nitricoxide,NO)的变化。结果 :LPS(4μg/ml,7h)可降低肺动脉对乙酰胆碱 (ACh)介导的内皮依赖性舒张反应 ,NAC(0 .5mmol/L)可逆转此种反应降低而对正常肺动脉舒缩反应无明显影响 ;NAC可改善LPS引起的肺动脉内皮细胞超微结构损伤并可逆转LPS引起的肺动脉组织中MDA、NO含量增高和SOD活性降低。结论 :NAC可通过抗氧化作用保护肺动脉内皮细胞并增强肺动脉内皮依赖性舒张反应 ,提示此可能是其发挥抗肺动脉压增高从而改善内毒素所致肺损伤的机制之一。