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| 1 | Levels of Metabolic Enzymes and Nitrogenous Compounds in the Swimming Crab Portunus trituberculatus Exposed to Elevated Ambient Ammonia-N显示文摘This study investigated the effects of ammonia-N(control and 1 and 5 mg L^(-1)) on the changes of metabolic enzymes activities and nitrogenous compounds levels in the gills, hepatopancreas, muscles, and hemolymph of the swimming crab Portunus trituberculatus. Results showed that the levels of hemolymph ammonia increased significantly at 6 h and then decreased to control level at 12 h. The activities of key enzymes involved in biosynthesis pathways of glutamine(Gln) and urea, such as glutamate dehydrogenase(GDH), glutamine synthetase(GS), and arginase(ARG), increased remarkably in different tissues of P. trituberculatus. Gln level was the highest in muscles, while urea content was the largest in hepatopancreas. The m RNA expression level of xanthine dehydrogenase(XDH) was downregulated sharply in gills but upregulated in the hepatopancreas and muscles. A small amount of uric acid was detected in the hemolymph. This result suggests that Gln in muscles may be used as an intermediary nitrogen repository, while urea may be primarily synthesized in the hepatopancreas and then transferred to other tissues via the hemolymph. Uric acid could be synthesized by the anabolism of purine nucleotides, in additon to the inhibitory activities of gills. In addition, the levels of Gln, urea and uric acid exhibited dose-and time-dependent effects with ammonia content. Therefore, P. trituberculatus could possibly convert ammonia into Gln, urea, or uric acid to detoxify ammonia during high ambient ammonia-N stress. | PAN Luqing SI Lingjun LIU Shengnan LIU Maoqi WANG Guohui | 2018 | Journal of Ocean University of China2018，17，4： | 5 |
| 2 | Transcriptomic response to ammonia-N stress in the hepatopancreas of swimming crab Portunus trituberculatus显示文摘The swimming crab Portunus trituberculatus is an important farmed species in China.Ammonia-N represents a major physiological challenge for crab culture and the hepatopancreas plays a major role in physiological adaptation processes.To better understand the molecular mechanism of the crab in response to ammonia-N stress,we performed a transcriptome analysis in the hepatopancreas of P.trituberculatus challenged with ammonia-N stress(5 mg/L),using the high-throughput sequencing technology.In total,52,280 unigenes were obtained from the hepatopancreas of P.trituberculatus,with an average length of 678 bp.Functional categorization and pathways showed some diiferentially expressed genes were involved in amino acid and nucleobase metabolism,energy metabolism,antioxidation,immune response,reproduction,moulting and material transport.The differential expression patterns of eight randomly selected annotated genes were validated by quantitative real-time PCR(qPCR).Results revealed a substantial number of genes modified by ammonia-N stress and a few significant ammonia acclimation pathways,which will serve as an invaluable resource for revealing the molecular basis of physiological adaptation mechanism in P.trituberculatus. | Lingjun Si Luqing Pan Hongdan Wang Xin Zhang | 2020 | Marine Life Science & Technology2020，2，2： | 0 |
| 3 | Ion Transport Signal Pathways Mediated by Neurotransmitter(Biogenic Amines) of Litopenaeus vannamei Under Low Salinity Challenge显示文摘The Pacific white shrimp, Litopenaeus vannamei, is widely farmed in China. Salinity is a major environmental factor that affects its growth and distribution. Crustacean hyperglycemic hormone is verified to participate in ion transport in response to the salinity challenge mediated by endocrine neurotransmitters(biogenic amines, BAs). In the present study, the contents of BAs and expressions of their receptors were detected in gills of Litopenaeus vannamei exposed to low salinity. The intracellular signaling molecules such as cyclic adenosine monophosphate(cAMP), protein kinase A(PKA), 14-3-3 protein, FXYD2 protein and cAMP response element-binding protein(CREB) were detected. The effects of low salinity on the expressions of Na^+-K^+-ATPase, Na^+/K^+/2 Cl-co-transporter and Cl-transporter and activity of Na^+-K^+-ATPase were also analyzed. The results showed that dopamine and epinephrine concentrations and their receptor expressions were significantly affected by low salinity. The changes of c AMP and PKA were obvious and the expressions of 14-3-3 and FXYD2 peaked at early stages. However, the expression of CREB was only significantly up-regulated on day 9. The activity and expression of Na^+-K^+-ATPase(α subunit) reached a peak on day 1. The expressions of Na^+/K^+/2 Cl-co-transporter and Cl-transporter up-regulated obviously. It suggests that BAs can activate the cAMP-PKA pathway, which further acts on the 14-3-3 and FXYD2 proteins, and ultimately improve the activity of Na^+-K^+-ATPase. Furthermore, after BAs stimulate the cAMP-PKA pathway, PKA phosphorylates the transcription factor CREB and regulates the expressions of ion transport enzymes/transporters. The results in this study are helpful for understanding the response mechanism of endocrine neurotransmitters on osmoregulation in crustaceans. | PAN Luqing SI Lingjun HU Dongxu | 2019 | Journal of Ocean University of China2019，18，1： | 0 |
| 4 | 评估帕博利珠单抗在中国晚期黑色素瘤患者中的应用:基于KEYNOTE-151研究的3年随访数据显示文摘中国肢端和黏膜黑色素瘤的发病率较高,但治疗选择有限,晚期黑色素瘤患者的生存率普遍较低。对Ib期KEYNOTE-151研究的初步分析显示,帕博利珠单抗在作为二线药物治疗中国晚期黑色素瘤患者中,表现出了良好的耐受性和优异的临床抗肿瘤活性。本研究分析了3年随访的研究数据,纳入一线治疗后进展的不可切除的III/IV期中国黑色素瘤患者,给予帕博利珠单抗2 mg/kg治疗,每3周1次,最长使用35剂。主要终点为安全性和客观缓解率(objective response rate,ORR);次要终点包括疗效维持时间(duration of response,DOR)、无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。根据RECIST v1.1标准,采用独立中心盲法评估患者疗效。此外,根据黑色素瘤亚型,以及BRAF突变状态和PD-L1表达状态(仅肢端黑色素瘤)进行亚组分析。本研究共纳入103例患者,中位随访时间[从首次用药到数据截止时间(2020年7月13日)]为44.6个月[四分位距(interquartile range,IQR):39.1–46.2]。85.4%的患者发生了任一级别的治疗相关不良事件(treatment-related adverse events,TRAEs),12.6%的患者发生了3/4级的TRAEs,无5级TRAE发生。3例患者因TRAEs(免疫相关肝炎、肺炎和关节炎)停药。免疫相关AEs和输液反应发生比例为34.0%(3/4级,2.9%)。ORR为17.6%(95%CI:10.8–26.4;1例完全缓解/17例部分缓解),中位DOR为13.8个月(范围:2.7–37.4+)。中位PFS为2.8个月(95%CI:2.7–3.5),36个月的PFS率为5.0%。中位OS为13.2个月(95%CI:10.4–16.5),36个月的OS率为22.3%。肢端黑色素瘤中位OS为14.8个月,非肢端皮肤黑色素瘤为13.5个月,黏膜黑色素瘤为7.4个月。在肢端黑色素瘤亚组中,程序性死亡配体-1(programmed death ligand-1,PD-L1)阳性的中位OS为22.8个月,PD-L1阴性的中位OS为8.4个月,BRAF野生型的中位OS为18.5个月,BRAF突变型的中位OS为5.8个月。综上,本研究对3年随访数据分析结果表明,帕博利珠单抗作为二线治疗在中国晚期黑色素瘤患者中的安全性可控,且达到了具有临床意义的抗肿瘤活性,使部分患者获得持久缓解。亚组分析表明PD-L1阳性和BRAF野生型的肢端黑色素瘤患者从该治疗中获益较大,但由于亚组样本量较小,该研究结论仍需进一步验证。 | Lu Si Xiaoshi Zhang Yongqian Shu Hongming Pan Di Wu Jiwei Liu Lili Mao Xuan Wang Xizhi Wen Yanhong Gu Lingjun Zhu Shijie Lan Xin Cai Scott J.Diede Haiyan Dai Cuizhen Niu Jianfeng Li Jun Guo 李雯钰(翻译校对) 斯璐(点评) | 2023 | 癌症2023，42，8： | 0 |
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