Rapid anti‐depressant‐like effects of ketamine and other candidates: Molecular and cellular mechanisms

Major depressive disorder takes at least 3 weeks for clinical anti‐depressants, such as serotonin selective reuptake inhibitors, to take effect, and only one‐third of patients remit. Ketamine, a kind of anaesthetic, can alleviate symptoms of major depressive disorder patients in a short time and is reported to be effective to treatment‐resistant depression patients. The rapid and strong anti‐depressant‐like effects of ketamine cause wide concern. In addition to ketamine, caloric restriction and sleep deprivation also elicit similar rapid anti‐depressant‐like effects. However, mechanisms about the rapid anti‐depressant‐like effects remain unclear. Elucidating the mechanisms of rapid anti‐depressant effects is the key to finding new therapeutic targets and developing therapeutic patterns. Therefore, in this review we summarize potential molecular and cellular mechanisms of rapid anti‐depressant‐like effects based on the pre‐clinical and clinical evidence, trying to provide new insight into future therapy.     

Research progress on gut health of farmers teleost fish: a viewpoint concerning the intestinal mucosal barrier and the impact of its damage

Reviews in Fish Biology and Fisheries - The intestinal mucosal barrier plays a critical role in the maintenance of host health. In farmed teleost fish, the intestinal epithelium is challenged by a...     

肝素C5异构酶的表达优化及分子改造

肝素和硫酸乙酰肝素是一类应用于临床抗凝血的糖胺聚糖。肝素葡萄糖醛酸C5异构酶(Heparosan-N-sulfate-glucuronate 5-epimerase,C5,EC 5.1.3.17) 是肝素和硫酸乙酰肝素合成过程中重要的修饰酶,催化N-硫酸化肝素前体 (N-sulfoheparosan) 的D-葡萄糖醛酸 (D-GlcA) 上5号位羧基翻转生成L-艾杜糖醛酸 (L-iduronic acid,L-IdoA)。文中以大肠杆菌Escherichia coli为宿主对斑马鱼来源的肝素葡萄糖醛酸C5异构酶基因Glce进行重组表达优化与分子改造。比较了3种不同的表达载体pET20b(+)、pET28a(+) 和pCold Ⅲ对C5表达的差异情况,其中以嗜冷启动型载体pCold Ⅲ表达酶活最高,达到(1 873.61±5.42) U/L。为了进一步提高C5的可溶表达量,在N端融合促溶标签SET2后,可溶蛋白表达量比对照提高了50%,酶活达到 (2 409.25±6.43) U/L。在此基础上,通过理性设计对底物结合口袋进行定点突变,获得最优突变体 (V153R) 的酶活和比酶活分别为 (5 804.32±5.63) U/L和(145.14±2.33) U/mg,是原始酶的2.41倍和2.28倍。肝素C5异构酶改造与表达优化为酶法催化合成肝素奠定了基础。     

肠激酶在毕赤酵母中的分泌表达优化

肠激酶 (Enterokinase,EK) 是一类特异性识别切割DDDDK序列的丝氨酸蛋白酶,作为一种工具酶广泛应用于生物医药领域。目前,EK在毕赤酵母Pichia pastoris中的表达水平较低,难以应用。本研究比较了6种不同的信号肽SP1、SP2、SP3、SP4、SP7和SP8对毕赤酵母分泌表达EK的影响。在摇瓶水平上,与α-factor信号肽相比,SP1信号肽显著提高了EK的分泌表达 (从6.8 mg/L提高至14.3 mg/L),酶活从 (2 390±212) U/mL提高至 (4 995±378) U/mL。在此基础上,通过共表达毕赤酵母内源蛋白Kex2,EK酶活提高至 (7 219±489) U/mL。另外,N端融合WLR三个氨基酸进一步提高酶活至 (15 145±920) U/mL,比酶活为 (1 174 600±53 100) U/mg。EK在毕赤酵母中的高效分泌表达为未来应用奠定了基础。     

枯草芽孢杆菌表达与调控工具相关研究进展

枯草芽孢杆菌作为革兰氏阳性模式微生物,由于其清晰的遗传背景、高效的分泌能力以及简单的培养条件等优势被广泛的应用于生物技术产业。近年来,随着代谢工程与合成生物学的发展,枯草芽孢杆菌相关表达系统与调控工具研究也取得了很大进展。围绕枯草芽孢杆菌动态调控工具的研究进展,分别从转录水平调控和转录后水平调控两个层面上进行综述,并对调控元件在生物技术中的应用进行了讨论。最后,对未来枯草芽孢杆菌表达与调控工具的发展进行了展望。     

全球中华鲎资源保护现状及对策建议

鲎是古老的海洋节肢动物。中华鲎(Tachypleus tridentatus)是世界现存4种鲎中体型最大的一种, 是河口生态系统的标志物种, 同时其血液被用于生产医用检验试剂――鲎试剂。中华鲎的自然地理分布范围相当狭窄, 仅局限于日本濑户内海向南延伸至印度尼西亚爪哇岛北岸以北的太平洋西岸海域, 其中在中国东岸和日本南部海域的历史产量较高。自20世纪50年代以来中华鲎种群数量出现了显著减少, 2019年中华鲎在IUCN红色名录中的濒危等级正式更新为濒危(EN), 明确了中华鲎资源呈现全球性衰退的状态, 究其原因可归纳为鲎生境破坏和过度捕捞两个方面。在开展鲎资源保护的实践工作中, 作者深刻反思当前鲎资源保护在海洋保护区划定、增殖放流及科普和野生动物保护法宣传中存在的问题并提出相应建议, 包括加快完善种群基线数据, 制定标准化种群和生境基线监测指南, 构建科学放流体系等, 以期推进全球范围内的中华鲎资源保护与科学管理。     

老年冠心病患者血尿酸水平与肠道菌群的关系

目的探讨老年冠心病患者血尿酸(SUA)水平与肠道菌群的关系,为该类患者的治疗提供参考。方法选择2018年5月至2019年5月我院收治的83例冠心病患者为研究组,选择同期我院83例健康体检者的作为对照组。比较两组对象SUA水平及粪便标本中肠道菌群分布情况(乳杆菌、双歧杆菌、幽门螺杆菌、大肠埃希菌、链球菌);比较不同菌群紊乱程度冠心病患者SUA水平;比较不同SUA水平冠心病患者肠道菌群分布情况。采用Pearson相关分析冠心病患者SUA水平与肠道菌群相关性。结果研究组患者肠道乳杆菌、双歧杆菌数量明显低于对照组(均P<0.05),而肠道幽门螺杆菌、大肠埃希菌、链球菌数量明显高于对照组(均P<0.05)。研究组患者SUA水平明显高于对照组(P<0.05),不同菌群紊乱程度冠心病患者SUA水平有差异有统计学意义(均P<0.05)。不同SUA水平冠心病患者肠道乳杆菌、双歧杆菌、幽门螺杆菌、大肠埃希菌、链球菌数量差异有统计学意义(均P<0.05)。冠心病患者SUA水平与肠道乳杆菌、双歧杆菌数量呈负相关(r=-0.872、-0.912,均P<0.001),与肠道幽门螺杆菌、大肠埃希菌、链球菌数量呈正相关(r=0.915、0.896、0.889,均P<0.001)。结论冠心病患者存在肠道细菌紊乱及高尿酸现象。冠心病患者SUA水平与肠道菌群显著相关,检测冠心病患者SUA水平对监测肠道菌群状态及治疗方案制定具有重要意义。     

Whole‐genome resequencing reveals the pleistocene temporal dynamics of Branchiostoma belcheri and Branchiostoma floridae populations

Global climatic fluctuations governed the ancestral demographic histories of species and contributed to place the current population status into a more extensive ecological and evolutionary context. Genetic variations will leave unambiguous signatures in the patterns of intraspecific genetic variation in extant species since the genome of each individual is an imperfect mosaic of the ancestral genomes. Here, we report the genome sequences of 20 Branchiostoma individuals by whole‐genome resequencing strategy. We detected over 140 million genomic variations for each Branchiostoma individual. In particular, we applied the pairwise sequentially Markovian coalescent (PSMC) method to estimate the trajectories of changes in the effective population size (N_e) of Branchiostoma population during the Pleistocene. We evaluated the threshold of sequencing depth for proper inference of demographic histories using PSMC was ≥25×. The PSMC results highlight the role of historical global climatic fluctuations in the long‐term population dynamics of Branchiostoma. The inferred ancestral N_e of the Branchiostoma belcheri populations from Zhanjiang and Xiamen (China) seawaters was different in amplitude before the first (mutation rate = 3 × 10^?9) or third glaciation (mutation rate = 9 × 10^?9) of the Pleistocene, indicating that the two populations most probably started to evolve in isolation in their respective seas after the first or third glaciation of the Pleistocene. A pronounced population bottleneck coinciding with the last glacial maximum was observed in all Branchiostoma individuals, followed by a population expansion occurred during the late Pleistocene. Species that have experienced long‐term declines may be especially vulnerable to recent anthropogenic activities. Recently, the industrial pollution and the exploitation of sea sand have destroyed the harmonious living environment of amphioxus species. In the future, we need to protect the habitat of Branchiostoma and make full use of these detected genetic variations to facilitate the functional study of Branchiostoma for adaptation to local environments.     

Screening and heterologous expression of flavone synthase and flavonol synthase to catalyze hesperetin to diosmetin

Biotechnology Letters - In this study, 44 flavone synthases (FNS) and flavonol synthases (FLS) from different origins were collected. The instability index and conserved domain of the enzymes were...