麻疹疫苗生产连续培养多次收获工艺研究

本研究对连续培养多次收获工艺用于麻疹疫苗生产的可行性、疫苗维持液保护剂、冻干保护剂及冻干过程等进行了大量反复试验,结果表明在现行条件下,本生产工艺具有重复性好、成本低、投入产出率高、易于质量控制等优势。对本工艺生产疫苗进行全面检定,表明成品滴度和稳定性试验指标等均高于９０版《生物制品规程》要求,并在试验基础上制定出了生产工艺流程。     

Repeated horizontal gene transfer of GALactose metabolism genes violates Dollo’s law of irreversible loss

Dollo’s law posits that evolutionary losses are irreversible, thereby narrowing the potential paths of evolutionary change. While phenotypic reversals to ancestral states have been observed, little is known about their underlying genetic causes. The genomes of budding yeasts have been shaped by extensive reductive evolution, such as reduced genome sizes and the losses of metabolic capabilities. However, the extent and mechanisms of trait reacquisition after gene loss in yeasts have not been thoroughly studied. Here, through phylogenomic analyses, we reconstructed the evolutionary history of the yeast galactose utilization pathway and observed widespread and repeated losses of the ability to utilize galactose, which occurred concurrently with the losses of GALactose (GAL) utilization genes. Unexpectedly, we detected multiple galactose-utilizing lineages that were deeply embedded within clades that underwent ancient losses of galactose utilization. We show that at least two, and possibly three, lineages reacquired the GAL pathway via yeast-to-yeast horizontal gene transfer. Our results show how trait reacquisition can occur tens of millions of years after an initial loss via horizontal gene transfer from distant relatives. These findings demonstrate that the losses of complex traits and even whole pathways are not always evolutionary dead-ends, highlighting how reversals to ancestral states can occur.     

Knockout of Akt1/2 suppresses the metastasis of human prostate cancer cells CWR22rv1 in vitro and in vivo

Although primary androgen deprivation therapy resulted in tumour regression, unfortunately, majority of prostate cancer progress to a lethal castration-resistant prostate cancer, finally die to metastasis. The mutual feedback between AKT and AR pathways plays a vital role in the progression and metastasis of prostate cancer. Therefore, the treatment of a single factor will eventually inevitably lead to failure. Therefore, better understanding of the molecular mechanisms underlying metastasis is critical to the development of new and more effective therapeutic agents. In this study, we created prostate cancer CWR22rv1 cells with the double knockout of Akt1 and Akt2 genes through CRISPR/Cas9 method to investigate the effect of Akt in metastasis of prostate cancer. It was found that knockout of Akt1/2 resulted in markedly reduced metastasis in vitro and in vivo, and appeared to interfere AR nuclear translocation through regulating downstream regulatory factor, FOXO proteins. It suggests that some downstream regulatory factors in the AKT and AR interaction network play a vital role in prostate cancer metastasis and are potential targeting molecules for prostate cancer metastasis treatment.     

Acute Mechanical Stretch Promotes eNOS Activation in Venous Endothelial Cells Mainly via PKA and Akt Pathways

In the vasculature, physiological levels of nitric oxide (NO) protect against various stressors, including mechanical stretch. While endothelial NO production in response to various stimuli has been studied extensively, the precise mechanism underlying stretch-induced NO production in venous endothelial cells remains incompletely understood. Using a model of continuous cellular stretch, we found that stretch promoted phosphorylation of endothelial NO synthase (eNOS) at Ser¹¹⁷⁷, Ser⁶³³ and Ser⁶¹⁵ and NO production in human umbilical vein endothelial cells. Although stretch activated the kinases AMPKα, PKA, Akt, and ERK1/2, stretch-induced eNOS activation was only inhibited by kinase-specific inhibitors of PKA and PI3K/Akt, but not of AMPKα and Erk1/2. Similar results were obtained with knockdown by shRNAs targeting the PKA and Akt genes. Furthermore, inhibition of PKA preferentially attenuated eNOS activation in the early phase, while inhibition of the PI3K/Akt pathway reduced eNOS activation in the late phase, suggesting that the PKA and PI3K/Akt pathways play distinct roles in a time-dependent manner. Finally, we investigated the role of these pathways in stretch-induced endothelial exocytosis and leukocyte adhesion. Interestingly, we found that inhibition of the PI3K/Akt pathway increased stretch-induced Weibel-Palade body exocytosis and leukocyte adhesion, while inhibition of the PKA pathway had the opposite effects, suggesting that the exocytosis-promoting effect of PKA overwhelms the inhibitory effect of PKA-mediated NO production. Taken together, the results suggest that PKA and Akt are important regulators of eNOS activation in venous endothelial cells under mechanical stretch, while playing different roles in the regulation of stretch-induced endothelial exocytosis and leukocyte adhesion.     

An In Situ Interface Reinforcement Strategy Achieving Long Cycle Performance of Dual‐Ion Batteries

Dual‐ion batteries (DIBs) with high operation voltage offer promising candidates for low‐cost clean energy chemistries. However, there still exist tough issues, including structural collapse of the graphite cathode due to solvent co‐intercalation and electrolyte decomposition on the electrode/electrolyte interface, which results in unsatisfactory cyclability and fast battery failure. Herein, Li₄Ti₅O₁₂ (LTO) modified mesocarbon microbeads (MCMBs) are proposed as a cathode material. The LTO layer functions as a skeleton and offers electrocatalytic active sites for in situ generation of a favorable and compatible cathode electrolyte interface (CEI) layer. The synergetic LTO‐CEI network can change the thermodynamic behavior of the PF₆^? intercalation process and maintain the structural integrity of the graphite cathode, as a “Great Wall” to protect the cathode from structural collapse and electrolyte decomposition. Such LTO‐CEI reinforced cathode exhibits a prolonged cyclability with 85.1% capacity retention after 2000 cycles even at cut‐off potential of 5.4 V versus Li⁺/Li. Moreover, the LTO‐modified MCMB (+)//prelithiated MCMB (?) full cell exhibits a high energy density of ≈200 Wh kg^?1, remarkably enhanced cyclability with 93.5% capacity retention after 1000 cycles. Undoubtedly, this work offers in‐depth insight into interface chemistry, which can arouse new originality to boost the development of DIBs.     

太行山猕猴髋臼性别二态性研究

本文使用几何形态测量法探讨42例成年太行山猕猴Macaca mulatta tcheliensis髋臼的性别二态性。结果显示,太行山猕猴雌雄个体的髋臼形态具有明显的性别二态性,利用髋臼可以正确判别92.3%的雌性和87.5%的雄性个体。髋臼的形态差异主要分布于月状面的后上部,即与髋臼切迹相对的月状面区域的宽度表现为雄性大于雌性,另外雄性髋臼大小的波动范围也比雌性更广。造成髋臼性别二态性的生物学原因可能与其功能有关,髋臼作为髋关节的组成部分,起着支撑身体和协同运动的功能,能够优化关节接触面的压力分布。推测雄性髋臼受到的体质量压力更大可能是雄性进化出比雌性更宽大的月状面的主要原因。