HIV-1 Env三聚体抗原改造研究进展

HIV-1疫苗研发是当前艾滋病研究的一大热点,其病毒表面包膜糖蛋白Env三聚体介导病毒与细胞融合,是HIV-1疫苗研究的重要靶点。因此,设计并在体外表达类天然Env三聚体对HIV-1疫苗的研发具有重要的意义。近年来,Env三聚体研究取得了显著的进展。SOSIP、NFL2P、UFO等抗原改造方法实现了类天然Env三聚体的体外表达,逐步解决了改造抗原产量低、结构不稳定等问题,且表达的Env三聚体抗原能在动物免疫中诱导机体产生较高的中和抗体水平。Env三聚体改造方法促进了HIV-1疫苗的研究。文中综述了SOSIP、NFL2P、UFO三种HIV-1 Env三聚体抗原改造方法,对比各个改造方法优缺点,并结合自身工作提出相关建议,为后续HIV-1抗原的相关设计提供指导。     

二氢乳清酸脱氢酶的结构特征和催化循环研究进展

二氢乳清酸脱氢酶是黄素依赖的线粒体酶,它催化嘧啶从头合成的第4步反应,将二氢乳清酸氧化为乳清酸。通过选择性抑制二氢乳清酸脱氢酶,从而抑制嘧啶的合成,已被开发用于治疗癌症、自身免疫性疾病、细菌或病毒感染以及寄生虫疾病等。抑制剂的开发需详细了解二氢乳清酸脱氢酶的结构特征和催化循环机制。因此,文中主要从这两个方面进行了综述,并展望了该酶的抑制剂在临床应用中的前景。     

人乳寡糖2’-FL和3-FL的生物制备研究进展

人乳寡糖(Human milk oligosaccharides,HMO)是母乳中重要的免疫活性成分,对婴幼儿健康起到显著促进作用。2’-岩藻糖基乳糖(2’-FL)是HMO的主要组分,极具应用价值,3-岩藻糖基乳糖(3-FL)与2’-FL的合成途径相似,两者的研究具有相互借鉴意义,近年来针对它们的研究取得了较多进展。以微生物细胞工厂为核心理念的新型生物合成途径有望将2’-FL和3-FL产业化,未来将对乳制品行业产生重要的影响。文中综述了生物技术制备2’-FL和3-FL的最新研究进展,并对未来发展趋势进行了展望。     

微小型生物反应器及其在生物医药领域的应用展望

微小型生物反应器体积微小但在线分析检测和过程控制功能媲美台式装备。其核心支撑技术包括一次性材料及微加工技术、非接触式光学传感器、自动化以及实验设计(DOE)、数据分析软件与过程控制的整合。由于体积微小、湍流程度和单位能耗较低,微小型反应器内的混合、传质、剪切特性与工业规模设备有一定的区别。现阶段微小型生物反应器主要用于菌株和细胞系筛选和工艺优化,在实现高通量工艺的同时确保了数据的丰度,对缩短研发周期和加速产品上市,尤其是在应对突发性传染性疾病方面有着重要的意义。未来,精准医疗概念的落实也依赖功能柔性化的微小型生物反应器系统。     

A baseline epidemiological study of the co-infection of enteric protozoans with human immunodeficiency virus among men who have sex with men from Northeast China

BackgroundHuman immunodeficiency virus (HIV) and enteric parasite co-infection not only aggravates the clinical symptoms of parasites but also accelerates acquired immunodeficiency syndrome (AIDS) progression. However, co-infection research on men who have sex with men (MSM), the predominant high-risk population of HIV/AIDS in China, is still limited. In this study, we investigated the epidemiology of enteric parasites, risk factors, and associations with clinical significance in an MSM HIV/AIDS population in Heilongjiang Province, northeast China.MethodsWe recruited 308 MSMs HIV/AIDS patients and 199 HIV-negative individuals in two designated AIDS hospitals in Heilongjiang between April 2016 and July 2017. Fresh stool samples were collected. DNA extraction, molecular identification, and genotyping of Cryptosporidium species, Entamoeba histolytica, Cyclospora cayetanensis, Enterocytozoon bieneusi, and Blastocystis hominis were performed. Fourteen diarrhea-related pathogens were examined to exclude the influence of other bacterial pathogens on diarrhea incidence.Results31.5% of MSM HIV/AIDS participants were infected with at least one parasite species, a significantly higher proportion than that found in the HIV-negative individuals (2.5%). E. bieneusi presented the highest prevalence, followed by B. hominis, E. histolytica, Cryptosporidium spp., and C. cayetanensis. Warm seasons were the risk factor for parasitic infections in this population [odds ratio (OR) = 2.6, 95% CI: 1.47–4.57]. In addition, these individuals showed a higher proportion (35.8%) of present diarrhea (PD) compared with men who have sex with women (MSW) with HIV/AIDS (16.7%). The infection proportions of both Cryptosporidium spp. and E. histolytica were significantly higher in the PD. E. bieneusi infection was more prevalent in the historic diarrhea (HD) group. CD4⁺ T cell counts in the MSM patients with the above three parasites were significantly lower. New species and genotypes were found, and MSM patients had a wider range of species or genotypes.ConclusionsEnteric parasitic infection was prevalent in the MSM HIV/AIDS population, especially in patients with present diarrhea during warm seasons. E. histolytica and B. hominis should also be considered high-risk parasites for opportunistic infections in AIDS patients in addition to Cryptosporidium spp.     

Galectin-3 critically mediates the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting pyroptosis but not necroptosis signalling

We previously documented that M2-like macrophages exert a hepatoprotective effect in acute-on-chronic liver failure (ACLF) by inhibiting necroptosis signalling. Nevertheless, the molecular mechanism behind this hepatoprotection still needs to be further dissected. Galectin-3 (GAL3) has been reported to be critically involved in the pathogenesis of multiple liver diseases, whereas the potential role of GAL3 in ACLF remains to be explored. Herein, we hypothesised that GAL3 plays a pivotal role in the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting necroptosis. To test this hypothesis, we first assessed the expression of GAL3 in control and fibrotic mice with or without acute insult. Second, loss- and gain-of-function experiments of GAL3 were performed. Third, the correlation between GAL3 and M2-like macrophage activation was analysed, and the potential role of GAL3 in M2-like macrophage-conferred hepatoprotection was confirmed. Finally, the molecular mechanism underlying GAL3-mediated hepatoprotection was dissected. GAL3 was found to be obviously upregulated in fibrotic mice with or without acute insult but not in acutely injured mice. Depletion of GAL3 aggravated hepatic damage in fibrotic mice upon insult. Conversely, adoptive transfer of GAL3 provided normal mice enhanced resistance against acute insult. The expression of GAL3 is closely correlated with M2-like macrophage activation. Through adoptive transfer and depletion experiments, M2-like macrophages were verified to act as a major source of GAL3. Importantly, GAL3 was confirmed to hold a pivotal place in the hepatoprotection conferred by M2-like macrophages through loss- and gain-of-function experiments. Unexpectedly, the depletion and adoptive transfer of GAL3 resulted in significant differences in the expression levels of pyroptosis but not necroptosis signalling molecules. Taken together, GAL3 plays a pivotal role in the hepatoprotection conferred by M2-like macrophages in ACLF by inhibiting pyroptosis but not necroptosis signalling. Our findings provide novel insights into the pathogenesis and therapy of ACLF.Subject terms: Inflammasome, Necroptosis     

Mapping the habitat suitability of Ottelia species in Africa

Understanding the influence of environmental covariates on plant distribution is critical, especially for aquatic plant species. Climate change is likely to alter the distribution of aquatic species. However, knowledge of this change on the burden of aquatic macroorganisms is often fraught with difficulty. Ottelia, a model genus for studying the evolution of the aquatic family Hydrocharitaceae, is mainly distributed in slow-flowing creeks, rivers, or lakes throughout pantropical regions in the world. Due to recent rapid climate changes, natural Ottelia populations have declined significantly. By modeling the effects of climate change on the distribution of Ottelia species and assessing the degree of niche similarity, we sought to identify high suitability regions and help formulate conservation strategies. The models use known background points to determine how environmental covariates vary spatially and produce continental maps of the distribution of the Ottelia species in Africa. Additionally, we estimated the possible influences of the optimistic and extreme pessimistic representative concentration pathways scenarios RCP 4.5 and RCP 8.5 for the 2050s. Our results show that the distinct distribution patterns of studied Ottelia species were influenced by topography (elevation) and climate (e.g., mean temperature of driest quarter, annual precipitation, and precipitation of the driest month). While there is a lack of accord in defining the limiting factors for the distribution of Ottelia species, it is clear that water-temperature conditions have promising effects when kept within optimal ranges. We also note that climate change will impact Ottelia by accelerating fragmentation and habitat loss. The assessment of niche overlap revealed that Ottelia cylindrica and O. verdickii had slightly more similar niches than the other Ottelia species. The present findings identify the need to enhance conservation efforts to safeguard natural Ottelia populations and provide a theoretical basis for the distribution of various Ottelia species in Africa.     

Taxonomic synopsis of Berberis (Berberidaceae) from the northern Hengduan mountains region in China,with descriptions of seven new species

Though Berberis (Berberidaceae) is widely distributed across the Eurasian landmass it is most diverse in the Himalaya–Hengduan Mountain (HHM) region. There are more than 200 species in China where it is one of the most common mountain shrubs. The study on the taxonomy and evolution of Berberis in this region can thus provide an important insight into the origin and diversification of its flora. A prerequisite to this is mapping and describing the various species of Berberis in the region – a task that despite recent progress is by no means complete. It is clear that in China there may be a significant number of species still to be described and that even with published species much about their distribution remains to be discovered. As a contribution to the first of these tasks seven new species from the northern Hengduan Mountain of N. Sichuan and S. Qinghai: Berberis chinduensis, Berberis degexianensis, Berberis jiajinshanensis, Berberis jinwu, Berberis litangensis, Berberis longquensis and Berberis riparia, are described here. Differences in overall morphology and especially in floral structures with each other and with similar species of Berberis in the same region are presented. The report is the result of phylogenetic analyses based on plastome and partial nrDNA sequences of both the seven proposed new species and a significant number of similar species already published. Provisional conclusions as to the insights provides on the history of the genetic divergence are discussed.     

子宫内膜癌中的lncRNA-miRNA-mRNA ceRNA网络的整合分析

子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)是危害女性健康的癌症之一,但其发生发展机制尚不完全清楚.基因的异常表达在细胞癌变过程中发挥着重要的作用.本研究利用生物信息学方法对UCEC中异常表达的基因进行网络调控分析,为UCEC的机制研究及预后治疗提供理论依据.首先,利...