光免疫治疗的抗肿瘤研究进展

光免疫治疗是一种新兴的肿瘤靶向光疗手段,它将单克隆抗体的肿瘤特异性与光吸收剂的光毒性相结合,可以快速且极具免疫原选择性地诱导靶肿瘤细胞的死亡。由于靶向性强,光免疫治疗的副作用小。而且因为该疗法诱导的免疫原性死亡会引起垂死肿瘤细胞周围未成熟树突状细胞的快速成熟,继而将肿瘤抗原提呈给CD8+T细胞,导致治疗后CD8+T细胞的激活和增殖,增强宿主抗肿瘤免疫反应。不仅如此,光免疫治疗还能通过增强纳米药物的肿瘤组织穿透性而提高疗效。鉴于光免疫治疗的优良应用前景,文中从其免疫激活机制、超级高渗透长滞留效应、新进展与联合治疗等方面进行综述,旨在为其深入研究和临床转化提供参考。     

氧死亡:一种新型调节性细胞死亡

氧死亡(oxeiptosis)是2018年提出的一种新的调节性细胞死亡方式(regulated cell death, RCD)。其特点是活性氧诱导的Caspase非依赖性的凋亡样细胞死亡。它有自身独特的损伤诱因(活性氧)、关键基因与通路(KEAP1-PGAM5-AIFM1),不同于坏死、细胞凋亡、坏死性凋亡、焦亡、铁死亡等其他的细胞死亡方式。本文就从氧死亡的历史、特点、主要通路、鉴别等方面作一综述。     

子宫内膜异位细胞改良体外培养技术的研究进展

体外细胞培养是子宫内膜异位性疾病研究的重要工具。本文回顾了细胞体外培养技术在分离、纯化环节的改良以及子宫内膜异位性疾病永生化细胞系改造中的研究进展,并总结了近几年来激素及细胞因子诱导培养、细胞共培养及三维培养技术在该疾病体外机制研究中的应用,并对其发展前景进行了展望。     

Phosphofructokinase relocalizes into subcellular compartments with liquid-like properties in vivo

Although much is known about the biochemical regulation of glycolytic enzymes, less is understood about how they are organized inside cells. We systematically examine the dynamic subcellular localization of glycolytic protein phosphofructokinase-1/PFK-1.1 in Caenorhabditis elegans. We determine that endogenous PFK-1.1 localizes to subcellular compartments in vivo. In neurons, PFK-1.1 forms phase-separated condensates near synapses in response to energy stress from transient hypoxia. Restoring animals to normoxic conditions results in cytosolic dispersion of PFK-1.1. PFK-1.1 condensates exhibit liquid-like properties, including spheroid shapes due to surface tension, fluidity due to deformations, and fast internal molecular rearrangements. Heterologous self-association domain cryptochrome 2 promotes formation of PFK-1.1 condensates and recruitment of aldolase/ALDO-1. PFK-1.1 condensates do not correspond to stress granules and might represent novel metabolic subcompartments. Our studies indicate that glycolytic protein PFK-1.1 can dynamically form condensates in vivo.     

Proteiniclasticum sediminis sp. nov., an obligate anaerobic bacterium isolated from anaerobic sludge

Antonie van Leeuwenhoek - An obligate anaerobic bacterial BAD-10 T was isolated from anaerobic acetochlor-degrading sludge. The strain was Gram-stain negative, curved rod-shaped,...     

喀什边境口岸陆运卡车及集装箱污染的新冠病毒基因特征分析

新疆维吾尔自治区喀什地区作为我国与中亚和欧洲的重要陆路货运口岸,来往货物运输频繁,引入新型冠状病毒(SARS-CoV-2)风险大,对我国新型冠状病毒肺炎(COVID-19)疫情防控造成压力.2020年11月我国新疆维吾尔自治区喀什地区发生输入SARS-CoV-2导致的本土聚集性COVID-19疫情.为明确货物运输载体携带SARS-CoV-2的基因特征以及边境快速物流系统作为SARS-CoV-2传播载体的可能性,本研究对2020年11月6日-2020年11月10日期间在喀什边境口岸货运卡车及运输的集装箱采集的35份SARS-CoV-2核酸阳性样本进行SARS-CoV-2全基因组序列测定和比对分析.结果 显示,35份样本ORFlab基因Ct值的中位数(最小值～最大值)为37.64(28.91～39.81),N基因Ct值的中位数(最小值～最大值)为36.50(26.35～39.30),Reads数匹配率的中位数(最小值～最大值)为51.95％(0.86％～99.31％),病毒载量较低;35份样本中基因组覆盖度达到70％以上的共计18份.基于Pango命名法,18条SARS-CoV-2基因组序列分别属于B.1、B.1.1、B.1.9、B.1.1.220、B.1.153和B.1.465共6个不同的基因型,其中3个基因型(B.1、B.1.1和B.1.153)在喀什边境接壤或邻近的四个国家同期采集的病例样本中也有发现.核苷酸突变位点和系统进化树分析显示,同一个地点采集的样本病毒基因组相似程度高;18条序列中的4条与喀什COVID-19疫情毒株代表序列处在同一个进化分支;其中1条序列与喀什COVID-19疫情毒株基因组存在1个或2个核苷酸突变位点差异,高度同源.本研究证实喀什COVID-19疫情期间边境货运卡车和集装箱存在境外多种基因型病毒的污染,其中存在喀什COVID-19疫情毒株的祖父代病毒,高度提示边境快速物流系统卡车及集装箱作为载体携带SARS-CoV-2病毒入境造成了本土疫情,这些数据为我国边境口岸地区的新冠防控策略制定及后续疫情溯源提供了关键的参考依据.     

呼吸道合胞病毒IgM抗体AlphaLISA快速检测方法的建立

呼吸道合胞病毒(Respiratory syncytial virus,RSV)属于副粘液病毒科,是一种下呼吸道感染最主要的RNA病毒.呼吸道合胞病毒感染是引起全球婴幼儿高致死率的呼吸道感染病原,仅次于疟疾,但用于检测RSV感染的选择相对较少.本文通过抗原抗体结合原理,建立呼吸道合胞病毒(RSV)IgM抗体AlphaLISA快速检测方法.小鼠抗人IgM单克隆抗体偶联的受体微球与临床血清样品中RSV特异性IgM抗体结合,RSV特异性IgM抗体再与生物素标记的RSV抗原结合,生物素连接偶联链霉亲和素的供体微球;受体微球和供体微球的距离被拉近小于200nm,680nm荧光激发供体微球生成单线态氧,扩散给受体微球,发射波长为520～620nm的荧光,荧光强度与血清中RSV特异性IgM抗体呈正比.结果显示,该方法批内变异系数与批间变异系数均小于10％,不与其他呼吸道病原体发生交叉反应,与间接免疫荧光法具有较好的一致性,总符合率达83.33％.该方法具有微量检测、快速省时、操作简便等优势,可快速检测RSV的IgM抗体,为早期确诊RSV感染提供高效可行方案.     

SHED aggregate exosomes shuttled miR‐26a promote angiogenesis in pulp regeneration via TGF‐β/SMAD2/3 signalling

ObjectivesPulp regeneration brings big challenges for clinicians, and vascularization is considered as its determining factor. We previously accomplished pulp regeneration with autologous stem cells from deciduous teeth (SHED) aggregates implantation in teenager patients, however, the underlying mechanism needs to be clarified for regenerating pulp in adults. Serving as an important effector of mesenchymal stem cells (MSCs), exosomes have been reported to promote angiogenesis and tissue regeneration effectively. Here, we aimed to investigate the role of SHED aggregate‐derived exosomes (SA‐Exo) in the angiogenesis of pulp regeneration.Materials and MethodsWe extracted exosomes from SHED aggregates and utilized them in the pulp regeneration animal model. The pro‐angiogenetic effects of SA‐Exo on SHED and human umbilical vein endothelial cells (HUVECs) were evaluated. The related mechanisms were further investigated.ResultsWe firstly found that SA‐Exo significantly improved pulp tissue regeneration and angiogenesis in vivo. Next, we found that SA‐Exo promoted SHED endothelial differentiation and enhanced the angiogenic ability of HUVECs, as indicated by the in vitro tube formation assay. Mechanistically, miR‐26a, which is enriched in SA‐Exo, improved angiogenesis both in SHED and HUVECs via regulating TGF‐β/SMAD2/3 signalling.ConclusionsIn summary, these data reveal that SA‐Exo shuttled miR‐26a promotes angiogenesis via TGF‐β/SMAD2/3 signalling contributing to SHED aggregate‐based pulp tissue regeneration. These novel insights into SA‐Exo may facilitate the development of new strategies for pulp regeneration.