Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment

Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.Subject terms: Cognitive neuroscience, Alzheimer''s disease, Cellular neuroscience     

A Five-Year Prospective Study of Diabetic Retinopathy Progression in Chinese Type 2 Diabetes Patients with “Well-Controlled” Blood Glucose

Purpose

To determine the progression rate and risk factors for diabetic retinopathy (DR) in Chinese type 2 diabetic patients who have reached the target hemoglobin A1c (HbA1c) level recommended by the American Diabetes Association.

Methods

This was a 5-year community-based prospective study. The study population consisted of patients with type 2 diabetes with HbA1c less than 7.0%. Demographic information, systemic examination results and ophthalmological test results for each participant were collected. The outcome of this study was the progression of DR, which was defined as an increase in DR grade in one or both eyes at the final visit in comparison to the baseline status. The association between each potential risk factor and DR progression was studied.

Results

A total of 453 patients with HbA1c less than 7.0% were included in the study group. In 146 patients (32.22%), DR developed or progressed during the five-year follow-up. Baseline HbA1c level was the only independent risk factor for DR progression (p<0.01, OR = 2.84, 95%CI: 2.11~3.82). The logistic regression function suggested that the possibility of DR progression increased fastest when baseline HbA1c increased from 5.2% to 6.4%. The 5-year DR progression rate in patients with baseline HbA1c less than 5.2%, between 5.2% and 6.4%, and over 6.4% were 19.62%, 24.41%, and 76.83%, respectively.

Conclusions

To slow the progression of DR in Chinese patients with type 2 diabetes, more intensive glucose control is recommended.     

天童山森林土壤种子库的时空格局

土壤种子库是植物群落的潜在物种库。在中国东部典型丘陵地区天童国家森林公园内选取8类微地形, 分别于2008年9月、12月和2009年3月、6月进行野外调查取样和室内实验, 从总计1,960份土样中挑选种子进行鉴定及分类统计, 研究其时空格局, 探讨自然森林土壤种子库的基本特征及分布规律。结果显示: (1)共检出有活力的种子5,024粒, 共鉴定出68个种, 其中定名种65个; 落叶阔叶乔木和常绿阔叶小乔木物种数量以及种子数量均占优势; 土壤种子库与地上植被共有种为48种, 相似性系数为0.45。(2) 2级和3级顶坡及下部边坡、麓坡、泛滥性阶地种子库储量较大, 而高上部边坡、中上部边坡和低上部边坡种子库储量较小。雷公鹅耳枥(Carpinus viminea)和细枝柃(Eurya loquaiana)是各个微地形单元种子库的优势种。其他优势种中, 上部坡面的微地形主要为格药柃(E. muricata)、短梗冬青(Ilex buergeri)、黑山山矾(Symplocos heishanensis)、四川山矾(S. setchuensis)等常绿树种, 而下部坡面的微地形主要为南酸枣(Choerospondias axillaris)、橄榄槭(Acer olivaceum)、西川朴(Celtis vandervoetiana)等落叶树种。(3)土壤种子库储量在垂直空间上的分布是0-2 cm土层>2-5 cm土层>5-10 cm土层>枯枝落叶层。(4)土壤种子库具有明显的季节动态, 其储量在各个取样时间中的分布为12月>3月>9月>6月。     

绿色基础设施供需适配关系演进特征及其规律——以南京市为例

绿色基础设施（GI）供需均衡对维护城市或区域生态系统稳定,提升国土空间治理体系和治理能力现代化水平,推动城市高质量发展具有重要意义。从绿色基础设施供需适配关系的视角出发,运用生态系统服务价值法对GI服务供给进行测度,从社会、经济、生态和环境四方面综合评价GI需求,研究南京市GI供需适配关系的演进情势,揭示其时空配置的差异性。结果表明：（1）2000-2020年,南京市GI供给呈主城低、郊区高的分布格局,总供给、人均供给和单项供给均先减后增。（2）GI总需求逐年减少,形成从中心城区向郊区递减的三个圈层。（3）南京市共划出9个供需适配类型,对应11个辖区划出99个供需适配类型组合区,供需适配较好区与较差区分别占全市国土面积的26%和44%,呈不均衡分布。（4）主城区较适应的匹配类型是低供给-中需求,郊区维持低供给-低需求较符合区域发展实际,并针对不同类型区优化提升提出对策建议。     

单增李斯特菌毒力因子溶血素关键氨基酸位点在感染过程中的作用研究

【目的】探究单增李斯特菌溶血素O (listeriolysin O, LLO)中D3区域β8折叠片上第253位氨基酸(谷氨酰胺,Q)和第254位氨基酸(异亮氨酸,I)对单增李斯特菌(Listeria monocytogenes)感染生物学功能的影响。【方法】构建LLO_Q253A和LLO_I254A突变蛋白的原核表达菌株,以及利用同源重组方法构建hly_Q253A和hly_I254A突变株;通过表达纯化突变蛋白,测定溶血活性;比较LLO第253位Q和第254位I均突变成丙氨酸(A)后,对细菌体外生长能力、黏附侵袭、胞内迁移和增殖能力的影响。【结果】相应位点突变后,LLO蛋白均能够正常表达。在pH 6.5条件下,所有突变蛋白和突变株的溶血活性丧失。然而,在pH 5.5条件下,LLO_I254A和hly_I254A恢复了溶血活性。与野生株相比,突变株的体外生长、黏附能力和胞内增殖能力均无明显差异;突变株的侵袭能力和胞间迁移能力显著低于野生株。【结论】本研究证实第253位Q和第254位I均突变成A后,单增李斯特菌在pH 6.5条件下丧失溶血活性,并降低了感染宿主细胞的能力,但具体机制还有待进一步探索。本研究为深入探究LLO结构对单增李斯特菌生物学功能的影响奠定基础,对单增李斯特菌点突变株的构建具有一定参考意义。     

Genome-Wide Identification and Characterization of Germin and Germin-Like Proteins (GLPs) and Their Response Under Powdery Mildew Stress in Wheat (Triticum aestivum L.)

Plant Molecular Biology Reporter - Germin and germin-like proteins (GLPs) play multifaceted roles in plants and participate in signaling processes associated with host–pathogen interactions...     

Salidroside-pretreated mesenchymal stem cells contribute to neuroprotection in cerebral ischemic injury in vitro and in vivo

Journal of Molecular Histology - Mesenchymal stem cells (MSCs) are considered a promising tool for treating cerebral ischemic injury. However, their poor survival after transplantation limits their...     

上海市某三甲医院幽门螺杆菌耐药性和毒力与其生物膜形成能力的相关性研究

为探讨复旦大学附属华东医院(以下简称本院)分离培养的幽门螺杆菌(Helicobacter pylori,H. pylori)的耐药性、毒力和感染特征与其生物膜形成能力的相关性,收集2014年12月-2015年6月于本院消化内镜中心的胃活检组织标本及相应临床病例资料,分离培养获得幽门螺杆菌,分析菌株的耐药性、毒力基因型、临床病例特征。结果显示,从胃活检组织样本中共分离培养28株幽门螺杆菌,对左氧氟沙星(levofloxacin,LEV)、甲硝唑(metronidazole,MTZ)和克拉霉素(clarithromycin,CLA)的耐药率分别为32%、75%和11%,未发现阿莫西林(amoxicillin,AMX)耐药。单一药物耐药17株(17/28,61%),双重耐药10株(10/28,36%)。毒力基因cagA、oipA和vacAs1检出率为100%,未检出vacAs2。基因型vacAs1m1占39%(11/28),vacAs1m2占61%(17/28);iceA1占54%(15/28),iceA2占21%(6/28),iceA1A2占25%(7/28);dupA^＋占36%(10/28)。28株菌株均能形成生物膜,但能力不尽相同。单因素及独立样本t检验分析显示,45～59岁、iceA1^＋dupA^－基因型和甲硝唑敏感菌株形成生物膜的能力较强。结果提示,本院分离的幽门螺杆菌对甲硝唑耐药率最高,双重耐药不容忽视。菌株主要毒力基因型为cagA、oipA、vacAs1m2。幽门螺杆菌的生物膜形成能力与患者年龄有关,45～59岁组较强;携带毒力基因iceA1的菌株生物膜形成能力强;dupA基因型及甲硝唑耐药与菌株生物膜形成呈负相关。