MicroRNA-340-5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice

Alzheimer′s disease (AD) is a chronic neurodegenerative disorder which is the primary cause of dementia in the elderly. Telomere attrition has been proposed as a hallmark of aging. Our study aimed to explore the mechanism of the protection of telomere 1 (POT1) in regulating telomere length and affecting cellular senescence in AD. The AD mouse model was established by d -galactose and aluminum chloride, and the water maze test and dark avoidance test were used to detect the behaviors of mice and confirm the success of AD mouse model. AD cell model was established with HT22 cells induced by Aβ₄₂ oligomers. POT1 expression in the AD model was detected by quantitative real-time polymerase chain reaction. Cellular telomere length in hippocampal tissue was analyzed by telomere restriction fragment. Localization of intracellular POT1, telomerase, and telomeres was analyzed by immunofluorescence and fluorescence in situ hybridization. Dual-luciferase assay was used to validate the targeted binding relationship between microRNA-340-5p (miR-340-5p) and POT1. After inhibiting POT1 expression, the symptoms of AD in mice were improved. Aβ_1–42 deposition was reduced, whereas telomere length and telomerase activity was increased. Dual-luciferase assay verified the binding relationship between miR-340-5p and POT1. An increase in miR-340-5p expression could alleviate cellular senescence and AD symptoms. miR-340-5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms. This study made a conclusion that miR-340-5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms in mice.     

CT定量分析在冠心病介入治疗前后血流灌注改变的评估价值

摘要 目的：探讨CT定量分析在冠心病介入治疗前后血流灌注改变的评估价值。方法：2018年2月到2020年11月选择在本院诊治的冠心病患者95例作为研究对象,所有患者都给予经皮冠状动脉介入治疗,在介入前1 d与介入后1个月进行CT定量与超声检查,随访介入后6个月的冠状动脉再狭窄情况并进行相关性分析。结果：所有患者都顺利完成介入治疗,介入期无严重并发症发生。95例患者介入后1个月的左室射血分数(ejectionfraction,EF)、左室短轴缩短率(fractionalshortening,FS)高于介入前1 d(P<0.05),介入前后左室等容舒张时间(iso-volumicrelaxationtime,IVRT)对比差异无统计学意义(P>0.05)。95例患者介入后1个月的心肌血流量(Myocardialbloodflow,MBF)、心肌血容量(Myocardialbloodvolume,MBV)高于介入前1d(P<0.05),达峰时间(Timetopeak,TTP)低于介入前1 d(P<0.05)。介入后随访6个月,冠状动脉再狭窄14例,再狭窄率14.7 %,其中中度狭窄12例,重度狭窄2例;Pearson分析显示冠心病患者介入前1 d的MBF、MBV、TTP与FS、EF都存在相关性(P<0.05);Logistic回归分析显示MBF、MBV、TTP、FS、EF为影响冠心病患者介入后随访再狭窄率的重要因素(P<0.05)。结论：CT定量分析在冠心病介入前后的应用能有效反映血流灌注改变情况,且与患者的心功能存在相关性,也可有效预测患者介入随访冠状动脉再狭窄发生情况。     

H3K4 di-methylation governs smooth muscle lineage identity and promotes vascular homeostasis by restraining plasticity

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Sustainability of SARS-CoV-2 Induced Humoral Immune Responses in COVID-19 Patients from Hospitalization to Convalescence Over Six Months

Virologica Sinica - Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection, the protection period...     

The dynamics of sexual contact networks: effects on disease spread and control

Sexually transmitted pathogens persist in populations despite the availability of biomedical interventions and knowledge of behavioural changes that would reduce individual-level risk. While behavioural risk factors are shared between many sexually transmitted infections, the prevalence of these diseases across different risk groups varies. Understanding this heterogeneity and identifying better control strategies depends on an improved understanding of the complex social contact networks over which pathogens spread. To date, most efforts to study the impact of sexual network structure on disease dynamics have focused on static networks. However, the interaction between the dynamics of partnership formation and dissolution and the dynamics of transmission plays a role, both in restricting the effective network accessible to the pathogen, and in modulating the transmission dynamics. We present a simple method to simulate dynamical networks of sexual partnerships. We inform the model using survey data on sexual attitudes and lifestyles, and investigate how the duration of infectiousness changes the effective contact network over which disease may spread. We then simulate several control strategies: screening, vaccination and behavioural interventions. Previous theory and research has advanced the importance of core groups for spread and control of STD. Our work is consistent with the importance of core groups, but extends this idea to consider how the duration of infectiousness associated with a particular pathogen interacts with host behaviours to define these high risk subpopulations. Characteristics of the parts of the network accessible to the pathogen, which represent the network structure of sexual contacts from the “point of view” of the pathogen, are substantially different from those of the network as a whole. The pathogen itself plays an important role in determining this effective network structure; specifically, we find that if the pathogen’s duration of infectiousness is short, infection is more concentrated in high-activity, high-concurrency individuals even when all other factors are held constant. Widespread screening programmes would be enhanced by follow-up interventions targeting higher-risk individuals, because screening shortens the expected duration of infectiousness and causes a greater relative decrease in prevalence among lower-activity than in higher-activity individuals. Even for pathogens with longer durations of infectiousness, our findings suggest that targeting vaccination and behavioural interventions towards high-activity individuals provides comparable benefits to population-wide interventions.     

Association of the ACE-II genotype with the risk of nephrotic syndrome in Pakistani children

Nephrotic syndrome is a common pediatric glomerular disease associated with heavy proteinuria. Since, the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is a putative genetic risk factor for NS, in this study, ACE (I/D) polymorphism was analyzed in 268 NS and 223 control samples by a PCR-based method. The genotypic and allelic frequencies were determined and the association between ACE I/D polymorphism and NS was evaluated. The frequency distribution of the II, ID and DD genotypes was 82 (30.6%), 128 (47.8%) and 58 (21.6%) in the NS patients and 9 (4.0%), 171 (76.7%) and 43 (19.3%) in the control samples respectively. In the Pakistani pediatric NS population, the II genotypic and allelic frequencies were found to be significantly associated with the disease (OR = 6.755; C.I = 3-14.9). No significant association was found between this polymorphism and the response to standard steroid therapy. Thus, in contrast to reports from other parts of the world, the II genotype was found to be significantly associated with NS in the Indian and Malay populations and in the Pakistani population described here. To our knowledge, this is the first report from Pakistan describing the association of the ACE I/D polymorphism with pediatric NS. On the basis of these results, it is suggested that analysis of the ACE (I/D) polymorphism should be performed for the early diagnosis in the high risk NS patients in South Asia.     

梨种质资源对黑星病抗性评价

采用人工接种黑星病菌的方法,对国家果树种质兴城梨资源圃保存的197份梨种质资源进行了抗病性鉴定,结果表明:不同梨种类发病率差异很大,其中白梨和砂梨最易感病,秋子梨和种间杂交选育品种较易感病,新疆梨较抗病,西洋梨最抗病;对病情指数在各梨种类分布进行了分析;在白梨、砂梨、秋子等各系统分别筛选出黄鸡腿、甩梨、酸梨、锦香等一批抗病资源;对田间自然感病与人工接种感病结果进行了比较。     

Molecular Paths Linking Metabolic Diseases,Gut Microbiota Dysbiosis and Enterobacteria Infections

Alterations of both ecology and functions of gut microbiota are conspicuous traits of several inflammatory pathologies, notably metabolic diseases such as obesity and type 2 diabetes. Moreover, the proliferation of enterobacteria, subdominant members of the intestinal microbial ecosystem, has been shown to be favored by Western diet, the strongest inducer of both metabolic diseases and gut microbiota dysbiosis. The inner interdependence between the host and the gut microbiota is based on a plethora of molecular mechanisms by which host and intestinal microbes modify each other. Among these mechanisms are as follows: (i) the well-known metabolic impact of short chain fatty acids, produced by microbial fermentation of complex carbohydrates from plants; (ii) a mutual modulation of miRNAs expression, both on the eukaryotic (host) and prokaryotic (gut microbes) side; (iii) the production by enterobacteria of virulence factors such as the genotoxin colibactin, shown to alter the integrity of host genome and induce a senescence-like phenotype in vitro; (iv) the microbial excretion of outer-membrane vesicles, which, in addition to other functions, may act as a carrier for multiple molecules such as toxins to be delivered to target cells. In this review, I describe the major molecular mechanisms by which gut microbes exert their metabolic impact at a multi-organ level (the gut barrier being in the front line) and support the emerging triad of metabolic diseases, gut microbiota dysbiosis and enterobacteria infections.     

实时三维超声输卵管造影与X线造影诊断不孕症患者输卵管病变的价值比较

目的:比较实时三维超声输卵管造影与X线造影检查诊断女性不孕症患者输卵管病变的临床应用价值。方法:选择2014年3月至2016年12月我院诊治的不孕症患者60例作为研究对象,所有患者都于月经干净后3-7 d同时随机实施实时三维超声输卵管造影与X线造影检查,观察并记录造影图像质量与诊断结果,比较两种方法的诊断效果。结果:实时三维超声输卵管造影与X线造影的图像质量优良率分别为98.3%和86.7%,实时三维超声输卵管造影的图像质量明显高于X线造影(P0.05)。实时三维超声输卵管造影与X线造影诊断不孕症患者输卵管不通畅率分别为56.7%和46.7%,实时三维超声输卵管造影组显著高于X线造影组(P0.05)。输卵管通畅性评价金标准腹腔镜下通液术诊断发现输卵管不通畅35例,在此基础上实时三维超声输卵管造影与X线造影检查不孕症的敏感性分别为97.1%和80.0%,特异性均为100.0%,超声诊断的敏感性明显高于X线(P0.05)。结论:相对于X线造影,实时三维超声输卵管造影检查不孕症患者输卵管病变的图像质量更好,有利于疾病的判断,对输卵管通畅度判断更精确,利于后期治疗及疾病预防,还可提高诊断敏感性。