用体外免疫法建立人—人抗流行性乙型脑炎病毒杂交瘤细胞株

利用单克隆抗体(McAb)进行病毒病的治疗是人们所关心的一个重大课题。 流行性乙型脑炎(乙脑)是一种严重威胁人民健康的急性传染病,病死率高,后遗症严重。国内外目前尚无特效疗法。陈伯权等用乙脑病毒皮下或腹腔感染3周龄小白鼠24、48小时及5天后,分别用乙脑病毒51-8McAb进行治疗,平均治愈率分别为78％、73％及22％。     

Single-cell transcriptomic atlas of primate cardiopulmonary aging

Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Diseas...     

Breast cancer-derived K172N,D301V mutations abolish Na/H exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling

Na⁺/H⁺ exchanger regulatory factor 1 (NHERF1) is a scaffold protein known to interact with a number of cancer-related proteins. nherf1 Mutations (K172N and D301V) were recently identified in breast cancer cells. To investigate the functional properties of NHERF1, wild-type and cancer-derived nherf1 mutations were stably expressed in SKMES-1 cells respectively. NHERF1-wt overexpression suppressed the cellular malignant phenotypes, including proliferation, migration, and invasion. nherf1 Mutations (K172N and D301V) caused complete or partial loss of NHERF1 functions by affecting the PTEN/NHERF1/PDGFRβ complex formation, inactivating NHERF1 inhibition of PDGF-induced AKT and ERK activation, and attenuating the tumor-suppressor effects of NHERF1-wt. These results further demonstrated the functional consequences of breast cancer-derived nherf1 mutations (K172N and D301V), and suggested the causal role of NHERF1 in tumor development and progression.     

Large-Area,Low-Cost Infrared Metamaterial Fabrication Via Pulsed Laser Deposition with Metallic Mesh as a Shadow Mask

Metamaterials are artificial periodic structures with negative permittivity and permeability. Several interesting properties can be obtained in metamaterials, such as negative index behavior, which can be used for building perfect lenses, cloaking, antennas, etc. As the metamaterial’s properties are determined by its structure, the key challenge is to reduce the fabrication cost of the periodic structure on the micrometer or nanometer scale for realistic applications. In this paper, we experimentally demonstrate a new one-step method for the fabrication of a large-area infrared metamaterial at extremely low cost. A metallic mesh is used as a shadow mask during the pulsed laser deposition (PLD) process to fabricate a FeNi/SiC/FeNi multilayer sandwich structure on Si substrate (cm² level). The sample shows a strong absorption peak in the infrared frequency range, and the absorption intensity changes with the sample’s geometry.     

Analysis of the Putative Role of CR1 in Alzheimer’s Disease: Genetic Association,Expression and Function

Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer’s disease (AD). Recent large genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the C3b/C4b receptor (CR1 or CD35) that are associated with late onset AD. Here, anti-CR1 antibodies (Abs) directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1) regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved.     

Aneuploid embryonic stem cells exhibit impaired differentiation and increased neoplastic potential

Aneuploidy leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem (ES) cells by generating a series of cell lines that each carries an extra copy of single chromosomes, including trisomy 6, 8, 11, 12, or 15. Most of these aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self‐renewal and showed a reduced capacity to differentiate in vitro. Moreover, trisomic stem cells formed teratomas more efficiently, from which undifferentiated cells can be recovered. Further investigations demonstrated that co‐culture of wild‐type and aneuploid ES cells or supplementation with extracellular BMP4 rescues the differentiation defects of aneuploid ES cells.     

Small interfering RNA targeting NF-κB attenuates lipopolysaccharide-induced acute lung injury in rats

Background

Veterinary cardiology, especially electrocardiography, has shown major advancements for all animal species. Consequently, the number of ovine species used as experimental animals has increased to date. Few studies have been published on ovine systematic electrocardiography, particularly with respect to lamb physiology and neonatology. This study aimed to standardize the values of normal waves, complexes, and intervals of the electrocardiogram (ECG) in clinically Bergamasca healthy neonatal lambs, used as experimental animals. Serial computerized electrocardiography was performed in 10 male and 12 female neonates on the 1st, 7th, 14th, 21st, 28th, and 35th days of age. The following parameters were analyzed: heart rate and rhythm, duration and amplitude of waves, duration of intervals, and heart electrical axis.

Results

During the first 35 days of life, (1) the sinusal heart rhythm was predominant, (2) there was a progressive decrease in the heart rate and R and T wave amplitude, and (3) a progressive increase in the PR, QT, and RR intervals. Finally, we confirmed that various components of neonatal evolution were more discernible in the augmented unipolar leads (aVF), which we recommend should be preferentially used in future studies. No significant statistical alterations were observed between males and females in relation to the analyzed parameters.

Conclusions

The information assimilated in this study is anticipated to enhance the diagnosis of multiple congenital heart defects in Bergamasca lambs and could be implemented in studies that use ovine species as experimental models.

     

Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation.However,the underlying cellular and molecular mechanisms remain unidentified.Here,we generated non-integrative induced pluripotent stem cells(iPSCs)from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation(c.3226C>T,p.R1076C).Vascular smooth muscle cells(VSMCs)differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes,including activation of the NOTCH and NF-kB signaling pathway,cytoskeleton disorganization,and excessive cell proliferation.In comparison,these abnormalities were not observed in vascular endothelial cells(VECs)derived from the patients iPSCs.Importantly,the abnormal upregulation of NF-kB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor,providing a potential therapeutic strategy for CADASIL.Overall,using this iPSCbased disease model,our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease.     

三种园林植物对夜间光照的响应与适应特征

光污染是城市生态系统中重要的污染类型,目前的研究集中在光污染对人类健康、昆虫生活史、生活习性、活动规律等方面,对植物生理生态的效应研究则较少。以凤仙花(Impatiens balsamina)、小叶栀子(Gardenia jasminoides)、夏菊(Dendranthema morifolium)为研究对象,研究白光LED灯从每天18:00—24:00照光(T1处理)、每天18:00—次日8:00照光(T2处理)以及自然光周期(CK)等3种光环境条件下,3种植物生物量积累与分配、开花特征、色素含量、碳氮含量及其比值(C/N比)、抗氧化酶等方面的响应与适应特征。结果表明,T1和T2处理增加了凤仙花的生物量(分别为CK的1.4和1.9倍),降低了叶片和茎的N含量,增加了叶片的C/N比(分别为CK的1.2和1.9倍),降低了叶片的色素含量;T1处理延迟了凤仙花的花期,T2处理条件下凤仙花不开花。T1和T2处理虽然没有影响小叶栀子的花期,但增加了花的数量,减小了花的平均重量,花的C/N比显著增加(T2处理为CK的1.3倍);T2处理降低了小叶栀子叶片的叶绿素a、b及总叶绿素含量,增加了丙二醛的含量(T2处理为CK的1.7倍)。夏菊的生物量及生理特征受到T1和T2处理的影响最小,但T1和T2处理均抑制了夏菊开花。这些结果表明凤仙花和夏菊开花对光污染引起光周期的变化比较敏感,凤仙花的生长和养分特征也受到夜间光照的显著影响,光污染对小叶栀子的叶片造成了显著伤害。总的来讲,与T2相比,T1处理对3种植物的负面影响较小,在城市照明的管理过程中,可以根据需要缩短夜间光照的时间,既可以节约能源,又可以减小对植物生理生态的负面影响。